Endocrinology

In 2021, diabetes and related complications was the 8th leading cause of death in the United States.¹ As of 2022, more than 11% of the U.S. population had diabetes and 38% of the adult U.S. population had prediabetes.² Diabetes is the most expensive chronic condition in the United States, where $1 of every $4 in health care costs is spent on care.³

Where this is most concerning is diabetes in pregnancy. While childbirth rates in the United States have decreased since the 2007 high of 4.32 million births⁴ to 3.66 million in 2021,⁵ the incidence of diabetes in pregnancy – both pregestational and gestational – has increased. The rate of pregestational diabetes in 2021 was 10.9 per 1,000 births, a 27% increase from 2016 (8.6 per 1,000).⁶ The percentage of those giving birth who also were diagnosed with gestational diabetes mellitus (GDM) was 8.3% in 2021, up from 6.0% in 2016.⁷

Diabetes in pregnancy not only increases risks of adverse events for mother and fetus: Increasing research suggests the condition signals longer-term risks for the mother and child throughout their lifetimes. Adverse outcomes for an infant born to a mother with diabetes include a higher risk of obesity and diabetes as adults, potentially leading to a forward-feeding cycle.

We and our colleagues established the Diabetes in Pregnancy Study Group of North America in 1997 because we had witnessed too frequently the devastating diabetes-induced pregnancy complications in our patients. The mission we set forth was to provide a forum for dialogue among maternal-fetal medicine subspecialists. The three main goals we set forth to support this mission were to provide a catalyst for research, contribute to the creation and refinement of medical policies, and influence professional practices in diabetes in pregnancy.⁸

In the last quarter century, DPSG-NA, through its annual and biennial meetings, has brought together several hundred practitioners that include physicians, nurses, statisticians, researchers, nutritionists, and allied health professionals, among others. As a group, it has improved the detection and management of diabetes in pregnant women and their offspring through knowledge sharing and influencing policies on GDM screening, diagnosis, management, and treatment. Our members have shown that preconceptional counseling for women with diabetes can significantly reduce congenital malformation and perinatal mortality compared with those women with pregestational diabetes who receive no counseling.^9,10

We have addressed a wide variety of topics including the paucity of data in determining the timing of delivery for women with diabetes and the Institute of Medicine/National Academy of Medicine recommendations of gestational weight gain and risks of not adhering to them. We have learned about new scientific discoveries that reveal underlying mechanisms to diabetes-related birth defects and potential therapeutic targets; and we have discussed the health literacy requirements, ethics, and opportunities for lifestyle intervention.^11-16

But we need to do more.

Two risk factors are at play: Women continue to choose to have babies at later ages and their pregnancies continue to be complicated by the rising incidence of obesity (see Figure 1 and Figure 2).

Dr. Reece and Dr. Miodovnik

The global obesity epidemic has become a significant concern for all aspects of health and particularly for diabetes in pregnancy.

Dr. Reece and Dr. Miodovnik

In 1990, 24.9% of women in the United States were obese; in 2010, 35.8%; and now more than 41%. Some experts project that by 2030 more than 80% of women in the United States will be overweight or obese.²¹

If we are to stop this cycle of diabetes begets more diabetes, now more than ever we need to come together and accelerate the research and education around the diabetes in pregnancy. Join us at this year’s DPSG-NA meeting Oct. 26-28 to take part in the knowledge sharing, discussions, and planning. More information can be found online at https://events.dpsg-na.com/home.

Dr. Miodovnik is adjunct professor of obstetrics, gynecology, and reproductive sciences at University of Maryland School of Medicine. Dr. Reece is professor of obstetrics, gynecology, and reproductive sciences and senior scientist at the Center for Birth Defects Research at University of Maryland School of Medicine.

References

1. Xu J et al. Mortality in the United States, 2021. NCHS Data Brief. 2022 Dec;(456):1-8. PMID: 36598387.

2. Centers for Disease Control and Prevention, diabetes data and statistics.

3. American Diabetes Association. The Cost of Diabetes.

4. Martin JA et al. Births: Final data for 2007. Natl Vital Stat Rep. 2010 Aug 9;58(24):1-85. PMID: 21254725.

5. Osterman MJK et al. Births: Final data for 2021. Natl Vital Stat Rep. 2023 Jan;72(1):1-53. PMID: 36723449.

6. Gregory ECW and Ely DM. Trends and characteristics in prepregnancy diabetes: United States, 2016-2021. Natl Vital Stat Rep. 2023 May;72(6):1-13. PMID: 37256333.

7. QuickStats: Percentage of mothers with gestational diabetes, by maternal age – National Vital Statistics System, United States, 2016 and 2021. MMWR Morb Mortal Wkly Rep. 2023 Jan 6;72(1):16. doi: 10.15585/mmwr.mm7201a4.
 

8. Langer O et al. The Diabetes in Pregnancy Study Group of North America – Introduction and summary statement. Prenat Neonat Med. 1998;3(6):514-6.

9. Willhoite MB et al. The impact of preconception counseling on pregnancy outcomes. The experience of the Maine Diabetes in Pregnancy Program. Diabetes Care. 1993 Feb;16(2):450-5. doi: 10.2337/diacare.16.2.450.

10. McElvy SS et al. A focused preconceptional and early pregnancy program in women with type 1 diabetes reduces perinatal mortality and malformation rates to general population levels. J Matern Fetal Med. 2000 Jan-Feb;9(1):14-20. doi: 10.1002/(SICI)1520-6661(200001/02)9:1<14::AID-MFM5>3.0.CO;2-K.

11. Rosen JA et al. The history and contributions of the Diabetes in Pregnancy Study Group of North America (1997-2015). Am J Perinatol. 2016 Nov;33(13):1223-6. doi: 10.1055/s-0036-1585082.

