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Gardasil 9 at 10 Years: Vaccine Protects Against Multiple Cancers
Vaccination against human papilloma virus (HPV), a group of more than 200 viruses infecting at least 50% of sexually active people over their lifetimes, has proved more than 90% effective for preventing several diseases caused by high-risk HPV types.
Gardasil 4: 2006
It started in 2006 with the approval of Human Papillomavirus Quadrivalent, types 6, 11, 16, and 18 (Gardasil 4). Merck’s vaccine began to lower rates of cervical cancer, a major global killer of women.
“It’s fair to say the vaccine has been an American and a global public health success story in reducing rates of cervical cancer,” Paula M. Cuccaro, PhD, assistant professor of health promotion and behavioral sciences at University of Texas School of Public Health, Houston, said in an interview.
How does a common virus trigger such a lethal gynecologic malignancy? “It knocks out two important cancer suppressor genes in cells,” explained Christina Annunziata,MD, PhD, a medical oncologist and senior vice president of extramural discovery science for the American Cancer Society. HPV oncoproteins are encoded by the E6 and E7 genes. As in other DNA tumor viruses, the E6 and E7 proteins functionally inactivate the tumor suppressor proteins p53 and pRB, respectively.
US Prevalence
Despite screening and vaccination, cervical cancer is still very much around. This year, 13,820 new cases of invasive cervical cancer will be diagnosed in the United States, and approximately 4360 women will die of it, according to the American Cancer Society. Even before the advent of Gardasil 4, incidence rates had already decreased by more than half from the mid-1970s to the mid-2000s, thanks largely to Pap smear screening programs for treatable premalignant lesions. “The US rate had dropped to about 20 per 100,000 women even before Gardasil 4,” said Annunziata. “After the introduction of the first vaccine, it decreased to 7 per 100,000, a decrease of about 30%, but it remains plateaued now at about the same level.”
Although the past decade has seen rates generally stabilize, there have been some changes in different age groups. In women ages 30-44, rates increased 1.7% each year from 2012 to 2019, while rates declined 11% each year for women ages 20-24— probably reflecting the impact of the first wave of prevention from Gardasil 4.
In one 2021 population-based study of US cancer registry data from 1999 to 2017, rates of both cervical squamous cell carcinoma and adenocarcinoma dropped. The largest declines occurred in females 15-20 years old, the age group most likely to be vaccinated against HPV but not typically screened, suggesting a vaccine-related effect.
Gardasil 9: 2014
With the 2014 approval of the vaccine’s second iteration, Gardasil 9, which replaced Gardasil 4 and targeted 9 HPV strains, immunization has taken broader aim. The strains covered by Gardasil 9 protect against oropharyngeal and other head and neck cancers — as well as penile, anal, vulvar, and vaginal malignancies and premalignancies, and genital warts in both sexes ages 9-45.
It may be years, however, before the impact of the newer polyvalent formulation is felt. “While the first vaccine has been successful against the prevalent strains of HPV linked to cervical cancer, it’s a little early to call it for the newer vaccine since oropharyngeal cancers tend to develop later in older men,” Cuccaro said. “But the types of HPV linked to mouth and throat cancers and covered by the newer vaccines are much less prevalent in those who are vaccinated. The strains not covered in the vaccine you see are equally present in the vaccinated and non-vaccinated.”
Angela L. Myers, MD, MPH, division director of infectious diseases and medical director of the Center for Wellbeing at Children’s Mercy in Kansas City, Missouri, added, “Unlike for cervical cancer, there are no screening programs for oropharyngeal lesions, so you have to wait to see rates until actual cancer develops.”
A 2023 review reported that HPV vaccination reduced levels of oropharyngeal HPV positivity in men, strengthening the case for pangender immunization.
And in a recent phase 3 doubled-blind trial, GARDASIL 9 reduced the incidence of anogenital persistent infection caused by nine types of HPV compared with a placebo.
Increasing Uptake
The current public health aim is to have 80% of young people in the targeted age group vaccinated with two doses. Today, uptake among those 9-26 years old stands at about 78% of girls and 75% of boys for the first dose, said Annunziata. “But it’s only about 61% for the two doses in the current series, and we want to improve that.”
Some parents may still harbor fears that immunizing teens and tweens — both the American Academy of Pediatrics and the American Cancer Society recommend immunization at age 9 — will open the door to precocious sexual activity.
“But overall, uptake in tweens and young teens has increased because the messaging has changed,” said Myers, with the rationale now focusing on cancer prevention not sexual-infection prophylaxis. “This is similar to the hepatitis B vaccine, which used to be given to young adults and is now given to newborns to prevent cancer.”
Cuccaro added that a proactive presentation by healthcare professionals has a significant effect on vaccine uptake and increases the odds of vaccination ninefold. “Providers should take a presumptive approach and avoid just offering the vaccine as an option. It should be included with regular childhood vaccinations,” she said. “And the advantage of starting early at age 9 is that you can spread the doses out across other regular childhood vaccinations, whereas if you start at age 11, you need to add the HPV vaccine to three other vaccines that are given at that time.”
After age 15, three doses are necessary. “Providers should stress to parents that it’s most effective when given before young people become sexually active and exposed to HPV,” Cuccaro said. And Myers stressed that despite the vaccine’s effectiveness, routine screening for cervical premalignancies is still important.
Despite increasing coverage, vaccination rates have some distance to go before the public health target of at least 80% uptake of the series in the targeted age group, Cuccaro cautioned.
On the global stage, barriers to immunization remain, but the World Health Organization has endorsed a campaign to eradicate cervical cancer through HPV vaccination. It has predicted that the 21st century may be the last to experience HPV-associated cancers, currently responsible for more than 300,000 annual deaths worldwide.
A Brief History of HPV Vaccines
- 1951. Cervical cancer patient Henrietta Lacks’ rapidly dividing cervical cells are collected by George Otto Gey at Johns Hopkins Hospital. They create the first immortal cell line (HeLa) used to study cancers and vaccines worldwide.
- 1976. Harald zur Hausen suggests that genital wart-associated HPV, not herpes simplex, is the probable cause of cervical cancer.
- 1983. HPV is confirmed as a cause of cancer.
- 1991. The first HPV vaccine is developed.
- 2002. Proof of principle and protective efficacy for the monovalent HPV 16 are shown.
- 2006. Merck’s Gardasil 4 (HPV 4) is FDA approved in girls ages 9-26 for protection against strains 6, 11, 16, and 18 — the cause of more than 70% of cervical cancer cases.
- 2009. Approval of Gardasil 4 is expanded to boys ages 9-26 for the prevention of genital warts.
- 2009. The FDA approves GlaxoSmithKline’s Cervarix (HPV 16 and 18) for girls and young women. The vaccine was withdrawn from the US market in 2016 following the success of Gardasil 9 but is used abroad for HPV cancer prevention.
- 2014. The 9-valent recombinant vaccine Gardasil 9 is FDA approved for protection against several low-risk, wart-causing HPV strains as well as the high-risk cancer strains targeted by HPV 4.
- 2018. The FDA expands approval to include females and males 27-45 years old.
- 2020. The FDA extends approval of Gardasil 9 to include prevention not only of cervical cancer but also, vaginal, vulvar, anal, oropharyngeal, and other head and neck cancers.
Annunziata, Cuccaro, and Myers had no competing interests to declare.
A version of this article appeared on Medscape.com.
Vaccination against human papilloma virus (HPV), a group of more than 200 viruses infecting at least 50% of sexually active people over their lifetimes, has proved more than 90% effective for preventing several diseases caused by high-risk HPV types.
Gardasil 4: 2006
It started in 2006 with the approval of Human Papillomavirus Quadrivalent, types 6, 11, 16, and 18 (Gardasil 4). Merck’s vaccine began to lower rates of cervical cancer, a major global killer of women.
“It’s fair to say the vaccine has been an American and a global public health success story in reducing rates of cervical cancer,” Paula M. Cuccaro, PhD, assistant professor of health promotion and behavioral sciences at University of Texas School of Public Health, Houston, said in an interview.
How does a common virus trigger such a lethal gynecologic malignancy? “It knocks out two important cancer suppressor genes in cells,” explained Christina Annunziata,MD, PhD, a medical oncologist and senior vice president of extramural discovery science for the American Cancer Society. HPV oncoproteins are encoded by the E6 and E7 genes. As in other DNA tumor viruses, the E6 and E7 proteins functionally inactivate the tumor suppressor proteins p53 and pRB, respectively.
US Prevalence
Despite screening and vaccination, cervical cancer is still very much around. This year, 13,820 new cases of invasive cervical cancer will be diagnosed in the United States, and approximately 4360 women will die of it, according to the American Cancer Society. Even before the advent of Gardasil 4, incidence rates had already decreased by more than half from the mid-1970s to the mid-2000s, thanks largely to Pap smear screening programs for treatable premalignant lesions. “The US rate had dropped to about 20 per 100,000 women even before Gardasil 4,” said Annunziata. “After the introduction of the first vaccine, it decreased to 7 per 100,000, a decrease of about 30%, but it remains plateaued now at about the same level.”
Although the past decade has seen rates generally stabilize, there have been some changes in different age groups. In women ages 30-44, rates increased 1.7% each year from 2012 to 2019, while rates declined 11% each year for women ages 20-24— probably reflecting the impact of the first wave of prevention from Gardasil 4.
In one 2021 population-based study of US cancer registry data from 1999 to 2017, rates of both cervical squamous cell carcinoma and adenocarcinoma dropped. The largest declines occurred in females 15-20 years old, the age group most likely to be vaccinated against HPV but not typically screened, suggesting a vaccine-related effect.
Gardasil 9: 2014
With the 2014 approval of the vaccine’s second iteration, Gardasil 9, which replaced Gardasil 4 and targeted 9 HPV strains, immunization has taken broader aim. The strains covered by Gardasil 9 protect against oropharyngeal and other head and neck cancers — as well as penile, anal, vulvar, and vaginal malignancies and premalignancies, and genital warts in both sexes ages 9-45.
It may be years, however, before the impact of the newer polyvalent formulation is felt. “While the first vaccine has been successful against the prevalent strains of HPV linked to cervical cancer, it’s a little early to call it for the newer vaccine since oropharyngeal cancers tend to develop later in older men,” Cuccaro said. “But the types of HPV linked to mouth and throat cancers and covered by the newer vaccines are much less prevalent in those who are vaccinated. The strains not covered in the vaccine you see are equally present in the vaccinated and non-vaccinated.”
Angela L. Myers, MD, MPH, division director of infectious diseases and medical director of the Center for Wellbeing at Children’s Mercy in Kansas City, Missouri, added, “Unlike for cervical cancer, there are no screening programs for oropharyngeal lesions, so you have to wait to see rates until actual cancer develops.”
A 2023 review reported that HPV vaccination reduced levels of oropharyngeal HPV positivity in men, strengthening the case for pangender immunization.
And in a recent phase 3 doubled-blind trial, GARDASIL 9 reduced the incidence of anogenital persistent infection caused by nine types of HPV compared with a placebo.
Increasing Uptake
The current public health aim is to have 80% of young people in the targeted age group vaccinated with two doses. Today, uptake among those 9-26 years old stands at about 78% of girls and 75% of boys for the first dose, said Annunziata. “But it’s only about 61% for the two doses in the current series, and we want to improve that.”
Some parents may still harbor fears that immunizing teens and tweens — both the American Academy of Pediatrics and the American Cancer Society recommend immunization at age 9 — will open the door to precocious sexual activity.
“But overall, uptake in tweens and young teens has increased because the messaging has changed,” said Myers, with the rationale now focusing on cancer prevention not sexual-infection prophylaxis. “This is similar to the hepatitis B vaccine, which used to be given to young adults and is now given to newborns to prevent cancer.”
Cuccaro added that a proactive presentation by healthcare professionals has a significant effect on vaccine uptake and increases the odds of vaccination ninefold. “Providers should take a presumptive approach and avoid just offering the vaccine as an option. It should be included with regular childhood vaccinations,” she said. “And the advantage of starting early at age 9 is that you can spread the doses out across other regular childhood vaccinations, whereas if you start at age 11, you need to add the HPV vaccine to three other vaccines that are given at that time.”
After age 15, three doses are necessary. “Providers should stress to parents that it’s most effective when given before young people become sexually active and exposed to HPV,” Cuccaro said. And Myers stressed that despite the vaccine’s effectiveness, routine screening for cervical premalignancies is still important.
Despite increasing coverage, vaccination rates have some distance to go before the public health target of at least 80% uptake of the series in the targeted age group, Cuccaro cautioned.
On the global stage, barriers to immunization remain, but the World Health Organization has endorsed a campaign to eradicate cervical cancer through HPV vaccination. It has predicted that the 21st century may be the last to experience HPV-associated cancers, currently responsible for more than 300,000 annual deaths worldwide.
A Brief History of HPV Vaccines
- 1951. Cervical cancer patient Henrietta Lacks’ rapidly dividing cervical cells are collected by George Otto Gey at Johns Hopkins Hospital. They create the first immortal cell line (HeLa) used to study cancers and vaccines worldwide.
- 1976. Harald zur Hausen suggests that genital wart-associated HPV, not herpes simplex, is the probable cause of cervical cancer.
- 1983. HPV is confirmed as a cause of cancer.
- 1991. The first HPV vaccine is developed.
- 2002. Proof of principle and protective efficacy for the monovalent HPV 16 are shown.
- 2006. Merck’s Gardasil 4 (HPV 4) is FDA approved in girls ages 9-26 for protection against strains 6, 11, 16, and 18 — the cause of more than 70% of cervical cancer cases.
- 2009. Approval of Gardasil 4 is expanded to boys ages 9-26 for the prevention of genital warts.
- 2009. The FDA approves GlaxoSmithKline’s Cervarix (HPV 16 and 18) for girls and young women. The vaccine was withdrawn from the US market in 2016 following the success of Gardasil 9 but is used abroad for HPV cancer prevention.
- 2014. The 9-valent recombinant vaccine Gardasil 9 is FDA approved for protection against several low-risk, wart-causing HPV strains as well as the high-risk cancer strains targeted by HPV 4.
- 2018. The FDA expands approval to include females and males 27-45 years old.
- 2020. The FDA extends approval of Gardasil 9 to include prevention not only of cervical cancer but also, vaginal, vulvar, anal, oropharyngeal, and other head and neck cancers.
Annunziata, Cuccaro, and Myers had no competing interests to declare.
A version of this article appeared on Medscape.com.
Vaccination against human papilloma virus (HPV), a group of more than 200 viruses infecting at least 50% of sexually active people over their lifetimes, has proved more than 90% effective for preventing several diseases caused by high-risk HPV types.
Gardasil 4: 2006
It started in 2006 with the approval of Human Papillomavirus Quadrivalent, types 6, 11, 16, and 18 (Gardasil 4). Merck’s vaccine began to lower rates of cervical cancer, a major global killer of women.
“It’s fair to say the vaccine has been an American and a global public health success story in reducing rates of cervical cancer,” Paula M. Cuccaro, PhD, assistant professor of health promotion and behavioral sciences at University of Texas School of Public Health, Houston, said in an interview.
How does a common virus trigger such a lethal gynecologic malignancy? “It knocks out two important cancer suppressor genes in cells,” explained Christina Annunziata,MD, PhD, a medical oncologist and senior vice president of extramural discovery science for the American Cancer Society. HPV oncoproteins are encoded by the E6 and E7 genes. As in other DNA tumor viruses, the E6 and E7 proteins functionally inactivate the tumor suppressor proteins p53 and pRB, respectively.
US Prevalence
Despite screening and vaccination, cervical cancer is still very much around. This year, 13,820 new cases of invasive cervical cancer will be diagnosed in the United States, and approximately 4360 women will die of it, according to the American Cancer Society. Even before the advent of Gardasil 4, incidence rates had already decreased by more than half from the mid-1970s to the mid-2000s, thanks largely to Pap smear screening programs for treatable premalignant lesions. “The US rate had dropped to about 20 per 100,000 women even before Gardasil 4,” said Annunziata. “After the introduction of the first vaccine, it decreased to 7 per 100,000, a decrease of about 30%, but it remains plateaued now at about the same level.”
Although the past decade has seen rates generally stabilize, there have been some changes in different age groups. In women ages 30-44, rates increased 1.7% each year from 2012 to 2019, while rates declined 11% each year for women ages 20-24— probably reflecting the impact of the first wave of prevention from Gardasil 4.
In one 2021 population-based study of US cancer registry data from 1999 to 2017, rates of both cervical squamous cell carcinoma and adenocarcinoma dropped. The largest declines occurred in females 15-20 years old, the age group most likely to be vaccinated against HPV but not typically screened, suggesting a vaccine-related effect.
Gardasil 9: 2014
With the 2014 approval of the vaccine’s second iteration, Gardasil 9, which replaced Gardasil 4 and targeted 9 HPV strains, immunization has taken broader aim. The strains covered by Gardasil 9 protect against oropharyngeal and other head and neck cancers — as well as penile, anal, vulvar, and vaginal malignancies and premalignancies, and genital warts in both sexes ages 9-45.
It may be years, however, before the impact of the newer polyvalent formulation is felt. “While the first vaccine has been successful against the prevalent strains of HPV linked to cervical cancer, it’s a little early to call it for the newer vaccine since oropharyngeal cancers tend to develop later in older men,” Cuccaro said. “But the types of HPV linked to mouth and throat cancers and covered by the newer vaccines are much less prevalent in those who are vaccinated. The strains not covered in the vaccine you see are equally present in the vaccinated and non-vaccinated.”
Angela L. Myers, MD, MPH, division director of infectious diseases and medical director of the Center for Wellbeing at Children’s Mercy in Kansas City, Missouri, added, “Unlike for cervical cancer, there are no screening programs for oropharyngeal lesions, so you have to wait to see rates until actual cancer develops.”
A 2023 review reported that HPV vaccination reduced levels of oropharyngeal HPV positivity in men, strengthening the case for pangender immunization.
And in a recent phase 3 doubled-blind trial, GARDASIL 9 reduced the incidence of anogenital persistent infection caused by nine types of HPV compared with a placebo.
Increasing Uptake
The current public health aim is to have 80% of young people in the targeted age group vaccinated with two doses. Today, uptake among those 9-26 years old stands at about 78% of girls and 75% of boys for the first dose, said Annunziata. “But it’s only about 61% for the two doses in the current series, and we want to improve that.”
Some parents may still harbor fears that immunizing teens and tweens — both the American Academy of Pediatrics and the American Cancer Society recommend immunization at age 9 — will open the door to precocious sexual activity.
“But overall, uptake in tweens and young teens has increased because the messaging has changed,” said Myers, with the rationale now focusing on cancer prevention not sexual-infection prophylaxis. “This is similar to the hepatitis B vaccine, which used to be given to young adults and is now given to newborns to prevent cancer.”
Cuccaro added that a proactive presentation by healthcare professionals has a significant effect on vaccine uptake and increases the odds of vaccination ninefold. “Providers should take a presumptive approach and avoid just offering the vaccine as an option. It should be included with regular childhood vaccinations,” she said. “And the advantage of starting early at age 9 is that you can spread the doses out across other regular childhood vaccinations, whereas if you start at age 11, you need to add the HPV vaccine to three other vaccines that are given at that time.”
After age 15, three doses are necessary. “Providers should stress to parents that it’s most effective when given before young people become sexually active and exposed to HPV,” Cuccaro said. And Myers stressed that despite the vaccine’s effectiveness, routine screening for cervical premalignancies is still important.
Despite increasing coverage, vaccination rates have some distance to go before the public health target of at least 80% uptake of the series in the targeted age group, Cuccaro cautioned.
On the global stage, barriers to immunization remain, but the World Health Organization has endorsed a campaign to eradicate cervical cancer through HPV vaccination. It has predicted that the 21st century may be the last to experience HPV-associated cancers, currently responsible for more than 300,000 annual deaths worldwide.
A Brief History of HPV Vaccines
- 1951. Cervical cancer patient Henrietta Lacks’ rapidly dividing cervical cells are collected by George Otto Gey at Johns Hopkins Hospital. They create the first immortal cell line (HeLa) used to study cancers and vaccines worldwide.
- 1976. Harald zur Hausen suggests that genital wart-associated HPV, not herpes simplex, is the probable cause of cervical cancer.
- 1983. HPV is confirmed as a cause of cancer.
- 1991. The first HPV vaccine is developed.
- 2002. Proof of principle and protective efficacy for the monovalent HPV 16 are shown.
- 2006. Merck’s Gardasil 4 (HPV 4) is FDA approved in girls ages 9-26 for protection against strains 6, 11, 16, and 18 — the cause of more than 70% of cervical cancer cases.
- 2009. Approval of Gardasil 4 is expanded to boys ages 9-26 for the prevention of genital warts.
- 2009. The FDA approves GlaxoSmithKline’s Cervarix (HPV 16 and 18) for girls and young women. The vaccine was withdrawn from the US market in 2016 following the success of Gardasil 9 but is used abroad for HPV cancer prevention.
- 2014. The 9-valent recombinant vaccine Gardasil 9 is FDA approved for protection against several low-risk, wart-causing HPV strains as well as the high-risk cancer strains targeted by HPV 4.
- 2018. The FDA expands approval to include females and males 27-45 years old.
- 2020. The FDA extends approval of Gardasil 9 to include prevention not only of cervical cancer but also, vaginal, vulvar, anal, oropharyngeal, and other head and neck cancers.
Annunziata, Cuccaro, and Myers had no competing interests to declare.
A version of this article appeared on Medscape.com.
Molecular Stool Testing Could Cut Post-Polypectomy Colonoscopies by 15%-41%
It might also reduce colonoscopies by an estimated 15%-41%.
The greatest reduction would likely be achieved by annual FIT-based surveillance, especially with FIT FOB-Gold at a threshold of at least 32 µg/g feces, according to findings from the Dutch MOCCAS study published in Gastroenterology.
In this cross-sectional observational study, the multitarget DNA test outperformed FIT for detecting advanced precursor lesions, especially serrated polyps. According to long-term-impact mathematical modeling, however, DNA-based surveillance would be more costly than colonoscopy surveillance, whereas FIT would save costs.
“With the worldwide implementation of FIT-based screening programs, following a positive test, many more people enter surveillance programs after polypectomy. This results in an increased pressure on the colonoscopy capacity and healthcare budgets,” lead author Beatriz Carvalho, PhD, a molecular biologist in the Department of Pathology of the Netherlands Cancer Institute in Amsterdam, said in an interview.
A noninvasive strategy could ease the surveillance burden on healthcare resources and be more palatable to patients. Post-polypectomy guidelines have already been relaxed to allow less intensive surveillance.
“Our working hypothesis was that although the sensitivity of a singular molecular test to detect CRC or advanced adenomas is lower than that of colonoscopy, repeating molecular stool testing would yield similar detection rates as colonoscopy-based surveillance. And our hypothesis was confirmed,” Carvalho said.
The results of the MOCCAS study align with those of other studies that found that FIT could be safely applied as a triage test in post-polypectomy surveillance and could safely extend the interval of surveillance colonoscopy. “But these studies did not include a long-term impact analysis,” she said. “The next step is to run a prospective interventional study to validate the MOCCAS findings.”
Offering an outsider’s perspective on the findings, Uri Ladabaum, MD, director of the Gastrointestinal Cancer Prevention Program and a professor of medicine at Stanford University School of Medicine in Palo Alto, California, said the real-world results on lesion detection and the multi-year-horizon modeling performed are provocative and point to the potential to base post-polypectomy surveillance on stool tests.
He cautioned, however, that the proposed paradigm requires the ability to deploy FIT-based surveillance with broad flexibility in relation to hemoglobin-detection thresholds and testing interval, depending on the specific FIT that is chosen, with the possibility these may differ by setting based on the characteristics of the population and the relevant epidemiology.
“Such flexibility may or may not be technically feasible in all settings — for instance, in the current US regulatory context, it would be challenging to implement FIT-based testing at newly adjusted detection thresholds,” he said.
Nevertheless, the study provides a strong rationale for a real-world study of FIT-based surveillance, he added. “The choice of specific FIT and detection threshold will be critical. Multiple rounds of FIT-based surveillance, that is, years of prospective surveillance, will be needed to constitute a properly designed comparison with surveillance colonoscopy.”
Study Details
The cross-sectional observational study included individuals aged 50-75 years who provided stool samples for the DNA test and two FITs. Test accuracy was calculated for all surveillance indications.
For the post-polypectomy indication only, which is the most common and associated with a relatively low CRC risk, the long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer model. Stool-based strategies were simulated to tune each test’s positivity threshold to obtain strategies that are at least as effective as colonoscopy surveillance.
A total of 3453 individuals had results for all stool tests and colonoscopy; among them, 2226 had previously undergone polypectomy, 1003 had a history of CRC, and 224 had a familial risk.
Areas under the receiver operating characteristic curve for advanced neoplasia were as follows:
- 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test
- 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR
- 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold
Stool-based surveillance was estimated to be at least as effective as colonoscopy surveillance and required 5.6 to 9.5 stool tests over a person’s lifetime. DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs.
“These findings provide a basis to embark on a prospective intervention study to assess the clinical utility of FIT as an alternative to colonoscopy surveillance in a post-polypectomy CRC surveillance population,” the authors wrote.
In the United States, Ladabaum said, it would likely be possible to find FIT-based strategies that closely approximate or match surveillance colonoscopy — “if we could deploy FIT with the required flexibility, for example, by adjusting the threshold and if the reference surveillance standard were somewhat relaxed compared with current guidelines.”
He worries, however, that if FIT for screening and FIT for surveillance were optimized at different hemoglobin detection thresholds, “there could be confusion and room for error in real-world clinical implementation.”
The authors called for research to increase understanding of the mechanisms underlying progression from adenomas to malignancy over time, which may yield better biomarkers to improve stool test accuracy.
This study was funded by the Alpe d’HuZes charity and the Dutch Cancer Society. Exact Sciences provided test equipment and performed multitarget stool DNA test analysis. Sentinel Diagnostics provided equipment and reagents.
Carvalho and Veerle M. H. Coupé, PhD, disclosed several patents pending and/or issued. Other coauthors disclosed multiple financial relationships with private companies, including Exact Sciences and Sentinel, for research support, travel, board membership, advisory or speaker fees, consulting, employment, stock ownership, or patents.
Ladabaum disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
It might also reduce colonoscopies by an estimated 15%-41%.
The greatest reduction would likely be achieved by annual FIT-based surveillance, especially with FIT FOB-Gold at a threshold of at least 32 µg/g feces, according to findings from the Dutch MOCCAS study published in Gastroenterology.
In this cross-sectional observational study, the multitarget DNA test outperformed FIT for detecting advanced precursor lesions, especially serrated polyps. According to long-term-impact mathematical modeling, however, DNA-based surveillance would be more costly than colonoscopy surveillance, whereas FIT would save costs.
“With the worldwide implementation of FIT-based screening programs, following a positive test, many more people enter surveillance programs after polypectomy. This results in an increased pressure on the colonoscopy capacity and healthcare budgets,” lead author Beatriz Carvalho, PhD, a molecular biologist in the Department of Pathology of the Netherlands Cancer Institute in Amsterdam, said in an interview.
A noninvasive strategy could ease the surveillance burden on healthcare resources and be more palatable to patients. Post-polypectomy guidelines have already been relaxed to allow less intensive surveillance.
“Our working hypothesis was that although the sensitivity of a singular molecular test to detect CRC or advanced adenomas is lower than that of colonoscopy, repeating molecular stool testing would yield similar detection rates as colonoscopy-based surveillance. And our hypothesis was confirmed,” Carvalho said.
The results of the MOCCAS study align with those of other studies that found that FIT could be safely applied as a triage test in post-polypectomy surveillance and could safely extend the interval of surveillance colonoscopy. “But these studies did not include a long-term impact analysis,” she said. “The next step is to run a prospective interventional study to validate the MOCCAS findings.”
Offering an outsider’s perspective on the findings, Uri Ladabaum, MD, director of the Gastrointestinal Cancer Prevention Program and a professor of medicine at Stanford University School of Medicine in Palo Alto, California, said the real-world results on lesion detection and the multi-year-horizon modeling performed are provocative and point to the potential to base post-polypectomy surveillance on stool tests.
He cautioned, however, that the proposed paradigm requires the ability to deploy FIT-based surveillance with broad flexibility in relation to hemoglobin-detection thresholds and testing interval, depending on the specific FIT that is chosen, with the possibility these may differ by setting based on the characteristics of the population and the relevant epidemiology.
“Such flexibility may or may not be technically feasible in all settings — for instance, in the current US regulatory context, it would be challenging to implement FIT-based testing at newly adjusted detection thresholds,” he said.
Nevertheless, the study provides a strong rationale for a real-world study of FIT-based surveillance, he added. “The choice of specific FIT and detection threshold will be critical. Multiple rounds of FIT-based surveillance, that is, years of prospective surveillance, will be needed to constitute a properly designed comparison with surveillance colonoscopy.”
Study Details
The cross-sectional observational study included individuals aged 50-75 years who provided stool samples for the DNA test and two FITs. Test accuracy was calculated for all surveillance indications.
For the post-polypectomy indication only, which is the most common and associated with a relatively low CRC risk, the long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer model. Stool-based strategies were simulated to tune each test’s positivity threshold to obtain strategies that are at least as effective as colonoscopy surveillance.
A total of 3453 individuals had results for all stool tests and colonoscopy; among them, 2226 had previously undergone polypectomy, 1003 had a history of CRC, and 224 had a familial risk.
Areas under the receiver operating characteristic curve for advanced neoplasia were as follows:
- 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test
- 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR
- 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold
Stool-based surveillance was estimated to be at least as effective as colonoscopy surveillance and required 5.6 to 9.5 stool tests over a person’s lifetime. DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs.
“These findings provide a basis to embark on a prospective intervention study to assess the clinical utility of FIT as an alternative to colonoscopy surveillance in a post-polypectomy CRC surveillance population,” the authors wrote.
In the United States, Ladabaum said, it would likely be possible to find FIT-based strategies that closely approximate or match surveillance colonoscopy — “if we could deploy FIT with the required flexibility, for example, by adjusting the threshold and if the reference surveillance standard were somewhat relaxed compared with current guidelines.”
He worries, however, that if FIT for screening and FIT for surveillance were optimized at different hemoglobin detection thresholds, “there could be confusion and room for error in real-world clinical implementation.”
The authors called for research to increase understanding of the mechanisms underlying progression from adenomas to malignancy over time, which may yield better biomarkers to improve stool test accuracy.
This study was funded by the Alpe d’HuZes charity and the Dutch Cancer Society. Exact Sciences provided test equipment and performed multitarget stool DNA test analysis. Sentinel Diagnostics provided equipment and reagents.
Carvalho and Veerle M. H. Coupé, PhD, disclosed several patents pending and/or issued. Other coauthors disclosed multiple financial relationships with private companies, including Exact Sciences and Sentinel, for research support, travel, board membership, advisory or speaker fees, consulting, employment, stock ownership, or patents.
Ladabaum disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
It might also reduce colonoscopies by an estimated 15%-41%.
The greatest reduction would likely be achieved by annual FIT-based surveillance, especially with FIT FOB-Gold at a threshold of at least 32 µg/g feces, according to findings from the Dutch MOCCAS study published in Gastroenterology.
In this cross-sectional observational study, the multitarget DNA test outperformed FIT for detecting advanced precursor lesions, especially serrated polyps. According to long-term-impact mathematical modeling, however, DNA-based surveillance would be more costly than colonoscopy surveillance, whereas FIT would save costs.
“With the worldwide implementation of FIT-based screening programs, following a positive test, many more people enter surveillance programs after polypectomy. This results in an increased pressure on the colonoscopy capacity and healthcare budgets,” lead author Beatriz Carvalho, PhD, a molecular biologist in the Department of Pathology of the Netherlands Cancer Institute in Amsterdam, said in an interview.
A noninvasive strategy could ease the surveillance burden on healthcare resources and be more palatable to patients. Post-polypectomy guidelines have already been relaxed to allow less intensive surveillance.
“Our working hypothesis was that although the sensitivity of a singular molecular test to detect CRC or advanced adenomas is lower than that of colonoscopy, repeating molecular stool testing would yield similar detection rates as colonoscopy-based surveillance. And our hypothesis was confirmed,” Carvalho said.
The results of the MOCCAS study align with those of other studies that found that FIT could be safely applied as a triage test in post-polypectomy surveillance and could safely extend the interval of surveillance colonoscopy. “But these studies did not include a long-term impact analysis,” she said. “The next step is to run a prospective interventional study to validate the MOCCAS findings.”
Offering an outsider’s perspective on the findings, Uri Ladabaum, MD, director of the Gastrointestinal Cancer Prevention Program and a professor of medicine at Stanford University School of Medicine in Palo Alto, California, said the real-world results on lesion detection and the multi-year-horizon modeling performed are provocative and point to the potential to base post-polypectomy surveillance on stool tests.