12. Driggers RW and Baschat A. The 12th meeting of the Diabetes in Pregnancy Study Group of North America (DPSG-NA): Introduction and overview. J Matern Fetal Neonatal Med. 2012 Jan;25(1):3-4. doi: 10.3109/14767058.2012.626917.

13. Langer O et al. The proceedings of the Diabetes in Pregnancy Study Group of North America 2009 conference. J Matern Fetal Neonatal Med. 2010 Mar;23(3):196-8. doi: 10.3109/14767050903550634.

14. Reece EA et al. A consensus report of the Diabetes in Pregnancy Study Group of North America Conference, Little Rock, Ark., May 2002. J Matern Fetal Neonatal Med. 2002 Dec;12(6):362-4. doi: 10.1080/jmf.12.6.362.364.

15. Reece EA and Maulik D. A consensus conference of the Diabetes in Pregnancy Study Group of North America. J Matern Fetal Neonatal Med. 2002 Dec;12(6):361. doi: 10.1080/jmf.12.6.361.361.

16. Gabbe SG. Summation of the second meeting of the Diabetes in Pregnancy Study Group of North America (DPSG-NA). J Matern Fetal Med. 2000 Jan-Feb;9(1):3-9.

17. Vital Statistics of the United States 1990: Volume I – Natality.

18. Martin JA et al. Births: final data for 2000. Natl Vital Stat Rep. 2002 Feb 12;50(5):1-101. PMID: 11876093.

19. Martin JA et al. Births: final data for 2010. Natl Vital Stat Rep. 2012 Aug 28;61(1):1-72. PMID: 24974589.

20. CDC Website. Normal weight, overweight, and obesity among adults aged 20 and over, by selected characteristics: United States.

21. Wang Y et al. Has the prevalence of overweight, obesity, and central obesity levelled off in the United States? Trends, patterns, disparities, and future projections for the obesity epidemic. Int J Epidemiol. 2020 Jun 1;49(3):810-23. doi: 10.1093/ije/dyz273.

In 2021, diabetes and related complications was the 8th leading cause of death in the United States.¹ As of 2022, more than 11% of the U.S. population had diabetes and 38% of the adult U.S. population had prediabetes.² Diabetes is the most expensive chronic condition in the United States, where $1 of every $4 in health care costs is spent on care.³

Where this is most concerning is diabetes in pregnancy. While childbirth rates in the United States have decreased since the 2007 high of 4.32 million births⁴ to 3.66 million in 2021,⁵ the incidence of diabetes in pregnancy – both pregestational and gestational – has increased. The rate of pregestational diabetes in 2021 was 10.9 per 1,000 births, a 27% increase from 2016 (8.6 per 1,000).⁶ The percentage of those giving birth who also were diagnosed with gestational diabetes mellitus (GDM) was 8.3% in 2021, up from 6.0% in 2016.⁷

Diabetes in pregnancy not only increases risks of adverse events for mother and fetus: Increasing research suggests the condition signals longer-term risks for the mother and child throughout their lifetimes. Adverse outcomes for an infant born to a mother with diabetes include a higher risk of obesity and diabetes as adults, potentially leading to a forward-feeding cycle.

We and our colleagues established the Diabetes in Pregnancy Study Group of North America in 1997 because we had witnessed too frequently the devastating diabetes-induced pregnancy complications in our patients. The mission we set forth was to provide a forum for dialogue among maternal-fetal medicine subspecialists. The three main goals we set forth to support this mission were to provide a catalyst for research, contribute to the creation and refinement of medical policies, and influence professional practices in diabetes in pregnancy.⁸

In the last quarter century, DPSG-NA, through its annual and biennial meetings, has brought together several hundred practitioners that include physicians, nurses, statisticians, researchers, nutritionists, and allied health professionals, among others. As a group, it has improved the detection and management of diabetes in pregnant women and their offspring through knowledge sharing and influencing policies on GDM screening, diagnosis, management, and treatment. Our members have shown that preconceptional counseling for women with diabetes can significantly reduce congenital malformation and perinatal mortality compared with those women with pregestational diabetes who receive no counseling.^9,10

We have addressed a wide variety of topics including the paucity of data in determining the timing of delivery for women with diabetes and the Institute of Medicine/National Academy of Medicine recommendations of gestational weight gain and risks of not adhering to them. We have learned about new scientific discoveries that reveal underlying mechanisms to diabetes-related birth defects and potential therapeutic targets; and we have discussed the health literacy requirements, ethics, and opportunities for lifestyle intervention.^11-16

But we need to do more.

Two risk factors are at play: Women continue to choose to have babies at later ages and their pregnancies continue to be complicated by the rising incidence of obesity (see Figure 1 and Figure 2).

Dr. Reece and Dr. Miodovnik

The global obesity epidemic has become a significant concern for all aspects of health and particularly for diabetes in pregnancy.

Dr. Reece and Dr. Miodovnik

In 1990, 24.9% of women in the United States were obese; in 2010, 35.8%; and now more than 41%. Some experts project that by 2030 more than 80% of women in the United States will be overweight or obese.²¹

If we are to stop this cycle of diabetes begets more diabetes, now more than ever we need to come together and accelerate the research and education around the diabetes in pregnancy. Join us at this year’s DPSG-NA meeting Oct. 26-28 to take part in the knowledge sharing, discussions, and planning. More information can be found online at https://events.dpsg-na.com/home.

Dr. Miodovnik is adjunct professor of obstetrics, gynecology, and reproductive sciences at University of Maryland School of Medicine. Dr. Reece is professor of obstetrics, gynecology, and reproductive sciences and senior scientist at the Center for Birth Defects Research at University of Maryland School of Medicine.