He cautioned, however, that the proposed paradigm requires the ability to deploy FIT-based surveillance with broad flexibility in relation to hemoglobin-detection thresholds and testing interval, depending on the specific FIT that is chosen, with the possibility these may differ by setting based on the characteristics of the population and the relevant epidemiology.
“Such flexibility may or may not be technically feasible in all settings — for instance, in the current US regulatory context, it would be challenging to implement FIT-based testing at newly adjusted detection thresholds,” he said.
Nevertheless, the study provides a strong rationale for a real-world study of FIT-based surveillance, he added. “The choice of specific FIT and detection threshold will be critical. Multiple rounds of FIT-based surveillance, that is, years of prospective surveillance, will be needed to constitute a properly designed comparison with surveillance colonoscopy.”
Study Details
The cross-sectional observational study included individuals aged 50-75 years who provided stool samples for the DNA test and two FITs. Test accuracy was calculated for all surveillance indications.
For the post-polypectomy indication only, which is the most common and associated with a relatively low CRC risk, the long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer model. Stool-based strategies were simulated to tune each test’s positivity threshold to obtain strategies that are at least as effective as colonoscopy surveillance.
A total of 3453 individuals had results for all stool tests and colonoscopy; among them, 2226 had previously undergone polypectomy, 1003 had a history of CRC, and 224 had a familial risk.
Areas under the receiver operating characteristic curve for advanced neoplasia were as follows:
- 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test
- 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR
- 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold
Stool-based surveillance was estimated to be at least as effective as colonoscopy surveillance and required 5.6 to 9.5 stool tests over a person’s lifetime. DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs.
“These findings provide a basis to embark on a prospective intervention study to assess the clinical utility of FIT as an alternative to colonoscopy surveillance in a post-polypectomy CRC surveillance population,” the authors wrote.
In the United States, Ladabaum said, it would likely be possible to find FIT-based strategies that closely approximate or match surveillance colonoscopy — “if we could deploy FIT with the required flexibility, for example, by adjusting the threshold and if the reference surveillance standard were somewhat relaxed compared with current guidelines.”
He worries, however, that if FIT for screening and FIT for surveillance were optimized at different hemoglobin detection thresholds, “there could be confusion and room for error in real-world clinical implementation.”
The authors called for research to increase understanding of the mechanisms underlying progression from adenomas to malignancy over time, which may yield better biomarkers to improve stool test accuracy.
This study was funded by the Alpe d’HuZes charity and the Dutch Cancer Society. Exact Sciences provided test equipment and performed multitarget stool DNA test analysis. Sentinel Diagnostics provided equipment and reagents.
Carvalho and Veerle M. H. Coupé, PhD, disclosed several patents pending and/or issued. Other coauthors disclosed multiple financial relationships with private companies, including Exact Sciences and Sentinel, for research support, travel, board membership, advisory or speaker fees, consulting, employment, stock ownership, or patents.
Ladabaum disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
The Heavy Physical and Psychological Burden of Premenstrual Dysphoric Disorder
Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.
Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.
The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.
“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”
Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.
Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
Etiology
Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.
Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
Risk Factors
These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.
A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.
Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
Diagnosis
Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.
Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.
Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.
“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”
PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.
In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
Treatments
In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.
Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.
Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.
“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.
Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.
If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.
Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.
Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.
Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.
Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.
Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.
Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.
Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.
A small study suggested that supplemental zinc may improve both physical and psychological symptoms.
Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.
Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.
The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”
Ireland and Haque had no competing interests with regard to their comments.
A version of this article first appeared on Medscape.com.
Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.
Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.
The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.
“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”
Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.
Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
Etiology
Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.
Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
Risk Factors
These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.
A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.
Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
Diagnosis
Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.
Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.
Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.
“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”
PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.
In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
Treatments
In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.
Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.
Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.
“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.
Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.
If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.
Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.
Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.
Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.
Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.
Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.
Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.
Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.
A small study suggested that supplemental zinc may improve both physical and psychological symptoms.
Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.
Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.
The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”
Ireland and Haque had no competing interests with regard to their comments.
A version of this article first appeared on Medscape.com.
Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.
Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.
The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.
“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”
Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.
Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
Etiology
Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.
Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
Risk Factors
These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.
A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.
Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
Diagnosis
Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.
Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.
Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.
“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”
PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.
In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
Treatments
In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.
Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.
Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.
“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.
Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.
If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.
Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.
Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.
Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.
Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.
Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.
Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.
Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.
A small study suggested that supplemental zinc may improve both physical and psychological symptoms.
Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.
Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.
The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”
Ireland and Haque had no competing interests with regard to their comments.
A version of this article first appeared on Medscape.com.
GLP-1 Receptor Agonists Reduce Suicidal Behavior in Adolescents With Obesity
, a large international retrospective study found.
A study published in JAMA Pediatrics suggested that GLP-1 RAs such as semaglutide, liraglutide, and tirzepatide, which are widely used to treat type 2 diabetes (T2D), have a favorable psychiatric safety profile and open up potential avenues for prospective studies of psychiatric outcomes in adolescents with obesity.
Investigators Liya Kerem, MD, MSc, and Joshua Stokar, MD, of Hadassah University Medical Center in Jerusalem, Israel, reported that the reduced risk in GLP-1 RA recipients was maintained up to 3 years follow-up compared with propensity score–matched controls treated with behavioral interventions alone.
“These findings support the notion that childhood obesity does not result from lack of willpower and shed light on underlying mechanisms that can be targeted by pharmacotherapy.” Kerem and Stokar wrote.
Other research has suggested these agents have neurobiologic effects unrelated to weight loss that positively affect mood and mental health.
Study Details
The analysis included data from December 2019 to June 2024, drawn from 120 international healthcare organizations, mainly in the United States. A total of 4052 racially and ethnically diverse adolescents with obesity (aged 12-18 years [mean age, about 15.5 years]) being treated with an anti-obesity intervention were identified for the GLP-1 RA cohort and 50,112 for the control cohort. The arms were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and healthcare access.
Propensity score matching (PSM) resulted in 3456 participants in each of two balanced cohorts.
Before PSM, intervention patients were older (mean age, 15.5 vs 14.7 years), were more likely to be female (59% vs 49%), and had a higher body mass index (41.9 vs 33.8). They also had a higher prevalence of diabetes (40% vs 4%) and treatment with antidiabetic medications.
GLP-1 RA recipients also had a history of psychiatric diagnoses (17% vs 9% for mood disorders) and psychiatric medications (18% vs 7% for antidepressants). Previous use of non–GLP-1 RA anti-obesity medications was uncommon in the cohort overall, although more common in the GLP-1 RA cohort (2.5% vs 0.2% for phentermine).
Prescription of GLP-1 RA was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up: 1.45% vs 2.26% (hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). It was also associated with a higher rate of gastrointestinal symptoms: 6.9% vs 5.4% (HR, 1.41; 95% CI, 1.12-1.78; P = .003). There was no difference in rates of upper respiratory tract infections (URTIs), although some research suggests these agents reduce URTIs.
Mechanisms
The etiology of childhood obesity is complex and multifactorial, the authors wrote, and genetic predisposition to adiposity, an obesogenic environment, and a sedentary lifestyle synergistically contribute to its development. Variants in genes active in the hypothalamic appetite-regulation neurocircuitry appear to be associated with the development of childhood and adolescent obesity.
The authors noted that adolescence carries an increased risk for psychiatric disorders and suicidal ideation. “The amelioration of obesity could indirectly improve these psychiatric comorbidities,” they wrote. In addition, preclinical studies suggested that GLP-1 RA may improve depression-related neuropathology, including neuroinflammation and neurotransmitter imbalance, and may promote neurogenesis.
A recent meta-analysis found that adults with T2D treated with GLP-1 RA showed significant reduction in depression scale scores compared with those treated with non-GLP-1 RA antidiabetic medications.
Commenting on the study but not involved in it, psychiatrist Robert H. Dicker, MD, associate director of child and adolescent psychiatry at Northwell Zucker Hillside Hospital in Glen Oaks, New York, cautioned that these are preliminary data limited by a retrospective review, not a prospective double-blind, placebo-controlled study.
“The mechanism is unknown — is it a direct effect on weight loss with an improvement of quality of life, more positive feedback by the community, enhanced ability to exercise, and a decrease in depressive symptoms?” he asked.
Dicker suggested an alternative hypothesis: Does the GLP-1 RA have a direct effect on neurotransmitters and inflammation and, thus, an impact on mood, emotional regulation, impulse control, and suicide?
“To further answer these questions, prospective studies must be conducted. It is far too early to conclude that these medications are effective in treating mood disorders in our youth,” Dicker said. “But it is promising that these treatments do not appear to increase suicidal ideas and behavior.”
Adding another outsider’s perspective on the study, Suzanne E. Cuda, MD, FOMA, FAAP, a pediatrician who treats childhood obesity in San Antonio, said that while there was no risk for increased psychiatric disease and a suggestion that GLP-1 RAs may reduce suicidal ideation or attempts, “I don’t think this translates to a treatment for depression in adolescents. Nor does this study indicate there could be a decrease in depression due specifically to the use of GLP1Rs. If the results in this study are replicated, however, it would be reassuring to know that adolescents would not be at risk for an increase in suicidal ideation or attempts.”
This study had no external funding. Kerem reported receiving personal fees from Novo Nordisk for lectures on childhood obesity outside of the submitted work. No other disclosures were reported. Dicker and Cuda had no competing interests relevant to their comments.
A version of this article appeared on Medscape.com.
, a large international retrospective study found.
A study published in JAMA Pediatrics suggested that GLP-1 RAs such as semaglutide, liraglutide, and tirzepatide, which are widely used to treat type 2 diabetes (T2D), have a favorable psychiatric safety profile and open up potential avenues for prospective studies of psychiatric outcomes in adolescents with obesity.
Investigators Liya Kerem, MD, MSc, and Joshua Stokar, MD, of Hadassah University Medical Center in Jerusalem, Israel, reported that the reduced risk in GLP-1 RA recipients was maintained up to 3 years follow-up compared with propensity score–matched controls treated with behavioral interventions alone.
“These findings support the notion that childhood obesity does not result from lack of willpower and shed light on underlying mechanisms that can be targeted by pharmacotherapy.” Kerem and Stokar wrote.
Other research has suggested these agents have neurobiologic effects unrelated to weight loss that positively affect mood and mental health.
Study Details
The analysis included data from December 2019 to June 2024, drawn from 120 international healthcare organizations, mainly in the United States. A total of 4052 racially and ethnically diverse adolescents with obesity (aged 12-18 years [mean age, about 15.5 years]) being treated with an anti-obesity intervention were identified for the GLP-1 RA cohort and 50,112 for the control cohort. The arms were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and healthcare access.
Propensity score matching (PSM) resulted in 3456 participants in each of two balanced cohorts.
Before PSM, intervention patients were older (mean age, 15.5 vs 14.7 years), were more likely to be female (59% vs 49%), and had a higher body mass index (41.9 vs 33.8). They also had a higher prevalence of diabetes (40% vs 4%) and treatment with antidiabetic medications.
GLP-1 RA recipients also had a history of psychiatric diagnoses (17% vs 9% for mood disorders) and psychiatric medications (18% vs 7% for antidepressants). Previous use of non–GLP-1 RA anti-obesity medications was uncommon in the cohort overall, although more common in the GLP-1 RA cohort (2.5% vs 0.2% for phentermine).
Prescription of GLP-1 RA was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up: 1.45% vs 2.26% (hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). It was also associated with a higher rate of gastrointestinal symptoms: 6.9% vs 5.4% (HR, 1.41; 95% CI, 1.12-1.78; P = .003). There was no difference in rates of upper respiratory tract infections (URTIs), although some research suggests these agents reduce URTIs.
Mechanisms
The etiology of childhood obesity is complex and multifactorial, the authors wrote, and genetic predisposition to adiposity, an obesogenic environment, and a sedentary lifestyle synergistically contribute to its development. Variants in genes active in the hypothalamic appetite-regulation neurocircuitry appear to be associated with the development of childhood and adolescent obesity.
The authors noted that adolescence carries an increased risk for psychiatric disorders and suicidal ideation. “The amelioration of obesity could indirectly improve these psychiatric comorbidities,” they wrote. In addition, preclinical studies suggested that GLP-1 RA may improve depression-related neuropathology, including neuroinflammation and neurotransmitter imbalance, and may promote neurogenesis.
A recent meta-analysis found that adults with T2D treated with GLP-1 RA showed significant reduction in depression scale scores compared with those treated with non-GLP-1 RA antidiabetic medications.
Commenting on the study but not involved in it, psychiatrist Robert H. Dicker, MD, associate director of child and adolescent psychiatry at Northwell Zucker Hillside Hospital in Glen Oaks, New York, cautioned that these are preliminary data limited by a retrospective review, not a prospective double-blind, placebo-controlled study.
“The mechanism is unknown — is it a direct effect on weight loss with an improvement of quality of life, more positive feedback by the community, enhanced ability to exercise, and a decrease in depressive symptoms?” he asked.
Dicker suggested an alternative hypothesis: Does the GLP-1 RA have a direct effect on neurotransmitters and inflammation and, thus, an impact on mood, emotional regulation, impulse control, and suicide?
“To further answer these questions, prospective studies must be conducted. It is far too early to conclude that these medications are effective in treating mood disorders in our youth,” Dicker said. “But it is promising that these treatments do not appear to increase suicidal ideas and behavior.”
Adding another outsider’s perspective on the study, Suzanne E. Cuda, MD, FOMA, FAAP, a pediatrician who treats childhood obesity in San Antonio, said that while there was no risk for increased psychiatric disease and a suggestion that GLP-1 RAs may reduce suicidal ideation or attempts, “I don’t think this translates to a treatment for depression in adolescents. Nor does this study indicate there could be a decrease in depression due specifically to the use of GLP1Rs. If the results in this study are replicated, however, it would be reassuring to know that adolescents would not be at risk for an increase in suicidal ideation or attempts.”
This study had no external funding. Kerem reported receiving personal fees from Novo Nordisk for lectures on childhood obesity outside of the submitted work. No other disclosures were reported. Dicker and Cuda had no competing interests relevant to their comments.
A version of this article appeared on Medscape.com.
, a large international retrospective study found.
A study published in JAMA Pediatrics suggested that GLP-1 RAs such as semaglutide, liraglutide, and tirzepatide, which are widely used to treat type 2 diabetes (T2D), have a favorable psychiatric safety profile and open up potential avenues for prospective studies of psychiatric outcomes in adolescents with obesity.
Investigators Liya Kerem, MD, MSc, and Joshua Stokar, MD, of Hadassah University Medical Center in Jerusalem, Israel, reported that the reduced risk in GLP-1 RA recipients was maintained up to 3 years follow-up compared with propensity score–matched controls treated with behavioral interventions alone.
“These findings support the notion that childhood obesity does not result from lack of willpower and shed light on underlying mechanisms that can be targeted by pharmacotherapy.” Kerem and Stokar wrote.
Other research has suggested these agents have neurobiologic effects unrelated to weight loss that positively affect mood and mental health.
Study Details
The analysis included data from December 2019 to June 2024, drawn from 120 international healthcare organizations, mainly in the United States. A total of 4052 racially and ethnically diverse adolescents with obesity (aged 12-18 years [mean age, about 15.5 years]) being treated with an anti-obesity intervention were identified for the GLP-1 RA cohort and 50,112 for the control cohort. The arms were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and healthcare access.
Propensity score matching (PSM) resulted in 3456 participants in each of two balanced cohorts.
Before PSM, intervention patients were older (mean age, 15.5 vs 14.7 years), were more likely to be female (59% vs 49%), and had a higher body mass index (41.9 vs 33.8). They also had a higher prevalence of diabetes (40% vs 4%) and treatment with antidiabetic medications.
GLP-1 RA recipients also had a history of psychiatric diagnoses (17% vs 9% for mood disorders) and psychiatric medications (18% vs 7% for antidepressants). Previous use of non–GLP-1 RA anti-obesity medications was uncommon in the cohort overall, although more common in the GLP-1 RA cohort (2.5% vs 0.2% for phentermine).
Prescription of GLP-1 RA was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up: 1.45% vs 2.26% (hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). It was also associated with a higher rate of gastrointestinal symptoms: 6.9% vs 5.4% (HR, 1.41; 95% CI, 1.12-1.78; P = .003). There was no difference in rates of upper respiratory tract infections (URTIs), although some research suggests these agents reduce URTIs.
Mechanisms
The etiology of childhood obesity is complex and multifactorial, the authors wrote, and genetic predisposition to adiposity, an obesogenic environment, and a sedentary lifestyle synergistically contribute to its development. Variants in genes active in the hypothalamic appetite-regulation neurocircuitry appear to be associated with the development of childhood and adolescent obesity.
The authors noted that adolescence carries an increased risk for psychiatric disorders and suicidal ideation. “The amelioration of obesity could indirectly improve these psychiatric comorbidities,” they wrote. In addition, preclinical studies suggested that GLP-1 RA may improve depression-related neuropathology, including neuroinflammation and neurotransmitter imbalance, and may promote neurogenesis.
A recent meta-analysis found that adults with T2D treated with GLP-1 RA showed significant reduction in depression scale scores compared with those treated with non-GLP-1 RA antidiabetic medications.
Commenting on the study but not involved in it, psychiatrist Robert H. Dicker, MD, associate director of child and adolescent psychiatry at Northwell Zucker Hillside Hospital in Glen Oaks, New York, cautioned that these are preliminary data limited by a retrospective review, not a prospective double-blind, placebo-controlled study.
“The mechanism is unknown — is it a direct effect on weight loss with an improvement of quality of life, more positive feedback by the community, enhanced ability to exercise, and a decrease in depressive symptoms?” he asked.
Dicker suggested an alternative hypothesis: Does the GLP-1 RA have a direct effect on neurotransmitters and inflammation and, thus, an impact on mood, emotional regulation, impulse control, and suicide?
“To further answer these questions, prospective studies must be conducted. It is far too early to conclude that these medications are effective in treating mood disorders in our youth,” Dicker said. “But it is promising that these treatments do not appear to increase suicidal ideas and behavior.”
Adding another outsider’s perspective on the study, Suzanne E. Cuda, MD, FOMA, FAAP, a pediatrician who treats childhood obesity in San Antonio, said that while there was no risk for increased psychiatric disease and a suggestion that GLP-1 RAs may reduce suicidal ideation or attempts, “I don’t think this translates to a treatment for depression in adolescents. Nor does this study indicate there could be a decrease in depression due specifically to the use of GLP1Rs. If the results in this study are replicated, however, it would be reassuring to know that adolescents would not be at risk for an increase in suicidal ideation or attempts.”
This study had no external funding. Kerem reported receiving personal fees from Novo Nordisk for lectures on childhood obesity outside of the submitted work. No other disclosures were reported. Dicker and Cuda had no competing interests relevant to their comments.
A version of this article appeared on Medscape.com.
From JAMA Pediatrics
Live Rotavirus Vaccine Safe for Newborns of Biologic-Treated Moms With IBD
No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.
The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.
“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.
“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.
They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.
Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.
“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.
“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.
The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.
“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”
She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”
Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
The Study
The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.
For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.
The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.
As anticipated, infant immune function was normal regardless of circulating drug levels.
The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.
This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.
A version of this article first appeared on Medscape.com.
No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.
The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.
“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.
“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.
They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.
Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.
“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.
“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.
The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.
“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”
She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”
Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
The Study
The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.
For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.
The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.
As anticipated, infant immune function was normal regardless of circulating drug levels.
The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.
This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.
A version of this article first appeared on Medscape.com.
No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.
The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.
“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.
“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.
They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.
Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.
“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.
“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.
The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.
“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”
She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”
Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
The Study
The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.
For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.
The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.
As anticipated, infant immune function was normal regardless of circulating drug levels.
The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.
This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
New Biologic Tulisokibart Beats Placebo in Ulcerative Colitis Trial
In one cohort of 135 patients, the primary endpoint of clinical remission occurred in 26% of those given the novel antibody to tumor necrosis factor–like cytokine 1A (TL1A) vs 1% given placebo (95% CI, 14-37, P < .001). In a smaller cohort of 43 patients genetically pretested for likely response to the new biologic, remission after treatment was only slightly higher at 32% vs 11% (95% CI, 2-38, P = .02).
The incidence of adverse events was similar in both arms, and most events were mild.
The 12-week induction trial, conducted in 14 countries by the ARTEMIS-UC Study Group and led by Bruce E. Sands, MD, MS, AGAF, a professor of medicine at Icahn School of Medicine at Mount Sinai and system chief in the Division of Gastroenterology at Mount Sinai Health System in New York City, was published in The New England Journal of Medicine.
“Our results suggest that important clinical benefit may be achieved through TL1A blockade in patients with UC,” Dr. Sands said in an interview, adding that this is the first rigorous study of a drug class with an entirely new mechanism of action that may be beneficial in other immune-mediated and fibrotic diseases.
“And it is also the first prospective randomized controlled trial in IBD to incorporate a precision-medicine approach using a predictive biomarker for response in a drug development program,” he added.
Dr. Sands stressed the urgent need for new therapies since, despite the approval of multiple new classes of agents, both small molecules and biologics, “there is still a plateau of efficacy in that less than 50% of patients achieve remission at a year.”
He added that UC may progress over time owing to fibrosis of the bowel, a condition not directly or safely addressed by any existing therapies. “Identifying novel targets such as TL1A may allow us to address a different subpopulation of patients who may not respond to the targets addressed by existing therapies,” he said.
In agreement is Jason K. Hou, MD, MS, AGAF, an associate professor of medicine at Baylor College of Medicine and section chief of gastroenterology at Michael E. DeBakey VA Medical Center, both in Houston, Texas. “Although it’s a very exciting time with more options in the last few years for treating UC, even inhibitors with new agents such as JAK inhibitors and interleukin 23 antagonists, many patients have no or only a partial response,” he said in an interview. “Targeting molecules, which has been studied for decades, may offer more than a shot in the dark.”
Why Target TL1A?
Genome-wide studies have shown elevated TL1A, a member of the tumor necrosis factor superfamily, in patients with inflammatory bowel disease (IBD).
“The interaction of TL1A and its ligand, death domain receptor 3, contributes to the immune-mediated inflammation and fibrosis seen in IBD through the downstream production of proinflammatory cytokines by multiple different immune cells, and the elaboration of collagen by fibroblasts,” Dr. Sands explained.
With the intention of targeting TL1A, his group randomly assigned patients with moderate to severe active UC who were glucocorticoid dependent or had not responded to conventional or advanced therapies, with disease extending a minimum of 15 cm from the anal verge. Across arms, the age of the mainly White, non-Hispanic participants ranged from about 37 to about 42, 35%-53% were female, and disease duration was approximately 6-8 years.
The arms received either placebo or intravenous tulisokibart at 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10. Cohort 1 included patients regardless of biomarker status for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response.
Dr. Hou was surprised that response to tulisokibart vs placebo was not greater in test-identified probable responders. “The biomarker didn’t make a huge difference, just a numerical one,” he said. “It may be that more genes are involved than the test could identify, and response is more complicated. Or perhaps the placebo response was particularly high in this small group. We need a deeper dive into why.”
Earlier Application?
“This was a phase 2 study, so it’s too soon to say if tulisokibart could be used as early therapy or in severe disease,” Sands said. “However, the excellent safety profile and efficacy suggest that these populations should be explored in later studies.
Further work is needed to validate the test to predict higher likelihood of response, he added, and recruiting for a phase 3 study is now underway.
The study was supported by Prometheus Biosciences, a subsidiary of Merck. Dr. Sands disclosed multiple ties to private companies, including research support, consulting, data safety monitoring, travel, a gift, and a stock option. Several coauthors reported, variously, research support from and/or consulting for multiple private companies. Others reported employment, variously, with Prometheus and/or Merck, Spyre Therapeutics, and Mirador Therapeutics, or patent holding for IBD drugs. Dr. Hou had no relevant competing interests to disclose but will participate in the phase 3 trial.
A version of this article appeared on Medscape.com.
In one cohort of 135 patients, the primary endpoint of clinical remission occurred in 26% of those given the novel antibody to tumor necrosis factor–like cytokine 1A (TL1A) vs 1% given placebo (95% CI, 14-37, P < .001). In a smaller cohort of 43 patients genetically pretested for likely response to the new biologic, remission after treatment was only slightly higher at 32% vs 11% (95% CI, 2-38, P = .02).
The incidence of adverse events was similar in both arms, and most events were mild.
The 12-week induction trial, conducted in 14 countries by the ARTEMIS-UC Study Group and led by Bruce E. Sands, MD, MS, AGAF, a professor of medicine at Icahn School of Medicine at Mount Sinai and system chief in the Division of Gastroenterology at Mount Sinai Health System in New York City, was published in The New England Journal of Medicine.
“Our results suggest that important clinical benefit may be achieved through TL1A blockade in patients with UC,” Dr. Sands said in an interview, adding that this is the first rigorous study of a drug class with an entirely new mechanism of action that may be beneficial in other immune-mediated and fibrotic diseases.
“And it is also the first prospective randomized controlled trial in IBD to incorporate a precision-medicine approach using a predictive biomarker for response in a drug development program,” he added.
Dr. Sands stressed the urgent need for new therapies since, despite the approval of multiple new classes of agents, both small molecules and biologics, “there is still a plateau of efficacy in that less than 50% of patients achieve remission at a year.”
He added that UC may progress over time owing to fibrosis of the bowel, a condition not directly or safely addressed by any existing therapies. “Identifying novel targets such as TL1A may allow us to address a different subpopulation of patients who may not respond to the targets addressed by existing therapies,” he said.
In agreement is Jason K. Hou, MD, MS, AGAF, an associate professor of medicine at Baylor College of Medicine and section chief of gastroenterology at Michael E. DeBakey VA Medical Center, both in Houston, Texas. “Although it’s a very exciting time with more options in the last few years for treating UC, even inhibitors with new agents such as JAK inhibitors and interleukin 23 antagonists, many patients have no or only a partial response,” he said in an interview. “Targeting molecules, which has been studied for decades, may offer more than a shot in the dark.”
Why Target TL1A?
Genome-wide studies have shown elevated TL1A, a member of the tumor necrosis factor superfamily, in patients with inflammatory bowel disease (IBD).
“The interaction of TL1A and its ligand, death domain receptor 3, contributes to the immune-mediated inflammation and fibrosis seen in IBD through the downstream production of proinflammatory cytokines by multiple different immune cells, and the elaboration of collagen by fibroblasts,” Dr. Sands explained.
With the intention of targeting TL1A, his group randomly assigned patients with moderate to severe active UC who were glucocorticoid dependent or had not responded to conventional or advanced therapies, with disease extending a minimum of 15 cm from the anal verge. Across arms, the age of the mainly White, non-Hispanic participants ranged from about 37 to about 42, 35%-53% were female, and disease duration was approximately 6-8 years.
The arms received either placebo or intravenous tulisokibart at 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10. Cohort 1 included patients regardless of biomarker status for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response.
Dr. Hou was surprised that response to tulisokibart vs placebo was not greater in test-identified probable responders. “The biomarker didn’t make a huge difference, just a numerical one,” he said. “It may be that more genes are involved than the test could identify, and response is more complicated. Or perhaps the placebo response was particularly high in this small group. We need a deeper dive into why.”
Earlier Application?
“This was a phase 2 study, so it’s too soon to say if tulisokibart could be used as early therapy or in severe disease,” Sands said. “However, the excellent safety profile and efficacy suggest that these populations should be explored in later studies.
Further work is needed to validate the test to predict higher likelihood of response, he added, and recruiting for a phase 3 study is now underway.
The study was supported by Prometheus Biosciences, a subsidiary of Merck. Dr. Sands disclosed multiple ties to private companies, including research support, consulting, data safety monitoring, travel, a gift, and a stock option. Several coauthors reported, variously, research support from and/or consulting for multiple private companies. Others reported employment, variously, with Prometheus and/or Merck, Spyre Therapeutics, and Mirador Therapeutics, or patent holding for IBD drugs. Dr. Hou had no relevant competing interests to disclose but will participate in the phase 3 trial.
A version of this article appeared on Medscape.com.
In one cohort of 135 patients, the primary endpoint of clinical remission occurred in 26% of those given the novel antibody to tumor necrosis factor–like cytokine 1A (TL1A) vs 1% given placebo (95% CI, 14-37, P < .001). In a smaller cohort of 43 patients genetically pretested for likely response to the new biologic, remission after treatment was only slightly higher at 32% vs 11% (95% CI, 2-38, P = .02).
The incidence of adverse events was similar in both arms, and most events were mild.
The 12-week induction trial, conducted in 14 countries by the ARTEMIS-UC Study Group and led by Bruce E. Sands, MD, MS, AGAF, a professor of medicine at Icahn School of Medicine at Mount Sinai and system chief in the Division of Gastroenterology at Mount Sinai Health System in New York City, was published in The New England Journal of Medicine.
“Our results suggest that important clinical benefit may be achieved through TL1A blockade in patients with UC,” Dr. Sands said in an interview, adding that this is the first rigorous study of a drug class with an entirely new mechanism of action that may be beneficial in other immune-mediated and fibrotic diseases.
“And it is also the first prospective randomized controlled trial in IBD to incorporate a precision-medicine approach using a predictive biomarker for response in a drug development program,” he added.
Dr. Sands stressed the urgent need for new therapies since, despite the approval of multiple new classes of agents, both small molecules and biologics, “there is still a plateau of efficacy in that less than 50% of patients achieve remission at a year.”
He added that UC may progress over time owing to fibrosis of the bowel, a condition not directly or safely addressed by any existing therapies. “Identifying novel targets such as TL1A may allow us to address a different subpopulation of patients who may not respond to the targets addressed by existing therapies,” he said.
In agreement is Jason K. Hou, MD, MS, AGAF, an associate professor of medicine at Baylor College of Medicine and section chief of gastroenterology at Michael E. DeBakey VA Medical Center, both in Houston, Texas. “Although it’s a very exciting time with more options in the last few years for treating UC, even inhibitors with new agents such as JAK inhibitors and interleukin 23 antagonists, many patients have no or only a partial response,” he said in an interview. “Targeting molecules, which has been studied for decades, may offer more than a shot in the dark.”
Why Target TL1A?
Genome-wide studies have shown elevated TL1A, a member of the tumor necrosis factor superfamily, in patients with inflammatory bowel disease (IBD).
“The interaction of TL1A and its ligand, death domain receptor 3, contributes to the immune-mediated inflammation and fibrosis seen in IBD through the downstream production of proinflammatory cytokines by multiple different immune cells, and the elaboration of collagen by fibroblasts,” Dr. Sands explained.
With the intention of targeting TL1A, his group randomly assigned patients with moderate to severe active UC who were glucocorticoid dependent or had not responded to conventional or advanced therapies, with disease extending a minimum of 15 cm from the anal verge. Across arms, the age of the mainly White, non-Hispanic participants ranged from about 37 to about 42, 35%-53% were female, and disease duration was approximately 6-8 years.
The arms received either placebo or intravenous tulisokibart at 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10. Cohort 1 included patients regardless of biomarker status for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response.
Dr. Hou was surprised that response to tulisokibart vs placebo was not greater in test-identified probable responders. “The biomarker didn’t make a huge difference, just a numerical one,” he said. “It may be that more genes are involved than the test could identify, and response is more complicated. Or perhaps the placebo response was particularly high in this small group. We need a deeper dive into why.”
Earlier Application?
“This was a phase 2 study, so it’s too soon to say if tulisokibart could be used as early therapy or in severe disease,” Sands said. “However, the excellent safety profile and efficacy suggest that these populations should be explored in later studies.
Further work is needed to validate the test to predict higher likelihood of response, he added, and recruiting for a phase 3 study is now underway.
The study was supported by Prometheus Biosciences, a subsidiary of Merck. Dr. Sands disclosed multiple ties to private companies, including research support, consulting, data safety monitoring, travel, a gift, and a stock option. Several coauthors reported, variously, research support from and/or consulting for multiple private companies. Others reported employment, variously, with Prometheus and/or Merck, Spyre Therapeutics, and Mirador Therapeutics, or patent holding for IBD drugs. Dr. Hou had no relevant competing interests to disclose but will participate in the phase 3 trial.
A version of this article appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Environmental Pollutants Play a Growing Role in IBD
The culprit environmental substances include heavy and transition metals, air pollutants, pesticides, and industrial contaminants. The latter encompass synthetic chemicals such as perfluoroalkyls and polyfluoroalkyls (PFAs), which are present in many common household products.
In contrast, zinc exposure may have a protective, anti-inflammatory effect, according to a research group led by Maria Manuela Estevinho, MD, of the Department of Gastroenterology of the Unidade Local de Saúde Gaia e Espinho in Vila Nova de Gaia, Portugal.
Published in Gut , the review also found limited data suggesting adverse IBD outcomes such as hospitalizations are more prevalent with increased exposure to air contaminants in particular.