References

1. Xu J et al. Mortality in the United States, 2021. NCHS Data Brief. 2022 Dec;(456):1-8. PMID: 36598387.

2. Centers for Disease Control and Prevention, diabetes data and statistics.

3. American Diabetes Association. The Cost of Diabetes.

4. Martin JA et al. Births: Final data for 2007. Natl Vital Stat Rep. 2010 Aug 9;58(24):1-85. PMID: 21254725.

5. Osterman MJK et al. Births: Final data for 2021. Natl Vital Stat Rep. 2023 Jan;72(1):1-53. PMID: 36723449.

6. Gregory ECW and Ely DM. Trends and characteristics in prepregnancy diabetes: United States, 2016-2021. Natl Vital Stat Rep. 2023 May;72(6):1-13. PMID: 37256333.

7. QuickStats: Percentage of mothers with gestational diabetes, by maternal age – National Vital Statistics System, United States, 2016 and 2021. MMWR Morb Mortal Wkly Rep. 2023 Jan 6;72(1):16. doi: 10.15585/mmwr.mm7201a4.
 

8. Langer O et al. The Diabetes in Pregnancy Study Group of North America – Introduction and summary statement. Prenat Neonat Med. 1998;3(6):514-6.

9. Willhoite MB et al. The impact of preconception counseling on pregnancy outcomes. The experience of the Maine Diabetes in Pregnancy Program. Diabetes Care. 1993 Feb;16(2):450-5. doi: 10.2337/diacare.16.2.450.

10. McElvy SS et al. A focused preconceptional and early pregnancy program in women with type 1 diabetes reduces perinatal mortality and malformation rates to general population levels. J Matern Fetal Med. 2000 Jan-Feb;9(1):14-20. doi: 10.1002/(SICI)1520-6661(200001/02)9:1<14::AID-MFM5>3.0.CO;2-K.

11. Rosen JA et al. The history and contributions of the Diabetes in Pregnancy Study Group of North America (1997-2015). Am J Perinatol. 2016 Nov;33(13):1223-6. doi: 10.1055/s-0036-1585082.

12. Driggers RW and Baschat A. The 12th meeting of the Diabetes in Pregnancy Study Group of North America (DPSG-NA): Introduction and overview. J Matern Fetal Neonatal Med. 2012 Jan;25(1):3-4. doi: 10.3109/14767058.2012.626917.

13. Langer O et al. The proceedings of the Diabetes in Pregnancy Study Group of North America 2009 conference. J Matern Fetal Neonatal Med. 2010 Mar;23(3):196-8. doi: 10.3109/14767050903550634.

14. Reece EA et al. A consensus report of the Diabetes in Pregnancy Study Group of North America Conference, Little Rock, Ark., May 2002. J Matern Fetal Neonatal Med. 2002 Dec;12(6):362-4. doi: 10.1080/jmf.12.6.362.364.

15. Reece EA and Maulik D. A consensus conference of the Diabetes in Pregnancy Study Group of North America. J Matern Fetal Neonatal Med. 2002 Dec;12(6):361. doi: 10.1080/jmf.12.6.361.361.

16. Gabbe SG. Summation of the second meeting of the Diabetes in Pregnancy Study Group of North America (DPSG-NA). J Matern Fetal Med. 2000 Jan-Feb;9(1):3-9.

17. Vital Statistics of the United States 1990: Volume I – Natality.

18. Martin JA et al. Births: final data for 2000. Natl Vital Stat Rep. 2002 Feb 12;50(5):1-101. PMID: 11876093.

19. Martin JA et al. Births: final data for 2010. Natl Vital Stat Rep. 2012 Aug 28;61(1):1-72. PMID: 24974589.

20. CDC Website. Normal weight, overweight, and obesity among adults aged 20 and over, by selected characteristics: United States.

21. Wang Y et al. Has the prevalence of overweight, obesity, and central obesity levelled off in the United States? Trends, patterns, disparities, and future projections for the obesity epidemic. Int J Epidemiol. 2020 Jun 1;49(3):810-23. doi: 10.1093/ije/dyz273.

In 2021, diabetes and related complications was the 8th leading cause of death in the United States.¹ As of 2022, more than 11% of the U.S. population had diabetes and 38% of the adult U.S. population had prediabetes.² Diabetes is the most expensive chronic condition in the United States, where $1 of every $4 in health care costs is spent on care.³

Where this is most concerning is diabetes in pregnancy. While childbirth rates in the United States have decreased since the 2007 high of 4.32 million births⁴ to 3.66 million in 2021,⁵ the incidence of diabetes in pregnancy – both pregestational and gestational – has increased. The rate of pregestational diabetes in 2021 was 10.9 per 1,000 births, a 27% increase from 2016 (8.6 per 1,000).⁶ The percentage of those giving birth who also were diagnosed with gestational diabetes mellitus (GDM) was 8.3% in 2021, up from 6.0% in 2016.⁷

Diabetes in pregnancy not only increases risks of adverse events for mother and fetus: Increasing research suggests the condition signals longer-term risks for the mother and child throughout their lifetimes. Adverse outcomes for an infant born to a mother with diabetes include a higher risk of obesity and diabetes as adults, potentially leading to a forward-feeding cycle.

We and our colleagues established the Diabetes in Pregnancy Study Group of North America in 1997 because we had witnessed too frequently the devastating diabetes-induced pregnancy complications in our patients. The mission we set forth was to provide a forum for dialogue among maternal-fetal medicine subspecialists. The three main goals we set forth to support this mission were to provide a catalyst for research, contribute to the creation and refinement of medical policies, and influence professional practices in diabetes in pregnancy.⁸

In the last quarter century, DPSG-NA, through its annual and biennial meetings, has brought together several hundred practitioners that include physicians, nurses, statisticians, researchers, nutritionists, and allied health professionals, among others. As a group, it has improved the detection and management of diabetes in pregnant women and their offspring through knowledge sharing and influencing policies on GDM screening, diagnosis, management, and treatment. Our members have shown that preconceptional counseling for women with diabetes can significantly reduce congenital malformation and perinatal mortality compared with those women with pregestational diabetes who receive no counseling.^9,10

We have addressed a wide variety of topics including the paucity of data in determining the timing of delivery for women with diabetes and the Institute of Medicine/National Academy of Medicine recommendations of gestational weight gain and risks of not adhering to them. We have learned about new scientific discoveries that reveal underlying mechanisms to diabetes-related birth defects and potential therapeutic targets; and we have discussed the health literacy requirements, ethics, and opportunities for lifestyle intervention.^11-16

But we need to do more.