“These data carry relevance toward counseling patients and family members,” coauthor Manasi Agrawal, MD, assistant professor of medicine at the Icahn School of Medicine, Mount Sinai, and a gastroenterologist at Mount Sinai Hospital in New York City, said in an interview. “At the individual level, we can try to decrease our exposure to chemicals; for example, to minimize use of pesticides and products containing in our homes. However, at the broader community level, health policy changes are needed to help with mitigation strategies and curb production.”
The physiological mechanisms by which pollutants raise IBD risk include an exaggerated immune response leading to systemic inflammation, loss of tight junction proteins leading to increased gut permeability, and dysbiosis of the intestinal microbiota.
The review found the following effects for various pollutants:
- Heavy and transition metals such as copper, lead, and cadmium were associated with gut dysbiosis, overgrowth of undesirable species of microorganisms, and loss of tight junction proteins leading to leaky gut. In all studies, individuals with IBD showed higher concentrations of such metals than healthy control individuals. While the specific profile of heavy metals varied across studies, lead, copper, and iron, were linked to IBD risk in more than one study.
- The particulate matter present in air pollution — including agricultural and wood dust as well as volcanic ash and hydrocarbon dioxin — was linked to dysbiosis and tight junction protein loss. Air pollution has also been linked to increased incidence of irritable bowel syndrome.
- Industrial and organic pollutants such as perfluoroalkyl and polyfluoroalkyl compounds, triclocarban, and polychlorinated biphenyls were also associated with gut permeability and/or reduced microbial diversity.
- Pesticides such as PFAs, organochloride and organophosphate compounds, and pyrethroids were associated with loss of tight junction proteins.
- Zinc was linked to an increase in tight junction proteins.
Commenting on the review but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MD, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital, and associate professor at Harvard Medical School in Boston, called it a very important study that expands our understanding of the role of environment in IBD.
“While traditionally studies have focused on dietary and other exposures related to personal behavior and lifestyle such as smoking, this expands consideration to exposures at the environmental level, where an individual may have less control,” he said in an interview.
“This shift could be critically important from a policy standpoint as modifying these risk factors may require more societal than individual efforts,” he added. He did offer a caveat, however. “While the review highlights several plausible associations, all of which merit further study, importantly, one should also avoid overinterpreting the results as there are very few high-quality studies that provide robust evidence of an association. So more work is needed.”
Recent research has suggested that environmental exposures affect IBD risk more than genetic predisposition.
As background to this review, the growing industrialization and consumerism of the developing world has seen the global number of IBD cases rise from 3.3 million in 1990 to an estimated 4.9 million in 2019, a jump of 47.5%. In the United States, IBD accounts for more than $25 billion in direct healthcare costs.
In terms of the near future, Dr. Agrawal said, “Next steps would be to measure various chemicals in pre-disease biological samples for objective assessment of the impact of chemicals on IBD risk, and such studies are already underway.”
That would mean using exposure biomarkers with high temporal resolution in preclinical samples, as well as advanced measurement techniques and machine-based composite data analysis to explain the IBD-pollutant relationship. “This approach may also provide insight into the role of different environmental insults in different stages of life and clarify whether the timing of exposure may be more critical than the duration,” the authors wrote.
Dr. Agrawal was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the International Organization For the Study of Inflammatory Bowel Disease, and the Crohn’s and Colitis Foundation. She reported consulting for Douglas Pharmaceuticals. Other authors reported lecture/consulting fees from multiple pharmaceutical/biomedical companies. Dr. Ananthakrishnan had no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
The culprit environmental substances include heavy and transition metals, air pollutants, pesticides, and industrial contaminants. The latter encompass synthetic chemicals such as perfluoroalkyls and polyfluoroalkyls (PFAs), which are present in many common household products.
In contrast, zinc exposure may have a protective, anti-inflammatory effect, according to a research group led by Maria Manuela Estevinho, MD, of the Department of Gastroenterology of the Unidade Local de Saúde Gaia e Espinho in Vila Nova de Gaia, Portugal.
Published in Gut , the review also found limited data suggesting adverse IBD outcomes such as hospitalizations are more prevalent with increased exposure to air contaminants in particular.
“These data carry relevance toward counseling patients and family members,” coauthor Manasi Agrawal, MD, assistant professor of medicine at the Icahn School of Medicine, Mount Sinai, and a gastroenterologist at Mount Sinai Hospital in New York City, said in an interview. “At the individual level, we can try to decrease our exposure to chemicals; for example, to minimize use of pesticides and products containing in our homes. However, at the broader community level, health policy changes are needed to help with mitigation strategies and curb production.”
The physiological mechanisms by which pollutants raise IBD risk include an exaggerated immune response leading to systemic inflammation, loss of tight junction proteins leading to increased gut permeability, and dysbiosis of the intestinal microbiota.
The review found the following effects for various pollutants:
- Heavy and transition metals such as copper, lead, and cadmium were associated with gut dysbiosis, overgrowth of undesirable species of microorganisms, and loss of tight junction proteins leading to leaky gut. In all studies, individuals with IBD showed higher concentrations of such metals than healthy control individuals. While the specific profile of heavy metals varied across studies, lead, copper, and iron, were linked to IBD risk in more than one study.
- The particulate matter present in air pollution — including agricultural and wood dust as well as volcanic ash and hydrocarbon dioxin — was linked to dysbiosis and tight junction protein loss. Air pollution has also been linked to increased incidence of irritable bowel syndrome.
- Industrial and organic pollutants such as perfluoroalkyl and polyfluoroalkyl compounds, triclocarban, and polychlorinated biphenyls were also associated with gut permeability and/or reduced microbial diversity.
- Pesticides such as PFAs, organochloride and organophosphate compounds, and pyrethroids were associated with loss of tight junction proteins.
- Zinc was linked to an increase in tight junction proteins.
Commenting on the review but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MD, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital, and associate professor at Harvard Medical School in Boston, called it a very important study that expands our understanding of the role of environment in IBD.
“While traditionally studies have focused on dietary and other exposures related to personal behavior and lifestyle such as smoking, this expands consideration to exposures at the environmental level, where an individual may have less control,” he said in an interview.
“This shift could be critically important from a policy standpoint as modifying these risk factors may require more societal than individual efforts,” he added. He did offer a caveat, however. “While the review highlights several plausible associations, all of which merit further study, importantly, one should also avoid overinterpreting the results as there are very few high-quality studies that provide robust evidence of an association. So more work is needed.”
Recent research has suggested that environmental exposures affect IBD risk more than genetic predisposition.
As background to this review, the growing industrialization and consumerism of the developing world has seen the global number of IBD cases rise from 3.3 million in 1990 to an estimated 4.9 million in 2019, a jump of 47.5%. In the United States, IBD accounts for more than $25 billion in direct healthcare costs.
In terms of the near future, Dr. Agrawal said, “Next steps would be to measure various chemicals in pre-disease biological samples for objective assessment of the impact of chemicals on IBD risk, and such studies are already underway.”
That would mean using exposure biomarkers with high temporal resolution in preclinical samples, as well as advanced measurement techniques and machine-based composite data analysis to explain the IBD-pollutant relationship. “This approach may also provide insight into the role of different environmental insults in different stages of life and clarify whether the timing of exposure may be more critical than the duration,” the authors wrote.
Dr. Agrawal was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the International Organization For the Study of Inflammatory Bowel Disease, and the Crohn’s and Colitis Foundation. She reported consulting for Douglas Pharmaceuticals. Other authors reported lecture/consulting fees from multiple pharmaceutical/biomedical companies. Dr. Ananthakrishnan had no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
The culprit environmental substances include heavy and transition metals, air pollutants, pesticides, and industrial contaminants. The latter encompass synthetic chemicals such as perfluoroalkyls and polyfluoroalkyls (PFAs), which are present in many common household products.
In contrast, zinc exposure may have a protective, anti-inflammatory effect, according to a research group led by Maria Manuela Estevinho, MD, of the Department of Gastroenterology of the Unidade Local de Saúde Gaia e Espinho in Vila Nova de Gaia, Portugal.
Published in Gut , the review also found limited data suggesting adverse IBD outcomes such as hospitalizations are more prevalent with increased exposure to air contaminants in particular.
“These data carry relevance toward counseling patients and family members,” coauthor Manasi Agrawal, MD, assistant professor of medicine at the Icahn School of Medicine, Mount Sinai, and a gastroenterologist at Mount Sinai Hospital in New York City, said in an interview. “At the individual level, we can try to decrease our exposure to chemicals; for example, to minimize use of pesticides and products containing in our homes. However, at the broader community level, health policy changes are needed to help with mitigation strategies and curb production.”
The physiological mechanisms by which pollutants raise IBD risk include an exaggerated immune response leading to systemic inflammation, loss of tight junction proteins leading to increased gut permeability, and dysbiosis of the intestinal microbiota.
The review found the following effects for various pollutants:
- Heavy and transition metals such as copper, lead, and cadmium were associated with gut dysbiosis, overgrowth of undesirable species of microorganisms, and loss of tight junction proteins leading to leaky gut. In all studies, individuals with IBD showed higher concentrations of such metals than healthy control individuals. While the specific profile of heavy metals varied across studies, lead, copper, and iron, were linked to IBD risk in more than one study.
- The particulate matter present in air pollution — including agricultural and wood dust as well as volcanic ash and hydrocarbon dioxin — was linked to dysbiosis and tight junction protein loss. Air pollution has also been linked to increased incidence of irritable bowel syndrome.
- Industrial and organic pollutants such as perfluoroalkyl and polyfluoroalkyl compounds, triclocarban, and polychlorinated biphenyls were also associated with gut permeability and/or reduced microbial diversity.
- Pesticides such as PFAs, organochloride and organophosphate compounds, and pyrethroids were associated with loss of tight junction proteins.
- Zinc was linked to an increase in tight junction proteins.
Commenting on the review but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MD, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital, and associate professor at Harvard Medical School in Boston, called it a very important study that expands our understanding of the role of environment in IBD.
“While traditionally studies have focused on dietary and other exposures related to personal behavior and lifestyle such as smoking, this expands consideration to exposures at the environmental level, where an individual may have less control,” he said in an interview.
“This shift could be critically important from a policy standpoint as modifying these risk factors may require more societal than individual efforts,” he added. He did offer a caveat, however. “While the review highlights several plausible associations, all of which merit further study, importantly, one should also avoid overinterpreting the results as there are very few high-quality studies that provide robust evidence of an association. So more work is needed.”
Recent research has suggested that environmental exposures affect IBD risk more than genetic predisposition.
As background to this review, the growing industrialization and consumerism of the developing world has seen the global number of IBD cases rise from 3.3 million in 1990 to an estimated 4.9 million in 2019, a jump of 47.5%. In the United States, IBD accounts for more than $25 billion in direct healthcare costs.
In terms of the near future, Dr. Agrawal said, “Next steps would be to measure various chemicals in pre-disease biological samples for objective assessment of the impact of chemicals on IBD risk, and such studies are already underway.”
That would mean using exposure biomarkers with high temporal resolution in preclinical samples, as well as advanced measurement techniques and machine-based composite data analysis to explain the IBD-pollutant relationship. “This approach may also provide insight into the role of different environmental insults in different stages of life and clarify whether the timing of exposure may be more critical than the duration,” the authors wrote.
Dr. Agrawal was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the International Organization For the Study of Inflammatory Bowel Disease, and the Crohn’s and Colitis Foundation. She reported consulting for Douglas Pharmaceuticals. Other authors reported lecture/consulting fees from multiple pharmaceutical/biomedical companies. Dr. Ananthakrishnan had no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Doulas Support Moms-to-Be and Try to Fit Into the Obstetric Care Team
It’s well known that the United States enjoys the dubious distinction of having the worst maternal morbidity and mortality rates among industrialized nations. Maternal mortality in this country increased by 14% from 2018 to 2020, according to the Centers for Disease Control and Prevention’s National Center for Health Statistics.
But a current trend of engaging birth doulas — nonmedical guides offering continuous one-on-one physical and psychological support in the pre-, peri,- and postnatal periods — may be poised to brighten that dismal statistical landscape.
Recent research has shown that mothers matched with a doula are less likely to have a low birth weight baby, less likely to experience a birth complication, and significantly more likely to initiate breastfeeding.
Doula services — even delivered digitally — are seen to lower healthcare costs, reduce cesarean sections, decrease maternal anxiety and depression, and improve communication between healthcare providers and low-income, racially/ethnically diverse pregnant women. Doulas can be especially helpful for mothers dealing with the psychological fallout of miscarriage or stillbirth. They can guide patients in the postpartum period, when problems can arise and when some mothers are lost to medical follow-up, and provide an ongoing source of patient information for the ob.gyn.
“Research has shown that in addition to better outcomes, doula care can shorten labor time and increase patient satisfaction,” said ob.gyn. Layan Alrahmani, MD, in an interview. A maternal-fetal medicine specialist with a focus on high-risk pregnancies among low-income women at Loyola Medicine in Maywood, Illinois, Dr. Alrahmani welcomes doulas to her patients’ antenatal visits.
“Many of my patients who are looking to avoid an epidural will work with a labor doula, in order to stay home as long as possible and to have one-on-one coaching through the pain as things progress,” said Susan Rothenberg, MD, an assistant professor of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai and an ob/gyn at Mount Sinai Downtown Union Square in New York City. She added, “When a woman’s partner is squeamish or potentially unavailable, a labor doula can be a great option.”
Another ob.gyn. who enthusiastically embraces doula care is L. Joy Baker, MD, who practices in LaGrange, Georgia, and is affiliated with Wellstar West Georgia Medical Center. “I love it when my patients have a doula. A doula answers a patient’s questions throughout the pregnancy and amplifies the mother’s voice in the medical system and the clinical setting,” Dr. Baker told this news organization.
“They provide important details on patients’ food, housing, and transportation status when the mothers themselves would not bring those up in a short appointment with their doctors,” she said. Dr. Baker called for more recognition of their merit, especially for first-time and high-risk moms.
Efua B. Leke, MD, MPH, an assistant professor at Baylor College of Medicine and chief of obstetrics at Ben Taub Hospital in Houston, Texas, also believes a major benefit of doulas is improved flow of information. “We know that having doulas participate in maternal care can ease communication between pregnant and parturient mothers and their clinical team,” Dr. Leke said. “This is especially important for under-resourced pregnant women for whom morbidity tends to be disparately higher.”
Doulas can also take pressure off embattled ob.gyn. clinical staff. “Our volume of patients is huge, so we have to keep appointments brief,” Dr. Baker said. “The US is currently 8000 ob.gyn.s short, and to make matters worse, we’re seeing more and more obstetrical care deserts.”
Still largely underutilized, doula care is seen by its proponents as important in light of the drastic shortage of ob.gyn.s and the shrinking presence of maternity care in many US counties.
According to a recent March of Dimes report, access to maternity care is waning, with more than 35% of US counties offering no community obstetrical care and 52% providing no maternity care in local hospitals. That translates to long distances and extended travel time for mothers seeking care.
Growth Remains Slow
Although many believe doulas could become part of the solution to the lack of access to maternity care, their acceptance seems to be slow growing. In a 2012 national survey by Declercq and associates, about 6% of mothers used a doula during childbirth, up from 3% in a 2006 national survey. Of those who were familiar with but lacking doula care, just 27% would have chosen to have this service.
“I’d estimate that doulas are still involved in only about 6%-8% of births,” said Shaconna Haley, MA, a certified holistic doula and doula trainer in Atlanta, Georgia.
And are there enough practicing doulas in the United States to put a dent in the current shortfall in pregnancy care? Although no reliable estimate of their numbers exists, a centralized online doula registration service listed 9000 registered practitioners in 2018. Contrast that with the approximately 3.6 million live births in 2023.
Potential for Friction?
Although generally seen as benign and helpful, the presence of a doula can add another layer of people for hard-pressed medical staff to deal with. Can their attendance occasionally lead to an adversarial encounter? Yes, said Dr. Baker, especially in the case of assertive questioning or suggestions directed at medical staff. “There can be some mistrust on the part of clinicians when nonmedical persons start raising concerns and asking questions. Staff can get a little prickly at this.”
In the view of Melissa A. Simon, MD, MPH, a professor of obstetrics and gynecology, preventive medicine, and medical social sciences at Northwestern University Feinberg School of Medicine in Chicago, Illinois, simple, preventable communication breakdown is often the cause of occasional antagonism. “As in all team care approaches, it’s helpful to have upfront conversations with the birthing person, the doula, and any care team members or support people who will be present in the birthing room. These conversations should be about expectations.”
According to Ms. Haley, “As long as the focus stays firmly on the client/patient and not on the other team members, there should be no friction. Medical staff should be aware there will be a doula in attendance and ideally there should be a collaborative team and plan in place before the birth.”
In Dr. Leke’s experience, doulas do not hinder the medical team as long as clinical roles are well clarified and the patient is engaged in her care plan. “Friction can occur when doulas are functioning outside of their scope of practice, such as speaking to the healthcare team on behalf of the mother instead empowering the mother to speak up herself,” she said. “Or, when the healthcare team doesn’t understand the doula’s scope of practice or recognize the doula as a member of the team.”
Added Dr. Rothenberg, “I’ve occasionally run into doulas who imagine I have an ulterior motive when making recommendations to patients when that’s completely untrue. It’s common for women to decide to become doulas because they didn’t feel listened to during their own birthing experience, and for a few of them, it’s hard to not project that onto their clients’ labor situations, creating conflict where it doesn’t need to exist.”
Barriers and Challenges
Unfortunately, the barriers of cost and access remain high for pregnant and birthing mothers from lower socioeconomic echelons who have no or limited insurance. “There also are very few multilingual doulas or doulas from diverse racial-ethnic backgrounds and identities,” Dr. Simon pointed out.
Yet by all indications, Medicaid members who receive doula services experience positive maternal outcomes, even those at higher risk for pregnancy complications.
As for Medicaid coverage of doula services, in a recent Centers for Medicare & Medicaid Services report, just 11 state Medicaid programs were reimbursing doula services, whereas an additional five were in the process of implementing reimbursement.
Doula care is not covered by all private insurance plans either, Dr. Simon said. “Although there are maternity care bundles with payment models that help integrate doula care, and there are ways to use your flexible spending account to cover it.”
Some hospitals may undertake independent initiatives. Dr. Baker’s center is offering antenatal and peripartum doula support for under-resourced mothers thanks to a Health Resources and Services Administration grant.*
But for now, doula services are largely limited to middle- and high-income women able to afford the associated out-of-pocket costs. These mothers are disproportionately White, and the doulas serving them tend to be of the same race and socioeconomic class.
The Future
Dr. Simon foresees an optimal scenario in which a team of doulas works with all birthing persons on a hospital labor floor as well as with a team of clinicians. “It takes a true team approach to ensure an optimal birthing experience and optimal birth outcomes,” she said.
Despite the many challenges ahead, doulas will probably become a permanent fixture in pregnancy, birth, and postpartum care, said Dr. Baker. “Doula care is going to be a game changer, and obstetricians welcome doulas to the obstetrical care team.”
Dr. Alrahmani, Dr. Baker, Ms. Haley, Dr. Leke, Dr. Rothenberg, and Dr. Simon declared no conflicts of interest relevant to their comments.
*This story was updated on October 1, 2024.
A version of this article first appeared on Medscape.com.
It’s well known that the United States enjoys the dubious distinction of having the worst maternal morbidity and mortality rates among industrialized nations. Maternal mortality in this country increased by 14% from 2018 to 2020, according to the Centers for Disease Control and Prevention’s National Center for Health Statistics.
But a current trend of engaging birth doulas — nonmedical guides offering continuous one-on-one physical and psychological support in the pre-, peri,- and postnatal periods — may be poised to brighten that dismal statistical landscape.
Recent research has shown that mothers matched with a doula are less likely to have a low birth weight baby, less likely to experience a birth complication, and significantly more likely to initiate breastfeeding.
Doula services — even delivered digitally — are seen to lower healthcare costs, reduce cesarean sections, decrease maternal anxiety and depression, and improve communication between healthcare providers and low-income, racially/ethnically diverse pregnant women. Doulas can be especially helpful for mothers dealing with the psychological fallout of miscarriage or stillbirth. They can guide patients in the postpartum period, when problems can arise and when some mothers are lost to medical follow-up, and provide an ongoing source of patient information for the ob.gyn.
“Research has shown that in addition to better outcomes, doula care can shorten labor time and increase patient satisfaction,” said ob.gyn. Layan Alrahmani, MD, in an interview. A maternal-fetal medicine specialist with a focus on high-risk pregnancies among low-income women at Loyola Medicine in Maywood, Illinois, Dr. Alrahmani welcomes doulas to her patients’ antenatal visits.
“Many of my patients who are looking to avoid an epidural will work with a labor doula, in order to stay home as long as possible and to have one-on-one coaching through the pain as things progress,” said Susan Rothenberg, MD, an assistant professor of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai and an ob/gyn at Mount Sinai Downtown Union Square in New York City. She added, “When a woman’s partner is squeamish or potentially unavailable, a labor doula can be a great option.”
Another ob.gyn. who enthusiastically embraces doula care is L. Joy Baker, MD, who practices in LaGrange, Georgia, and is affiliated with Wellstar West Georgia Medical Center. “I love it when my patients have a doula. A doula answers a patient’s questions throughout the pregnancy and amplifies the mother’s voice in the medical system and the clinical setting,” Dr. Baker told this news organization.
“They provide important details on patients’ food, housing, and transportation status when the mothers themselves would not bring those up in a short appointment with their doctors,” she said. Dr. Baker called for more recognition of their merit, especially for first-time and high-risk moms.
Efua B. Leke, MD, MPH, an assistant professor at Baylor College of Medicine and chief of obstetrics at Ben Taub Hospital in Houston, Texas, also believes a major benefit of doulas is improved flow of information. “We know that having doulas participate in maternal care can ease communication between pregnant and parturient mothers and their clinical team,” Dr. Leke said. “This is especially important for under-resourced pregnant women for whom morbidity tends to be disparately higher.”
Doulas can also take pressure off embattled ob.gyn. clinical staff. “Our volume of patients is huge, so we have to keep appointments brief,” Dr. Baker said. “The US is currently 8000 ob.gyn.s short, and to make matters worse, we’re seeing more and more obstetrical care deserts.”
Still largely underutilized, doula care is seen by its proponents as important in light of the drastic shortage of ob.gyn.s and the shrinking presence of maternity care in many US counties.
According to a recent March of Dimes report, access to maternity care is waning, with more than 35% of US counties offering no community obstetrical care and 52% providing no maternity care in local hospitals. That translates to long distances and extended travel time for mothers seeking care.
Growth Remains Slow
Although many believe doulas could become part of the solution to the lack of access to maternity care, their acceptance seems to be slow growing. In a 2012 national survey by Declercq and associates, about 6% of mothers used a doula during childbirth, up from 3% in a 2006 national survey. Of those who were familiar with but lacking doula care, just 27% would have chosen to have this service.
“I’d estimate that doulas are still involved in only about 6%-8% of births,” said Shaconna Haley, MA, a certified holistic doula and doula trainer in Atlanta, Georgia.
And are there enough practicing doulas in the United States to put a dent in the current shortfall in pregnancy care? Although no reliable estimate of their numbers exists, a centralized online doula registration service listed 9000 registered practitioners in 2018. Contrast that with the approximately 3.6 million live births in 2023.
Potential for Friction?
Although generally seen as benign and helpful, the presence of a doula can add another layer of people for hard-pressed medical staff to deal with. Can their attendance occasionally lead to an adversarial encounter? Yes, said Dr. Baker, especially in the case of assertive questioning or suggestions directed at medical staff. “There can be some mistrust on the part of clinicians when nonmedical persons start raising concerns and asking questions. Staff can get a little prickly at this.”
In the view of Melissa A. Simon, MD, MPH, a professor of obstetrics and gynecology, preventive medicine, and medical social sciences at Northwestern University Feinberg School of Medicine in Chicago, Illinois, simple, preventable communication breakdown is often the cause of occasional antagonism. “As in all team care approaches, it’s helpful to have upfront conversations with the birthing person, the doula, and any care team members or support people who will be present in the birthing room. These conversations should be about expectations.”
According to Ms. Haley, “As long as the focus stays firmly on the client/patient and not on the other team members, there should be no friction. Medical staff should be aware there will be a doula in attendance and ideally there should be a collaborative team and plan in place before the birth.”
In Dr. Leke’s experience, doulas do not hinder the medical team as long as clinical roles are well clarified and the patient is engaged in her care plan. “Friction can occur when doulas are functioning outside of their scope of practice, such as speaking to the healthcare team on behalf of the mother instead empowering the mother to speak up herself,” she said. “Or, when the healthcare team doesn’t understand the doula’s scope of practice or recognize the doula as a member of the team.”
Added Dr. Rothenberg, “I’ve occasionally run into doulas who imagine I have an ulterior motive when making recommendations to patients when that’s completely untrue. It’s common for women to decide to become doulas because they didn’t feel listened to during their own birthing experience, and for a few of them, it’s hard to not project that onto their clients’ labor situations, creating conflict where it doesn’t need to exist.”
Barriers and Challenges
Unfortunately, the barriers of cost and access remain high for pregnant and birthing mothers from lower socioeconomic echelons who have no or limited insurance. “There also are very few multilingual doulas or doulas from diverse racial-ethnic backgrounds and identities,” Dr. Simon pointed out.
Yet by all indications, Medicaid members who receive doula services experience positive maternal outcomes, even those at higher risk for pregnancy complications.
As for Medicaid coverage of doula services, in a recent Centers for Medicare & Medicaid Services report, just 11 state Medicaid programs were reimbursing doula services, whereas an additional five were in the process of implementing reimbursement.
Doula care is not covered by all private insurance plans either, Dr. Simon said. “Although there are maternity care bundles with payment models that help integrate doula care, and there are ways to use your flexible spending account to cover it.”
Some hospitals may undertake independent initiatives. Dr. Baker’s center is offering antenatal and peripartum doula support for under-resourced mothers thanks to a Health Resources and Services Administration grant.*
But for now, doula services are largely limited to middle- and high-income women able to afford the associated out-of-pocket costs. These mothers are disproportionately White, and the doulas serving them tend to be of the same race and socioeconomic class.
The Future
Dr. Simon foresees an optimal scenario in which a team of doulas works with all birthing persons on a hospital labor floor as well as with a team of clinicians. “It takes a true team approach to ensure an optimal birthing experience and optimal birth outcomes,” she said.
Despite the many challenges ahead, doulas will probably become a permanent fixture in pregnancy, birth, and postpartum care, said Dr. Baker. “Doula care is going to be a game changer, and obstetricians welcome doulas to the obstetrical care team.”
Dr. Alrahmani, Dr. Baker, Ms. Haley, Dr. Leke, Dr. Rothenberg, and Dr. Simon declared no conflicts of interest relevant to their comments.
*This story was updated on October 1, 2024.
A version of this article first appeared on Medscape.com.
It’s well known that the United States enjoys the dubious distinction of having the worst maternal morbidity and mortality rates among industrialized nations. Maternal mortality in this country increased by 14% from 2018 to 2020, according to the Centers for Disease Control and Prevention’s National Center for Health Statistics.
But a current trend of engaging birth doulas — nonmedical guides offering continuous one-on-one physical and psychological support in the pre-, peri,- and postnatal periods — may be poised to brighten that dismal statistical landscape.
Recent research has shown that mothers matched with a doula are less likely to have a low birth weight baby, less likely to experience a birth complication, and significantly more likely to initiate breastfeeding.
Doula services — even delivered digitally — are seen to lower healthcare costs, reduce cesarean sections, decrease maternal anxiety and depression, and improve communication between healthcare providers and low-income, racially/ethnically diverse pregnant women. Doulas can be especially helpful for mothers dealing with the psychological fallout of miscarriage or stillbirth. They can guide patients in the postpartum period, when problems can arise and when some mothers are lost to medical follow-up, and provide an ongoing source of patient information for the ob.gyn.
“Research has shown that in addition to better outcomes, doula care can shorten labor time and increase patient satisfaction,” said ob.gyn. Layan Alrahmani, MD, in an interview. A maternal-fetal medicine specialist with a focus on high-risk pregnancies among low-income women at Loyola Medicine in Maywood, Illinois, Dr. Alrahmani welcomes doulas to her patients’ antenatal visits.
“Many of my patients who are looking to avoid an epidural will work with a labor doula, in order to stay home as long as possible and to have one-on-one coaching through the pain as things progress,” said Susan Rothenberg, MD, an assistant professor of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai and an ob/gyn at Mount Sinai Downtown Union Square in New York City. She added, “When a woman’s partner is squeamish or potentially unavailable, a labor doula can be a great option.”
Another ob.gyn. who enthusiastically embraces doula care is L. Joy Baker, MD, who practices in LaGrange, Georgia, and is affiliated with Wellstar West Georgia Medical Center. “I love it when my patients have a doula. A doula answers a patient’s questions throughout the pregnancy and amplifies the mother’s voice in the medical system and the clinical setting,” Dr. Baker told this news organization.
“They provide important details on patients’ food, housing, and transportation status when the mothers themselves would not bring those up in a short appointment with their doctors,” she said. Dr. Baker called for more recognition of their merit, especially for first-time and high-risk moms.
Efua B. Leke, MD, MPH, an assistant professor at Baylor College of Medicine and chief of obstetrics at Ben Taub Hospital in Houston, Texas, also believes a major benefit of doulas is improved flow of information. “We know that having doulas participate in maternal care can ease communication between pregnant and parturient mothers and their clinical team,” Dr. Leke said. “This is especially important for under-resourced pregnant women for whom morbidity tends to be disparately higher.”
Doulas can also take pressure off embattled ob.gyn. clinical staff. “Our volume of patients is huge, so we have to keep appointments brief,” Dr. Baker said. “The US is currently 8000 ob.gyn.s short, and to make matters worse, we’re seeing more and more obstetrical care deserts.”
Still largely underutilized, doula care is seen by its proponents as important in light of the drastic shortage of ob.gyn.s and the shrinking presence of maternity care in many US counties.
According to a recent March of Dimes report, access to maternity care is waning, with more than 35% of US counties offering no community obstetrical care and 52% providing no maternity care in local hospitals. That translates to long distances and extended travel time for mothers seeking care.
Growth Remains Slow
Although many believe doulas could become part of the solution to the lack of access to maternity care, their acceptance seems to be slow growing. In a 2012 national survey by Declercq and associates, about 6% of mothers used a doula during childbirth, up from 3% in a 2006 national survey. Of those who were familiar with but lacking doula care, just 27% would have chosen to have this service.
“I’d estimate that doulas are still involved in only about 6%-8% of births,” said Shaconna Haley, MA, a certified holistic doula and doula trainer in Atlanta, Georgia.
And are there enough practicing doulas in the United States to put a dent in the current shortfall in pregnancy care? Although no reliable estimate of their numbers exists, a centralized online doula registration service listed 9000 registered practitioners in 2018. Contrast that with the approximately 3.6 million live births in 2023.
Potential for Friction?
Although generally seen as benign and helpful, the presence of a doula can add another layer of people for hard-pressed medical staff to deal with. Can their attendance occasionally lead to an adversarial encounter? Yes, said Dr. Baker, especially in the case of assertive questioning or suggestions directed at medical staff. “There can be some mistrust on the part of clinicians when nonmedical persons start raising concerns and asking questions. Staff can get a little prickly at this.”
In the view of Melissa A. Simon, MD, MPH, a professor of obstetrics and gynecology, preventive medicine, and medical social sciences at Northwestern University Feinberg School of Medicine in Chicago, Illinois, simple, preventable communication breakdown is often the cause of occasional antagonism. “As in all team care approaches, it’s helpful to have upfront conversations with the birthing person, the doula, and any care team members or support people who will be present in the birthing room. These conversations should be about expectations.”
According to Ms. Haley, “As long as the focus stays firmly on the client/patient and not on the other team members, there should be no friction. Medical staff should be aware there will be a doula in attendance and ideally there should be a collaborative team and plan in place before the birth.”
In Dr. Leke’s experience, doulas do not hinder the medical team as long as clinical roles are well clarified and the patient is engaged in her care plan. “Friction can occur when doulas are functioning outside of their scope of practice, such as speaking to the healthcare team on behalf of the mother instead empowering the mother to speak up herself,” she said. “Or, when the healthcare team doesn’t understand the doula’s scope of practice or recognize the doula as a member of the team.”
Added Dr. Rothenberg, “I’ve occasionally run into doulas who imagine I have an ulterior motive when making recommendations to patients when that’s completely untrue. It’s common for women to decide to become doulas because they didn’t feel listened to during their own birthing experience, and for a few of them, it’s hard to not project that onto their clients’ labor situations, creating conflict where it doesn’t need to exist.”
Barriers and Challenges
Unfortunately, the barriers of cost and access remain high for pregnant and birthing mothers from lower socioeconomic echelons who have no or limited insurance. “There also are very few multilingual doulas or doulas from diverse racial-ethnic backgrounds and identities,” Dr. Simon pointed out.