Two risk factors are at play: Women continue to choose to have babies at later ages and their pregnancies continue to be complicated by the rising incidence of obesity (see Figure 1 and Figure 2).

Dr. Reece and Dr. Miodovnik

The global obesity epidemic has become a significant concern for all aspects of health and particularly for diabetes in pregnancy.

Dr. Reece and Dr. Miodovnik

In 1990, 24.9% of women in the United States were obese; in 2010, 35.8%; and now more than 41%. Some experts project that by 2030 more than 80% of women in the United States will be overweight or obese.²¹

If we are to stop this cycle of diabetes begets more diabetes, now more than ever we need to come together and accelerate the research and education around the diabetes in pregnancy. Join us at this year’s DPSG-NA meeting Oct. 26-28 to take part in the knowledge sharing, discussions, and planning. More information can be found online at https://events.dpsg-na.com/home.

Dr. Miodovnik is adjunct professor of obstetrics, gynecology, and reproductive sciences at University of Maryland School of Medicine. Dr. Reece is professor of obstetrics, gynecology, and reproductive sciences and senior scientist at the Center for Birth Defects Research at University of Maryland School of Medicine.

References

1. Xu J et al. Mortality in the United States, 2021. NCHS Data Brief. 2022 Dec;(456):1-8. PMID: 36598387.

2. Centers for Disease Control and Prevention, diabetes data and statistics.

3. American Diabetes Association. The Cost of Diabetes.

4. Martin JA et al. Births: Final data for 2007. Natl Vital Stat Rep. 2010 Aug 9;58(24):1-85. PMID: 21254725.

5. Osterman MJK et al. Births: Final data for 2021. Natl Vital Stat Rep. 2023 Jan;72(1):1-53. PMID: 36723449.

6. Gregory ECW and Ely DM. Trends and characteristics in prepregnancy diabetes: United States, 2016-2021. Natl Vital Stat Rep. 2023 May;72(6):1-13. PMID: 37256333.

7. QuickStats: Percentage of mothers with gestational diabetes, by maternal age – National Vital Statistics System, United States, 2016 and 2021. MMWR Morb Mortal Wkly Rep. 2023 Jan 6;72(1):16. doi: 10.15585/mmwr.mm7201a4.
 

8. Langer O et al. The Diabetes in Pregnancy Study Group of North America – Introduction and summary statement. Prenat Neonat Med. 1998;3(6):514-6.

9. Willhoite MB et al. The impact of preconception counseling on pregnancy outcomes. The experience of the Maine Diabetes in Pregnancy Program. Diabetes Care. 1993 Feb;16(2):450-5. doi: 10.2337/diacare.16.2.450.

10. McElvy SS et al. A focused preconceptional and early pregnancy program in women with type 1 diabetes reduces perinatal mortality and malformation rates to general population levels. J Matern Fetal Med. 2000 Jan-Feb;9(1):14-20. doi: 10.1002/(SICI)1520-6661(200001/02)9:1<14::AID-MFM5>3.0.CO;2-K.

11. Rosen JA et al. The history and contributions of the Diabetes in Pregnancy Study Group of North America (1997-2015). Am J Perinatol. 2016 Nov;33(13):1223-6. doi: 10.1055/s-0036-1585082.

12. Driggers RW and Baschat A. The 12th meeting of the Diabetes in Pregnancy Study Group of North America (DPSG-NA): Introduction and overview. J Matern Fetal Neonatal Med. 2012 Jan;25(1):3-4. doi: 10.3109/14767058.2012.626917.

13. Langer O et al. The proceedings of the Diabetes in Pregnancy Study Group of North America 2009 conference. J Matern Fetal Neonatal Med. 2010 Mar;23(3):196-8. doi: 10.3109/14767050903550634.

14. Reece EA et al. A consensus report of the Diabetes in Pregnancy Study Group of North America Conference, Little Rock, Ark., May 2002. J Matern Fetal Neonatal Med. 2002 Dec;12(6):362-4. doi: 10.1080/jmf.12.6.362.364.

15. Reece EA and Maulik D. A consensus conference of the Diabetes in Pregnancy Study Group of North America. J Matern Fetal Neonatal Med. 2002 Dec;12(6):361. doi: 10.1080/jmf.12.6.361.361.

16. Gabbe SG. Summation of the second meeting of the Diabetes in Pregnancy Study Group of North America (DPSG-NA). J Matern Fetal Med. 2000 Jan-Feb;9(1):3-9.

17. Vital Statistics of the United States 1990: Volume I – Natality.

18. Martin JA et al. Births: final data for 2000. Natl Vital Stat Rep. 2002 Feb 12;50(5):1-101. PMID: 11876093.

19. Martin JA et al. Births: final data for 2010. Natl Vital Stat Rep. 2012 Aug 28;61(1):1-72. PMID: 24974589.

20. CDC Website. Normal weight, overweight, and obesity among adults aged 20 and over, by selected characteristics: United States.

21. Wang Y et al. Has the prevalence of overweight, obesity, and central obesity levelled off in the United States? Trends, patterns, disparities, and future projections for the obesity epidemic. Int J Epidemiol. 2020 Jun 1;49(3):810-23. doi: 10.1093/ije/dyz273.