Yet by all indications, Medicaid members who receive doula services experience positive maternal outcomes, even those at higher risk for pregnancy complications.
As for Medicaid coverage of doula services, in a recent Centers for Medicare & Medicaid Services report, just 11 state Medicaid programs were reimbursing doula services, whereas an additional five were in the process of implementing reimbursement.
Doula care is not covered by all private insurance plans either, Dr. Simon said. “Although there are maternity care bundles with payment models that help integrate doula care, and there are ways to use your flexible spending account to cover it.”
Some hospitals may undertake independent initiatives. Dr. Baker’s center is offering antenatal and peripartum doula support for under-resourced mothers thanks to a Health Resources and Services Administration grant.*
But for now, doula services are largely limited to middle- and high-income women able to afford the associated out-of-pocket costs. These mothers are disproportionately White, and the doulas serving them tend to be of the same race and socioeconomic class.
The Future
Dr. Simon foresees an optimal scenario in which a team of doulas works with all birthing persons on a hospital labor floor as well as with a team of clinicians. “It takes a true team approach to ensure an optimal birthing experience and optimal birth outcomes,” she said.
Despite the many challenges ahead, doulas will probably become a permanent fixture in pregnancy, birth, and postpartum care, said Dr. Baker. “Doula care is going to be a game changer, and obstetricians welcome doulas to the obstetrical care team.”
Dr. Alrahmani, Dr. Baker, Ms. Haley, Dr. Leke, Dr. Rothenberg, and Dr. Simon declared no conflicts of interest relevant to their comments.
*This story was updated on October 1, 2024.
A version of this article first appeared on Medscape.com.
Genitourinary Symptoms in Men: Canaries in the Coal Mine for Underlying Chronic Disease
At age 57, a senior scientific researcher in Santa Barbara, California, complained of chronic erectile dysfunction (ED) in what had been a sexually active marriage. “I just couldn’t get an erection, let alone sustain one. Apart from that, I maybe felt a bit tired but generally okay,” he said. Though seemingly well otherwise, 18 months later he was dead of a hereditary right-sided colon cancer.
While not all cases of ED are associated with a dire outcome, the genitourinary signals of ED and lower urinary tract symptoms (LUTS), especially nocturia, serve as sentinel indicators of the presence of, or risk factors for, serious chronic conditions. These commonly include cardiovascular disease (CVD), diabetes, and metabolic syndrome and are associated with obesity, depression, and obstructive sleep apnea.
Sometimes these serious conditions may stay under the radar until men seek help for ED or LUTS.
“We know that among men who had a heart attack, 50% had some degree of ED within 3 years of their cardiac event,” Sam Tafari, MBBS, of the Endocrine and Metabolic Unit at Royal Adelaide Hospital in Adelaide, South Australia, said in an interview.
That’s the bad news. The good news is that these two problems may specifically incentivize men to seek timely care for serious conditions they might otherwise not get, according to Dr. Tafari. And primary care doctors are ideally positioned to get men early multifaceted care. He recently coauthored a call to action on this issue in a review appearing in the Journal of Men’s Health.
In Dr. Tafari’s experience, most patients seeking urological care are unaware of the multiple conditions linked to ED and LUTS. “Many consider these to be due to issues like low testosterone, which actually make up a very small proportion of cases of ED,” he said. Aging, obesity, inactivity, smoking, alcohol abuse, and prescription and street drugs can also contribute to the development of ED.
In most affected men, ED is of vascular etiology, with endothelial dysfunction of the inner lining of blood vessels and smooth muscle the common denominator.
This dysfunction causes inadequate blood supply to both the coronary and the penile arteries, so ED and CVD are considered different manifestations of the same systemic disorder. Because the tumescence-controlling cavernosal vessels of the penis are considerably smaller, the same level of arteriopathy causes a more severe reduction in blood in the erectile tissue. As a result, ED often precedes CVD and presents an early opportunity to screen men for CVD.
As to the mechanisms behind LUTS, Peter N. Tsambarlis, MD, a urologist at Northwestern Medicine in Chicago, subscribes to the inflammation theory. “Suboptimal health issues such as high [blood] pressure, blood lipids, and blood glucose lead to chronic widespread inflammation, which makes the bladder less flexible as a storage vessel,” he explained. “It’s not able to stretch adequately overnight to hold the urine until morning.”
Ask Early, Ask Often
Jeffrey P. Weiss, MD, PhD, chair of the Department of Urology at SUNY Downstate Health Sciences University in Brooklyn, New York, has done research that uncovered a relationship between structural cardiac disease and nocturia. “So if you had to ask a patient a single question that would point to a global health issue, it would be ‘Do you have frequent nighttime urination,’ ” he said.
It’s never too soon to ask men about these symptoms, said Dr. Tsambarlis. The best time to raise issues of ED and LUTS is when a man enters primary care — regardless of age or absence of symptoms. “That way you have a baseline and can watch for changes and do early intervention as needed. Men don’t usually want to bring up sexual dysfunction or urinary health, but asking doesn’t need to dominate the visit,” he said.
Dr. Tafari recommends that primary care physicians adopt a targeted approach using ED and nocturia as entry points for engaging men in their healthcare. While acknowledging that primary care physicians have an ever-growing checklist of questions to ask patients and hardly need one more thing to screen for, he suggests asking two quick, and easy “before you go” genitourinary queries:
- Are you having trouble with erections or having sex?
- Are you getting up at night to pass urine more than once?
“The men really appreciate being asked,” he said. “But what worries me is all the men we don’t see who have these symptoms but don’t know they’re important, and no one is asking about them.”
Gideon Richards, MD, a urologist at the Northwell Health Physician Partners Smith Institute for Urology at Garden City, and director of Men’s Health, Central Region, for Northwell Health in New Hyde Park, both in New York, said erectile problems should not wait for specialty care. By the time men with ED are referred to urology, they may already have failed treatment with first-line phosphodiesterase 5 inhibitor therapy, he said. “A significant proportion will have arteriogenic erectile dysfunction, a measurable decrease in the amount of blood flow into the erectile bodies.”
Addressing the Issue
Addressing genitourinary-signaled issues has the double benefit of easing ED and LUTS and improving men’s health and longevity and may help narrow the worldwide gender gap in life expectancy. As a recent global analysis found, there’s a 5-year longevity disparity favoring women over men. Biology aside, men do not access healthcare as often as women, who consult their general practitioners regularly throughout their lifespan for multiple reasons, including reproductive care, and more screening programs are aimed at women.
Added Dr. Tsambarlis, “Men should know that losing weight and switching to a healthy lifestyle can improve sexual function about half as much as phosphodiesterase 5 inhibitors such as sildenafil [Viagra] or tadalafil [Cialis].”
“Many, however, would prefer just to take drugs rather than change their lifestyle and lose weight. There are certainly effective options available, but these are not uniformly effective,” said Dr. Weiss.
Dr. Tafari’s group is designing a short, simple, culturally acceptable screening tool for use in primary care practice and will monitor its impact on physician prescribing habits and overall men’s health outcomes.
Dr. Tafari received funding from the Hospital Research Foundation and Freemasons Centre for Male Health and Wellbeing in Adelaide, South Australia. Dr. Tafari, Dr. Tsambarlis, Dr. Weiss, and Dr. Richards had no relevant conflicts of interest to declare.
A version of this article appeared on Medscape.com.
At age 57, a senior scientific researcher in Santa Barbara, California, complained of chronic erectile dysfunction (ED) in what had been a sexually active marriage. “I just couldn’t get an erection, let alone sustain one. Apart from that, I maybe felt a bit tired but generally okay,” he said. Though seemingly well otherwise, 18 months later he was dead of a hereditary right-sided colon cancer.
While not all cases of ED are associated with a dire outcome, the genitourinary signals of ED and lower urinary tract symptoms (LUTS), especially nocturia, serve as sentinel indicators of the presence of, or risk factors for, serious chronic conditions. These commonly include cardiovascular disease (CVD), diabetes, and metabolic syndrome and are associated with obesity, depression, and obstructive sleep apnea.
Sometimes these serious conditions may stay under the radar until men seek help for ED or LUTS.
“We know that among men who had a heart attack, 50% had some degree of ED within 3 years of their cardiac event,” Sam Tafari, MBBS, of the Endocrine and Metabolic Unit at Royal Adelaide Hospital in Adelaide, South Australia, said in an interview.
That’s the bad news. The good news is that these two problems may specifically incentivize men to seek timely care for serious conditions they might otherwise not get, according to Dr. Tafari. And primary care doctors are ideally positioned to get men early multifaceted care. He recently coauthored a call to action on this issue in a review appearing in the Journal of Men’s Health.
In Dr. Tafari’s experience, most patients seeking urological care are unaware of the multiple conditions linked to ED and LUTS. “Many consider these to be due to issues like low testosterone, which actually make up a very small proportion of cases of ED,” he said. Aging, obesity, inactivity, smoking, alcohol abuse, and prescription and street drugs can also contribute to the development of ED.
In most affected men, ED is of vascular etiology, with endothelial dysfunction of the inner lining of blood vessels and smooth muscle the common denominator.
This dysfunction causes inadequate blood supply to both the coronary and the penile arteries, so ED and CVD are considered different manifestations of the same systemic disorder. Because the tumescence-controlling cavernosal vessels of the penis are considerably smaller, the same level of arteriopathy causes a more severe reduction in blood in the erectile tissue. As a result, ED often precedes CVD and presents an early opportunity to screen men for CVD.
As to the mechanisms behind LUTS, Peter N. Tsambarlis, MD, a urologist at Northwestern Medicine in Chicago, subscribes to the inflammation theory. “Suboptimal health issues such as high [blood] pressure, blood lipids, and blood glucose lead to chronic widespread inflammation, which makes the bladder less flexible as a storage vessel,” he explained. “It’s not able to stretch adequately overnight to hold the urine until morning.”
Ask Early, Ask Often
Jeffrey P. Weiss, MD, PhD, chair of the Department of Urology at SUNY Downstate Health Sciences University in Brooklyn, New York, has done research that uncovered a relationship between structural cardiac disease and nocturia. “So if you had to ask a patient a single question that would point to a global health issue, it would be ‘Do you have frequent nighttime urination,’ ” he said.
It’s never too soon to ask men about these symptoms, said Dr. Tsambarlis. The best time to raise issues of ED and LUTS is when a man enters primary care — regardless of age or absence of symptoms. “That way you have a baseline and can watch for changes and do early intervention as needed. Men don’t usually want to bring up sexual dysfunction or urinary health, but asking doesn’t need to dominate the visit,” he said.
Dr. Tafari recommends that primary care physicians adopt a targeted approach using ED and nocturia as entry points for engaging men in their healthcare. While acknowledging that primary care physicians have an ever-growing checklist of questions to ask patients and hardly need one more thing to screen for, he suggests asking two quick, and easy “before you go” genitourinary queries:
- Are you having trouble with erections or having sex?
- Are you getting up at night to pass urine more than once?
“The men really appreciate being asked,” he said. “But what worries me is all the men we don’t see who have these symptoms but don’t know they’re important, and no one is asking about them.”
Gideon Richards, MD, a urologist at the Northwell Health Physician Partners Smith Institute for Urology at Garden City, and director of Men’s Health, Central Region, for Northwell Health in New Hyde Park, both in New York, said erectile problems should not wait for specialty care. By the time men with ED are referred to urology, they may already have failed treatment with first-line phosphodiesterase 5 inhibitor therapy, he said. “A significant proportion will have arteriogenic erectile dysfunction, a measurable decrease in the amount of blood flow into the erectile bodies.”
Addressing the Issue
Addressing genitourinary-signaled issues has the double benefit of easing ED and LUTS and improving men’s health and longevity and may help narrow the worldwide gender gap in life expectancy. As a recent global analysis found, there’s a 5-year longevity disparity favoring women over men. Biology aside, men do not access healthcare as often as women, who consult their general practitioners regularly throughout their lifespan for multiple reasons, including reproductive care, and more screening programs are aimed at women.
Added Dr. Tsambarlis, “Men should know that losing weight and switching to a healthy lifestyle can improve sexual function about half as much as phosphodiesterase 5 inhibitors such as sildenafil [Viagra] or tadalafil [Cialis].”
“Many, however, would prefer just to take drugs rather than change their lifestyle and lose weight. There are certainly effective options available, but these are not uniformly effective,” said Dr. Weiss.
Dr. Tafari’s group is designing a short, simple, culturally acceptable screening tool for use in primary care practice and will monitor its impact on physician prescribing habits and overall men’s health outcomes.
Dr. Tafari received funding from the Hospital Research Foundation and Freemasons Centre for Male Health and Wellbeing in Adelaide, South Australia. Dr. Tafari, Dr. Tsambarlis, Dr. Weiss, and Dr. Richards had no relevant conflicts of interest to declare.
A version of this article appeared on Medscape.com.
At age 57, a senior scientific researcher in Santa Barbara, California, complained of chronic erectile dysfunction (ED) in what had been a sexually active marriage. “I just couldn’t get an erection, let alone sustain one. Apart from that, I maybe felt a bit tired but generally okay,” he said. Though seemingly well otherwise, 18 months later he was dead of a hereditary right-sided colon cancer.
While not all cases of ED are associated with a dire outcome, the genitourinary signals of ED and lower urinary tract symptoms (LUTS), especially nocturia, serve as sentinel indicators of the presence of, or risk factors for, serious chronic conditions. These commonly include cardiovascular disease (CVD), diabetes, and metabolic syndrome and are associated with obesity, depression, and obstructive sleep apnea.
Sometimes these serious conditions may stay under the radar until men seek help for ED or LUTS.
“We know that among men who had a heart attack, 50% had some degree of ED within 3 years of their cardiac event,” Sam Tafari, MBBS, of the Endocrine and Metabolic Unit at Royal Adelaide Hospital in Adelaide, South Australia, said in an interview.
That’s the bad news. The good news is that these two problems may specifically incentivize men to seek timely care for serious conditions they might otherwise not get, according to Dr. Tafari. And primary care doctors are ideally positioned to get men early multifaceted care. He recently coauthored a call to action on this issue in a review appearing in the Journal of Men’s Health.
In Dr. Tafari’s experience, most patients seeking urological care are unaware of the multiple conditions linked to ED and LUTS. “Many consider these to be due to issues like low testosterone, which actually make up a very small proportion of cases of ED,” he said. Aging, obesity, inactivity, smoking, alcohol abuse, and prescription and street drugs can also contribute to the development of ED.
In most affected men, ED is of vascular etiology, with endothelial dysfunction of the inner lining of blood vessels and smooth muscle the common denominator.
This dysfunction causes inadequate blood supply to both the coronary and the penile arteries, so ED and CVD are considered different manifestations of the same systemic disorder. Because the tumescence-controlling cavernosal vessels of the penis are considerably smaller, the same level of arteriopathy causes a more severe reduction in blood in the erectile tissue. As a result, ED often precedes CVD and presents an early opportunity to screen men for CVD.
As to the mechanisms behind LUTS, Peter N. Tsambarlis, MD, a urologist at Northwestern Medicine in Chicago, subscribes to the inflammation theory. “Suboptimal health issues such as high [blood] pressure, blood lipids, and blood glucose lead to chronic widespread inflammation, which makes the bladder less flexible as a storage vessel,” he explained. “It’s not able to stretch adequately overnight to hold the urine until morning.”
Ask Early, Ask Often
Jeffrey P. Weiss, MD, PhD, chair of the Department of Urology at SUNY Downstate Health Sciences University in Brooklyn, New York, has done research that uncovered a relationship between structural cardiac disease and nocturia. “So if you had to ask a patient a single question that would point to a global health issue, it would be ‘Do you have frequent nighttime urination,’ ” he said.
It’s never too soon to ask men about these symptoms, said Dr. Tsambarlis. The best time to raise issues of ED and LUTS is when a man enters primary care — regardless of age or absence of symptoms. “That way you have a baseline and can watch for changes and do early intervention as needed. Men don’t usually want to bring up sexual dysfunction or urinary health, but asking doesn’t need to dominate the visit,” he said.
Dr. Tafari recommends that primary care physicians adopt a targeted approach using ED and nocturia as entry points for engaging men in their healthcare. While acknowledging that primary care physicians have an ever-growing checklist of questions to ask patients and hardly need one more thing to screen for, he suggests asking two quick, and easy “before you go” genitourinary queries:
- Are you having trouble with erections or having sex?
- Are you getting up at night to pass urine more than once?
“The men really appreciate being asked,” he said. “But what worries me is all the men we don’t see who have these symptoms but don’t know they’re important, and no one is asking about them.”
Gideon Richards, MD, a urologist at the Northwell Health Physician Partners Smith Institute for Urology at Garden City, and director of Men’s Health, Central Region, for Northwell Health in New Hyde Park, both in New York, said erectile problems should not wait for specialty care. By the time men with ED are referred to urology, they may already have failed treatment with first-line phosphodiesterase 5 inhibitor therapy, he said. “A significant proportion will have arteriogenic erectile dysfunction, a measurable decrease in the amount of blood flow into the erectile bodies.”
Addressing the Issue
Addressing genitourinary-signaled issues has the double benefit of easing ED and LUTS and improving men’s health and longevity and may help narrow the worldwide gender gap in life expectancy. As a recent global analysis found, there’s a 5-year longevity disparity favoring women over men. Biology aside, men do not access healthcare as often as women, who consult their general practitioners regularly throughout their lifespan for multiple reasons, including reproductive care, and more screening programs are aimed at women.
Added Dr. Tsambarlis, “Men should know that losing weight and switching to a healthy lifestyle can improve sexual function about half as much as phosphodiesterase 5 inhibitors such as sildenafil [Viagra] or tadalafil [Cialis].”
“Many, however, would prefer just to take drugs rather than change their lifestyle and lose weight. There are certainly effective options available, but these are not uniformly effective,” said Dr. Weiss.
Dr. Tafari’s group is designing a short, simple, culturally acceptable screening tool for use in primary care practice and will monitor its impact on physician prescribing habits and overall men’s health outcomes.
Dr. Tafari received funding from the Hospital Research Foundation and Freemasons Centre for Male Health and Wellbeing in Adelaide, South Australia. Dr. Tafari, Dr. Tsambarlis, Dr. Weiss, and Dr. Richards had no relevant conflicts of interest to declare.
A version of this article appeared on Medscape.com.
Time-Restricted Eating Fails for Weight Loss and Glucose Homeostasis
, a small randomized controlled trial found.
The results suggested that any effects of TRE on weight observed in prior studies may be due to reductions in caloric intake and not timing, according to Nisa M. Maruthur, MD, MHS, of the Division of General Internal Medicine at the Johns Hopkins School of Medicine in Baltimore, and colleagues.
Published in Annals of Internal Medicine, the 12-week trial randomly assigned 41 adults aged 18-69 years with obesity and prediabetes or diet-controlled diabetes 1:1 as follows: To TRE, involving a 10-hour eating window with 80% of calories consumed before 1 PM, or to UEP, involving a ≤ 16-hour window, with at least 50% of calories consumed after 5 PM. The regimen in each group was based on the OmniHeart unsaturated fat diet and the SPICE study.
“The diet was similar to the DASH [Dietary Approaches to Stop Hypertension] diet for hypertension and maybe a bit higher in unsaturated fat and micronutrients,” said study co-author Scott J. Pilla, MD, MHS, an assistant professor of medicine at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in an interview. For each participant, macro- and micronutrient content remained constant throughout the study period, with total calories individually determined at baseline and ranging from 1600 to 3500 kcal/d. “That differs from some TRE studies in which calories were adjusted according to whether participants lost or gained weight,” he said. “This was a purely mechanistic study to determine the impact of time of eating alone with no change in calories.”
Although the current findings revealed no weight loss advantage, some evidence suggests that limiting the food consumption window to 4-10 hours naturally reduces energy intake by approximately 200-550 calories per day and can result in a loss of 3%-5% of baseline body weight for 2-12 months. In addition, TRE has been shown to improve metabolic risk factors, such as insulin resistance, blood pressure, and triglyceride concentrations — but not in this study.
The Cohort
The mean age was 59 years, 93% of patients were women, and 93% were Black. The mean body mass index was 36, and the mean baseline weight was 96.2 kg — 95.6 kg in the TRE group and 103.7 kg in the UEP group.
At 12 weeks, weight decreased comparably by 2.3 kg (95% CI, 1.0-3.5) in the TRE group and by 2.6 kg (95% CI, 1.5-3.7) in the UEP group. Change in glycemic measures did not differ between the two groups.
Interestingly, self-reporting questionnaires revealed a slight reduction in physical activity in the TRE group, an effect that requires further study. “We don’t know why but anecdotally, some TRE participants said they tended to go to bed earlier,” Dr. Pilla said. Earlier bedtimes may put an end sooner to the daily eating pattern.
Subanalyses of the data are ongoing and will be published later.
“In the context of several clinical trials that suggest a benefit of TRE, our findings suggest that if or when TRE interventions induce weight loss, it is likely in part due to a reduction in energy intake, and therefore, clinicians can counsel patients that TRE may help them lose weight by decreasing their caloric intake,” the authors wrote.
In an accompanying editorial, Krista A. Varady, PhD, and Vanessa M. Oddo, PhD, of the Department of Kinesiology and Nutrition at the University of Illinois–Chicago, said the study results have important clinical implications. “Many patients stop following standard-care diets (such as daily calorie restriction) because they become frustrated with having to monitor food intake vigilantly each day,” they wrote.
Although TRE is no more effective than other diet interventions for weight reduction, it offers a simplified approach to treat obesity by omitting the need for calorie counting. “TRE bypasses this requirement simply by allowing participants to ‘watch the clock’ instead of monitoring calories, while still producing weight loss,” they wrote.
The straightforward nature of this diet makes it well suited for remote delivery, which can reduce the scheduling and financial barriers associated with inpatient visits, they added. “Moreover, TRE does not require the purchase of expensive food products and allows a person to continue consuming familiar foods, making it a high accessible diet for lower-resource populations.”
Gastroenterologists and Obesity
Of late, support has grown for gastroenterologists to become actively involved in obesity treatment — even to “take ownership” of this field.
In a 2023 article in Gut, Michael Camilleri, MD, AGAF, a gastroenterologist at the Mayo Clinic in Rochester, Minnesota, made the case for the natural fit between gastrointestinal (GI) specialists and obesity management. He noted that obesity is a significant risk factor for GI, pancreatic, and liver diseases. It can even affect inflammatory bowel disease.
“Treating obesity starting when patients present in gastroenterology and hepatology clinics has potential to impact serious consequences of obesity such as cardiovascular risks,” he wrote.
Gastroenterologists already treat GI conditions with pharmacologic and surgical interventions that can also be used to treat obesity and improve glycemic control. These include pancreatic lipase inhibitors and incretin, bariatric endoscopy and surgery, and combination therapies targeting metabolic problems.
This study was supported by the American Heart Association.
Dr. Maruthur reported receiving royalties from a virtual diabetes prevention program. Dr. Pilla reported receiving travel, advisory, and speaker fees from the American Diabetes Association. Numerous authors reported receiving grants from government and nonprofit research funding organizations. Dr. Varady disclosed having no competing interests. Dr. Odda reported receiving research support and honoraria from government nonprofit funding organizations.
A version of this article first appeared on Medscape.com.
, a small randomized controlled trial found.
The results suggested that any effects of TRE on weight observed in prior studies may be due to reductions in caloric intake and not timing, according to Nisa M. Maruthur, MD, MHS, of the Division of General Internal Medicine at the Johns Hopkins School of Medicine in Baltimore, and colleagues.
Published in Annals of Internal Medicine, the 12-week trial randomly assigned 41 adults aged 18-69 years with obesity and prediabetes or diet-controlled diabetes 1:1 as follows: To TRE, involving a 10-hour eating window with 80% of calories consumed before 1 PM, or to UEP, involving a ≤ 16-hour window, with at least 50% of calories consumed after 5 PM. The regimen in each group was based on the OmniHeart unsaturated fat diet and the SPICE study.
“The diet was similar to the DASH [Dietary Approaches to Stop Hypertension] diet for hypertension and maybe a bit higher in unsaturated fat and micronutrients,” said study co-author Scott J. Pilla, MD, MHS, an assistant professor of medicine at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in an interview. For each participant, macro- and micronutrient content remained constant throughout the study period, with total calories individually determined at baseline and ranging from 1600 to 3500 kcal/d. “That differs from some TRE studies in which calories were adjusted according to whether participants lost or gained weight,” he said. “This was a purely mechanistic study to determine the impact of time of eating alone with no change in calories.”
Although the current findings revealed no weight loss advantage, some evidence suggests that limiting the food consumption window to 4-10 hours naturally reduces energy intake by approximately 200-550 calories per day and can result in a loss of 3%-5% of baseline body weight for 2-12 months. In addition, TRE has been shown to improve metabolic risk factors, such as insulin resistance, blood pressure, and triglyceride concentrations — but not in this study.
The Cohort
The mean age was 59 years, 93% of patients were women, and 93% were Black. The mean body mass index was 36, and the mean baseline weight was 96.2 kg — 95.6 kg in the TRE group and 103.7 kg in the UEP group.
At 12 weeks, weight decreased comparably by 2.3 kg (95% CI, 1.0-3.5) in the TRE group and by 2.6 kg (95% CI, 1.5-3.7) in the UEP group. Change in glycemic measures did not differ between the two groups.
Interestingly, self-reporting questionnaires revealed a slight reduction in physical activity in the TRE group, an effect that requires further study. “We don’t know why but anecdotally, some TRE participants said they tended to go to bed earlier,” Dr. Pilla said. Earlier bedtimes may put an end sooner to the daily eating pattern.
Subanalyses of the data are ongoing and will be published later.
“In the context of several clinical trials that suggest a benefit of TRE, our findings suggest that if or when TRE interventions induce weight loss, it is likely in part due to a reduction in energy intake, and therefore, clinicians can counsel patients that TRE may help them lose weight by decreasing their caloric intake,” the authors wrote.
In an accompanying editorial, Krista A. Varady, PhD, and Vanessa M. Oddo, PhD, of the Department of Kinesiology and Nutrition at the University of Illinois–Chicago, said the study results have important clinical implications. “Many patients stop following standard-care diets (such as daily calorie restriction) because they become frustrated with having to monitor food intake vigilantly each day,” they wrote.
Although TRE is no more effective than other diet interventions for weight reduction, it offers a simplified approach to treat obesity by omitting the need for calorie counting. “TRE bypasses this requirement simply by allowing participants to ‘watch the clock’ instead of monitoring calories, while still producing weight loss,” they wrote.
The straightforward nature of this diet makes it well suited for remote delivery, which can reduce the scheduling and financial barriers associated with inpatient visits, they added. “Moreover, TRE does not require the purchase of expensive food products and allows a person to continue consuming familiar foods, making it a high accessible diet for lower-resource populations.”
Gastroenterologists and Obesity
Of late, support has grown for gastroenterologists to become actively involved in obesity treatment — even to “take ownership” of this field.
In a 2023 article in Gut, Michael Camilleri, MD, AGAF, a gastroenterologist at the Mayo Clinic in Rochester, Minnesota, made the case for the natural fit between gastrointestinal (GI) specialists and obesity management. He noted that obesity is a significant risk factor for GI, pancreatic, and liver diseases. It can even affect inflammatory bowel disease.
“Treating obesity starting when patients present in gastroenterology and hepatology clinics has potential to impact serious consequences of obesity such as cardiovascular risks,” he wrote.
Gastroenterologists already treat GI conditions with pharmacologic and surgical interventions that can also be used to treat obesity and improve glycemic control. These include pancreatic lipase inhibitors and incretin, bariatric endoscopy and surgery, and combination therapies targeting metabolic problems.
This study was supported by the American Heart Association.
Dr. Maruthur reported receiving royalties from a virtual diabetes prevention program. Dr. Pilla reported receiving travel, advisory, and speaker fees from the American Diabetes Association. Numerous authors reported receiving grants from government and nonprofit research funding organizations. Dr. Varady disclosed having no competing interests. Dr. Odda reported receiving research support and honoraria from government nonprofit funding organizations.
A version of this article first appeared on Medscape.com.
, a small randomized controlled trial found.
The results suggested that any effects of TRE on weight observed in prior studies may be due to reductions in caloric intake and not timing, according to Nisa M. Maruthur, MD, MHS, of the Division of General Internal Medicine at the Johns Hopkins School of Medicine in Baltimore, and colleagues.
Published in Annals of Internal Medicine, the 12-week trial randomly assigned 41 adults aged 18-69 years with obesity and prediabetes or diet-controlled diabetes 1:1 as follows: To TRE, involving a 10-hour eating window with 80% of calories consumed before 1 PM, or to UEP, involving a ≤ 16-hour window, with at least 50% of calories consumed after 5 PM. The regimen in each group was based on the OmniHeart unsaturated fat diet and the SPICE study.
“The diet was similar to the DASH [Dietary Approaches to Stop Hypertension] diet for hypertension and maybe a bit higher in unsaturated fat and micronutrients,” said study co-author Scott J. Pilla, MD, MHS, an assistant professor of medicine at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in an interview. For each participant, macro- and micronutrient content remained constant throughout the study period, with total calories individually determined at baseline and ranging from 1600 to 3500 kcal/d. “That differs from some TRE studies in which calories were adjusted according to whether participants lost or gained weight,” he said. “This was a purely mechanistic study to determine the impact of time of eating alone with no change in calories.”
Although the current findings revealed no weight loss advantage, some evidence suggests that limiting the food consumption window to 4-10 hours naturally reduces energy intake by approximately 200-550 calories per day and can result in a loss of 3%-5% of baseline body weight for 2-12 months. In addition, TRE has been shown to improve metabolic risk factors, such as insulin resistance, blood pressure, and triglyceride concentrations — but not in this study.
The Cohort
The mean age was 59 years, 93% of patients were women, and 93% were Black. The mean body mass index was 36, and the mean baseline weight was 96.2 kg — 95.6 kg in the TRE group and 103.7 kg in the UEP group.
At 12 weeks, weight decreased comparably by 2.3 kg (95% CI, 1.0-3.5) in the TRE group and by 2.6 kg (95% CI, 1.5-3.7) in the UEP group. Change in glycemic measures did not differ between the two groups.
Interestingly, self-reporting questionnaires revealed a slight reduction in physical activity in the TRE group, an effect that requires further study. “We don’t know why but anecdotally, some TRE participants said they tended to go to bed earlier,” Dr. Pilla said. Earlier bedtimes may put an end sooner to the daily eating pattern.
Subanalyses of the data are ongoing and will be published later.
“In the context of several clinical trials that suggest a benefit of TRE, our findings suggest that if or when TRE interventions induce weight loss, it is likely in part due to a reduction in energy intake, and therefore, clinicians can counsel patients that TRE may help them lose weight by decreasing their caloric intake,” the authors wrote.
In an accompanying editorial, Krista A. Varady, PhD, and Vanessa M. Oddo, PhD, of the Department of Kinesiology and Nutrition at the University of Illinois–Chicago, said the study results have important clinical implications. “Many patients stop following standard-care diets (such as daily calorie restriction) because they become frustrated with having to monitor food intake vigilantly each day,” they wrote.
Although TRE is no more effective than other diet interventions for weight reduction, it offers a simplified approach to treat obesity by omitting the need for calorie counting. “TRE bypasses this requirement simply by allowing participants to ‘watch the clock’ instead of monitoring calories, while still producing weight loss,” they wrote.
The straightforward nature of this diet makes it well suited for remote delivery, which can reduce the scheduling and financial barriers associated with inpatient visits, they added. “Moreover, TRE does not require the purchase of expensive food products and allows a person to continue consuming familiar foods, making it a high accessible diet for lower-resource populations.”
Gastroenterologists and Obesity
Of late, support has grown for gastroenterologists to become actively involved in obesity treatment — even to “take ownership” of this field.
In a 2023 article in Gut, Michael Camilleri, MD, AGAF, a gastroenterologist at the Mayo Clinic in Rochester, Minnesota, made the case for the natural fit between gastrointestinal (GI) specialists and obesity management. He noted that obesity is a significant risk factor for GI, pancreatic, and liver diseases. It can even affect inflammatory bowel disease.
“Treating obesity starting when patients present in gastroenterology and hepatology clinics has potential to impact serious consequences of obesity such as cardiovascular risks,” he wrote.
Gastroenterologists already treat GI conditions with pharmacologic and surgical interventions that can also be used to treat obesity and improve glycemic control. These include pancreatic lipase inhibitors and incretin, bariatric endoscopy and surgery, and combination therapies targeting metabolic problems.
This study was supported by the American Heart Association.
Dr. Maruthur reported receiving royalties from a virtual diabetes prevention program. Dr. Pilla reported receiving travel, advisory, and speaker fees from the American Diabetes Association. Numerous authors reported receiving grants from government and nonprofit research funding organizations. Dr. Varady disclosed having no competing interests. Dr. Odda reported receiving research support and honoraria from government nonprofit funding organizations.
A version of this article first appeared on Medscape.com.