For women who are obese, daily life is wrought with landmines. Whether it’s the challenges of air travel because plane seats are too small, the need to shield themselves from the world’s discriminating eyes, or the great lengths many will go to achieve better health and the promise of longevity, navigating life as an obese person requires a thick skin.

So, it’s no wonder so many are willing to pay more than $1,000 a month out of pocket to get their hands on drugs like semaglutide (Ozempic and Wegovy) or tirzepatide (Mounjaro). The benefits of these drugs, which are part of a new class called glucagonlike peptide–1 (GLP-1) receptor agonists, include significant and rapid weight loss, blood sugar control, and improved life quality; they are unprecedented in a setting where surgery has long been considered the most effective long-term option.

On the flip side, the desire for rapid weight loss and better blood sugar control also comes with an unexpected cost. Many women living with obesity who take oral contraceptives are unaware that these drugs – especially Mounjaro – can interfere with the absorption of birth control pills and how well they work, making an unintended pregnancy more likely.

Neel Shah, MD, an endocrinologist and associate professor at the University of Texas Health Science Center at Houston, said he has had several patients become pregnant without intending to. 

“It was when Mounjaro came out on the market when we started using it,” he said of the drug the Food and Drug Administration approved for type 2 diabetes in 2022. “It [the warning] was in the product insert, but clinically speaking, I don’t know if it was at the top of providers’ minds when they were prescribing Mounjaro.”

When asked if he believed that we were going to be seeing a significant increase in so-called Mounjaro babies, Dr. Shah was sure in his response. 

“Absolutely. We will because the sheer volume [of patients] will increase,” he said.
 

It’s all in the gut

One of the ways that drugs like Mounjaro work is by delaying the time that it takes for food to move from the stomach to the small intestine. Although data are still evolving, it is believed that this process – delayed gastric emptying – may affect the absorption of birth control pills. 

Dr. Shah said another theory is that vomiting, which is a common side effect of these types of drugs, also affects the pills’ ability to prevent pregnancy. 

And “there’s a prolonged period of ramping up the dose because of the GI side effects,” said Pinar Kodaman, MD, PhD, a reproductive endocrinologist and assistant professor of gynecology at Yale University in New Haven, Conn. 

“Initially, at the lowest dose, there may not be a lot of potential effect on absorption and gastric emptying. But as the dose goes up, it becomes more common, and it can cause diarrhea, which is another condition that can affect the absorption of any medication,” she said.
 

Unanticipated outcomes, extra prevention

Roughly 42% of women in the United States are obese, 40% of whom are between the ages of 20 and 39. Although these new drugs can improve fertility outcomes for women who are obese (especially those with polycystic ovary syndrome, or PCOS), only one – Mounjaro – currently carries a warning about birth control pill effectiveness on its label. Unfortunately, it appears that some doctors are unaware or not counseling patients about this risk, and the data are unclear about whether other drugs in this class, like Ozempic and Wegovy, have the same risks. 

“To date, it hasn’t been a typical thing that we counsel about,” said Dr. Kodaman. “It’s all fairly new, but when we have patients on birth control pills, we do review other medications that they are on because some can affect efficacy, and it’s something to keep in mind.”

It’s also unclear if other forms of birth control – for example, birth control patches that deliver through the skin – might carry similar pregnancy risks. Dr. Shah said some of his patients who became pregnant without intending to were using these patches. This raises even more questions, since they deliver drugs through the skin directly into the bloodstream and not through the GI system. 

What can women do to help ensure that they don’t become pregnant while using these drugs? 

“I really think that if patients want to protect themselves from an unplanned pregnancy, that as soon as they start the GLP receptor agonists, it wouldn’t be a bad idea to use condoms, because the onset of action is pretty quick,” said Dr. Kodaman, noting also that “at the lowest dose there may not be a lot of potential effect on gastric emptying. But as the dose goes up, it becomes much more common or can cause diarrhea.” 

Dr. Shah said that in his practice he’s “been telling patients to add barrier contraception” 4 weeks before they start their first dose “and at any dose adjustment.”

Zoobia Chaudhry, an obesity medicine doctor and assistant professor of medicine at Johns Hopkins University in Baltimore, recommends that “patients just make sure that the injection and medication that they take are at least 1 hour apart.”

“Most of the time, patients do take birth control before bedtime, so if the two are spaced, it should be OK,” she said.

Another option is for women to speak to their doctors about other contraceptive options like IUDs or implantable rods, where gastric absorption is not going to be an issue. 

“There’s very little research on this class of drugs,” said Emily Goodstein, a 40-year-old small-business owner in Washington, who recently switched from Ozempic to Mounjaro. “Being a person who lives in a larger body is such a horrifying experience because of the way that the world discriminates against you.”

She appreciates the feeling of being proactive that these new drugs grant. It has “opened up a bunch of opportunities for me to be seen as a full individual by the medical establishment,” she said. “I was willing to take the risk, knowing that I would be on these drugs for the rest of my life.”

In addition to being what Dr. Goodstein refers to as a guinea pig, she said she made sure that her primary care doctor was aware that she was not trying or planning to become pregnant again. (She has a 3-year-old child.) Still, her doctor mentioned only the most common side effects linked to these drugs, like nausea, vomiting, and diarrhea, and did not mention the risk of pregnancy.

“Folks are really not talking about the reproductive implications,” she said, referring to members of a Facebook group on these drugs that she belongs to. 

Like patients themselves, many doctors are just beginning to get their arms around these agents. “Awareness, education, provider involvement, and having a multidisciplinary team could help patients achieve the goals that they set out for themselves,” said Dr. Shah. 

Clear conversations are key.

A version of this article first appeared on WebMD.com.

For women who are obese, daily life is wrought with landmines. Whether it’s the challenges of air travel because plane seats are too small, the need to shield themselves from the world’s discriminating eyes, or the great lengths many will go to achieve better health and the promise of longevity, navigating life as an obese person requires a thick skin.

So, it’s no wonder so many are willing to pay more than $1,000 a month out of pocket to get their hands on drugs like semaglutide (Ozempic and Wegovy) or tirzepatide (Mounjaro). The benefits of these drugs, which are part of a new class called glucagonlike peptide–1 (GLP-1) receptor agonists, include significant and rapid weight loss, blood sugar control, and improved life quality; they are unprecedented in a setting where surgery has long been considered the most effective long-term option.

On the flip side, the desire for rapid weight loss and better blood sugar control also comes with an unexpected cost. Many women living with obesity who take oral contraceptives are unaware that these drugs – especially Mounjaro – can interfere with the absorption of birth control pills and how well they work, making an unintended pregnancy more likely.

Neel Shah, MD, an endocrinologist and associate professor at the University of Texas Health Science Center at Houston, said he has had several patients become pregnant without intending to. 

“It was when Mounjaro came out on the market when we started using it,” he said of the drug the Food and Drug Administration approved for type 2 diabetes in 2022. “It [the warning] was in the product insert, but clinically speaking, I don’t know if it was at the top of providers’ minds when they were prescribing Mounjaro.”

When asked if he believed that we were going to be seeing a significant increase in so-called Mounjaro babies, Dr. Shah was sure in his response. 

“Absolutely. We will because the sheer volume [of patients] will increase,” he said.
 

It’s all in the gut

One of the ways that drugs like Mounjaro work is by delaying the time that it takes for food to move from the stomach to the small intestine. Although data are still evolving, it is believed that this process – delayed gastric emptying – may affect the absorption of birth control pills. 

Dr. Shah said another theory is that vomiting, which is a common side effect of these types of drugs, also affects the pills’ ability to prevent pregnancy. 

And “there’s a prolonged period of ramping up the dose because of the GI side effects,” said Pinar Kodaman, MD, PhD, a reproductive endocrinologist and assistant professor of gynecology at Yale University in New Haven, Conn. 

“Initially, at the lowest dose, there may not be a lot of potential effect on absorption and gastric emptying. But as the dose goes up, it becomes more common, and it can cause diarrhea, which is another condition that can affect the absorption of any medication,” she said.
 

Unanticipated outcomes, extra prevention

Roughly 42% of women in the United States are obese, 40% of whom are between the ages of 20 and 39. Although these new drugs can improve fertility outcomes for women who are obese (especially those with polycystic ovary syndrome, or PCOS), only one – Mounjaro – currently carries a warning about birth control pill effectiveness on its label. Unfortunately, it appears that some doctors are unaware or not counseling patients about this risk, and the data are unclear about whether other drugs in this class, like Ozempic and Wegovy, have the same risks. 

“To date, it hasn’t been a typical thing that we counsel about,” said Dr. Kodaman. “It’s all fairly new, but when we have patients on birth control pills, we do review other medications that they are on because some can affect efficacy, and it’s something to keep in mind.”

It’s also unclear if other forms of birth control – for example, birth control patches that deliver through the skin – might carry similar pregnancy risks. Dr. Shah said some of his patients who became pregnant without intending to were using these patches. This raises even more questions, since they deliver drugs through the skin directly into the bloodstream and not through the GI system. 

What can women do to help ensure that they don’t become pregnant while using these drugs? 

“I really think that if patients want to protect themselves from an unplanned pregnancy, that as soon as they start the GLP receptor agonists, it wouldn’t be a bad idea to use condoms, because the onset of action is pretty quick,” said Dr. Kodaman, noting also that “at the lowest dose there may not be a lot of potential effect on gastric emptying. But as the dose goes up, it becomes much more common or can cause diarrhea.” 

Dr. Shah said that in his practice he’s “been telling patients to add barrier contraception” 4 weeks before they start their first dose “and at any dose adjustment.”

Zoobia Chaudhry, an obesity medicine doctor and assistant professor of medicine at Johns Hopkins University in Baltimore, recommends that “patients just make sure that the injection and medication that they take are at least 1 hour apart.”

“Most of the time, patients do take birth control before bedtime, so if the two are spaced, it should be OK,” she said.

Another option is for women to speak to their doctors about other contraceptive options like IUDs or implantable rods, where gastric absorption is not going to be an issue. 

“There’s very little research on this class of drugs,” said Emily Goodstein, a 40-year-old small-business owner in Washington, who recently switched from Ozempic to Mounjaro. “Being a person who lives in a larger body is such a horrifying experience because of the way that the world discriminates against you.”

She appreciates the feeling of being proactive that these new drugs grant. It has “opened up a bunch of opportunities for me to be seen as a full individual by the medical establishment,” she said. “I was willing to take the risk, knowing that I would be on these drugs for the rest of my life.”

In addition to being what Dr. Goodstein refers to as a guinea pig, she said she made sure that her primary care doctor was aware that she was not trying or planning to become pregnant again. (She has a 3-year-old child.) Still, her doctor mentioned only the most common side effects linked to these drugs, like nausea, vomiting, and diarrhea, and did not mention the risk of pregnancy.

“Folks are really not talking about the reproductive implications,” she said, referring to members of a Facebook group on these drugs that she belongs to. 

Like patients themselves, many doctors are just beginning to get their arms around these agents. “Awareness, education, provider involvement, and having a multidisciplinary team could help patients achieve the goals that they set out for themselves,” said Dr. Shah. 

Clear conversations are key.

A version of this article first appeared on WebMD.com.

For women who are obese, daily life is wrought with landmines. Whether it’s the challenges of air travel because plane seats are too small, the need to shield themselves from the world’s discriminating eyes, or the great lengths many will go to achieve better health and the promise of longevity, navigating life as an obese person requires a thick skin.

So, it’s no wonder so many are willing to pay more than $1,000 a month out of pocket to get their hands on drugs like semaglutide (Ozempic and Wegovy) or tirzepatide (Mounjaro). The benefits of these drugs, which are part of a new class called glucagonlike peptide–1 (GLP-1) receptor agonists, include significant and rapid weight loss, blood sugar control, and improved life quality; they are unprecedented in a setting where surgery has long been considered the most effective long-term option.

On the flip side, the desire for rapid weight loss and better blood sugar control also comes with an unexpected cost. Many women living with obesity who take oral contraceptives are unaware that these drugs – especially Mounjaro – can interfere with the absorption of birth control pills and how well they work, making an unintended pregnancy more likely.

Neel Shah, MD, an endocrinologist and associate professor at the University of Texas Health Science Center at Houston, said he has had several patients become pregnant without intending to. 

“It was when Mounjaro came out on the market when we started using it,” he said of the drug the Food and Drug Administration approved for type 2 diabetes in 2022. “It [the warning] was in the product insert, but clinically speaking, I don’t know if it was at the top of providers’ minds when they were prescribing Mounjaro.”

When asked if he believed that we were going to be seeing a significant increase in so-called Mounjaro babies, Dr. Shah was sure in his response. 

“Absolutely. We will because the sheer volume [of patients] will increase,” he said.
 

It’s all in the gut

One of the ways that drugs like Mounjaro work is by delaying the time that it takes for food to move from the stomach to the small intestine. Although data are still evolving, it is believed that this process – delayed gastric emptying – may affect the absorption of birth control pills. 

Dr. Shah said another theory is that vomiting, which is a common side effect of these types of drugs, also affects the pills’ ability to prevent pregnancy. 

And “there’s a prolonged period of ramping up the dose because of the GI side effects,” said Pinar Kodaman, MD, PhD, a reproductive endocrinologist and assistant professor of gynecology at Yale University in New Haven, Conn. 

“Initially, at the lowest dose, there may not be a lot of potential effect on absorption and gastric emptying. But as the dose goes up, it becomes more common, and it can cause diarrhea, which is another condition that can affect the absorption of any medication,” she said.
 

Unanticipated outcomes, extra prevention

Roughly 42% of women in the United States are obese, 40% of whom are between the ages of 20 and 39. Although these new drugs can improve fertility outcomes for women who are obese (especially those with polycystic ovary syndrome, or PCOS), only one – Mounjaro – currently carries a warning about birth control pill effectiveness on its label. Unfortunately, it appears that some doctors are unaware or not counseling patients about this risk, and the data are unclear about whether other drugs in this class, like Ozempic and Wegovy, have the same risks. 

“To date, it hasn’t been a typical thing that we counsel about,” said Dr. Kodaman. “It’s all fairly new, but when we have patients on birth control pills, we do review other medications that they are on because some can affect efficacy, and it’s something to keep in mind.”

It’s also unclear if other forms of birth control – for example, birth control patches that deliver through the skin – might carry similar pregnancy risks. Dr. Shah said some of his patients who became pregnant without intending to were using these patches. This raises even more questions, since they deliver drugs through the skin directly into the bloodstream and not through the GI system. 

What can women do to help ensure that they don’t become pregnant while using these drugs? 

“I really think that if patients want to protect themselves from an unplanned pregnancy, that as soon as they start the GLP receptor agonists, it wouldn’t be a bad idea to use condoms, because the onset of action is pretty quick,” said Dr. Kodaman, noting also that “at the lowest dose there may not be a lot of potential effect on gastric emptying. But as the dose goes up, it becomes much more common or can cause diarrhea.” 

Dr. Shah said that in his practice he’s “been telling patients to add barrier contraception” 4 weeks before they start their first dose “and at any dose adjustment.”

Zoobia Chaudhry, an obesity medicine doctor and assistant professor of medicine at Johns Hopkins University in Baltimore, recommends that “patients just make sure that the injection and medication that they take are at least 1 hour apart.”

“Most of the time, patients do take birth control before bedtime, so if the two are spaced, it should be OK,” she said.

Another option is for women to speak to their doctors about other contraceptive options like IUDs or implantable rods, where gastric absorption is not going to be an issue. 

“There’s very little research on this class of drugs,” said Emily Goodstein, a 40-year-old small-business owner in Washington, who recently switched from Ozempic to Mounjaro. “Being a person who lives in a larger body is such a horrifying experience because of the way that the world discriminates against you.”

She appreciates the feeling of being proactive that these new drugs grant. It has “opened up a bunch of opportunities for me to be seen as a full individual by the medical establishment,” she said. “I was willing to take the risk, knowing that I would be on these drugs for the rest of my life.”

In addition to being what Dr. Goodstein refers to as a guinea pig, she said she made sure that her primary care doctor was aware that she was not trying or planning to become pregnant again. (She has a 3-year-old child.) Still, her doctor mentioned only the most common side effects linked to these drugs, like nausea, vomiting, and diarrhea, and did not mention the risk of pregnancy.

“Folks are really not talking about the reproductive implications,” she said, referring to members of a Facebook group on these drugs that she belongs to. 

Like patients themselves, many doctors are just beginning to get their arms around these agents. “Awareness, education, provider involvement, and having a multidisciplinary team could help patients achieve the goals that they set out for themselves,” said Dr. Shah. 

Clear conversations are key.

A version of this article first appeared on WebMD.com.

A process your body uses to stay warm in cool weather could one day lead to new therapies for obesity.

Scientists have, for the first time, mapped the precise nerve pathways that activate brown fat, or brown adipose tissue (BAT), a specialized fat that generates heat. Low temperatures kick brown fat into gear, helping the body keep its temperature and burning calories in the process.

“It has long been speculated that activating this type of fat may be useful in treating obesity and related metabolic conditions,” said Preethi Srikanthan, MD, an endocrinologist and professor of medicine who oversaw the research at the UCLA School of Medicine. “The challenge has been finding a way of selectively stimulating [it].”

Brown fat is different from the fat typically linked to obesity: the kind that accumulates around the belly, hips, and thighs. That’s white fat. White fat stores energy; brown fat burns it. That’s because brown fat cells have more mitochondria, a part of the cell that generates energy. 

After dissecting the necks of eight human cadavers, Dr. Srikanthan and her team traced the sympathetic nerve branches in the fat pad above the collarbone – where the largest depot of brown fat in adults is stored. They stained the nerves, took samples, and viewed them under a microscope. 

They found that nerves from brown fat traveled to the third and fourth cranial nerves of the brain, bundles of nerve fibers that control blinking and some eye movements.

In a previous case study, damage to these nerves appeared to block a chemical tracer from reaching brown fat. The evidence suggests that changing this nerve supply could alter brown fat activity, potentially leading to new treatments for obesity and metabolic diseases like type 2 diabetes, Dr. Srikanthan said.
 

A possible mechanism for Ozempic?

Brown fat has already been linked to at least one breakthrough in obesity treatment. Some evidence suggests that popular medications like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro) may affect brown fat activity. These belong to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists. They work by mimicking the hormone GLP-1, which is released in the gut and brain in response to eating glucose (sugary foods or drinks).

“GLP-1 agonists have been shown to increase [brown fat] activity in rodents and humans, but likely indirectly, via activation of specific regions in the brain,” explained Varman Samuel, MD, PhD, an associate professor of medicine at the Yale School of Medicine, New Haven, Conn., and chief of endocrinology for the VA Connecticut Healthcare System. 

The scientific literature is divided on this, but there is enough evidence to support further inquiry, Dr. Srikanthan said. Her team has begun a study to examine that link.
 

Opening the door to future obesity treatments

But their discovery means other new treatments could be on the horizon. 

Previous research had shown that the sympathetic nervous system drives brown fat activity. But now that the UCLA scientists have revealed the exact nerves connecting brown fat to the sympathetic nervous system, we could find ways to stimulate those pathways to activate brown fat – without stimulating the many organs (such as the heart and stomach) also connected to this vast network of nerves, Dr. Srikanthan said. 

Methods for doing that could include medication, electrical stimulation, or heat therapy, according to the study. 

Still, there is reason to temper expectations. “[Brown fat] depots, while highly metabolically active, are quite small,” Dr. Samuel said. “So, the overall contribution to whole-body energy balance in humans will likely be small.”

On the other hand, that prediction doesn’t account for what we don’t know. 

“We’re learning more about how tissues communicate with each other, beyond the release of hormones or metabolites,” Dr. Samuel said. Activating brown fat could trigger “signals that help coordinate whole-body energy metabolism.”

A version of this article first appeared on WebMD.com.

A process your body uses to stay warm in cool weather could one day lead to new therapies for obesity.

Scientists have, for the first time, mapped the precise nerve pathways that activate brown fat, or brown adipose tissue (BAT), a specialized fat that generates heat. Low temperatures kick brown fat into gear, helping the body keep its temperature and burning calories in the process.

“It has long been speculated that activating this type of fat may be useful in treating obesity and related metabolic conditions,” said Preethi Srikanthan, MD, an endocrinologist and professor of medicine who oversaw the research at the UCLA School of Medicine. “The challenge has been finding a way of selectively stimulating [it].”

Brown fat is different from the fat typically linked to obesity: the kind that accumulates around the belly, hips, and thighs. That’s white fat. White fat stores energy; brown fat burns it. That’s because brown fat cells have more mitochondria, a part of the cell that generates energy. 

After dissecting the necks of eight human cadavers, Dr. Srikanthan and her team traced the sympathetic nerve branches in the fat pad above the collarbone – where the largest depot of brown fat in adults is stored. They stained the nerves, took samples, and viewed them under a microscope. 

They found that nerves from brown fat traveled to the third and fourth cranial nerves of the brain, bundles of nerve fibers that control blinking and some eye movements.

In a previous case study, damage to these nerves appeared to block a chemical tracer from reaching brown fat. The evidence suggests that changing this nerve supply could alter brown fat activity, potentially leading to new treatments for obesity and metabolic diseases like type 2 diabetes, Dr. Srikanthan said.
 

A possible mechanism for Ozempic?

Brown fat has already been linked to at least one breakthrough in obesity treatment. Some evidence suggests that popular medications like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro) may affect brown fat activity. These belong to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists. They work by mimicking the hormone GLP-1, which is released in the gut and brain in response to eating glucose (sugary foods or drinks).

“GLP-1 agonists have been shown to increase [brown fat] activity in rodents and humans, but likely indirectly, via activation of specific regions in the brain,” explained Varman Samuel, MD, PhD, an associate professor of medicine at the Yale School of Medicine, New Haven, Conn., and chief of endocrinology for the VA Connecticut Healthcare System. 

The scientific literature is divided on this, but there is enough evidence to support further inquiry, Dr. Srikanthan said. Her team has begun a study to examine that link.
 

Opening the door to future obesity treatments

But their discovery means other new treatments could be on the horizon. 

Previous research had shown that the sympathetic nervous system drives brown fat activity. But now that the UCLA scientists have revealed the exact nerves connecting brown fat to the sympathetic nervous system, we could find ways to stimulate those pathways to activate brown fat – without stimulating the many organs (such as the heart and stomach) also connected to this vast network of nerves, Dr. Srikanthan said. 

Methods for doing that could include medication, electrical stimulation, or heat therapy, according to the study. 

Still, there is reason to temper expectations. “[Brown fat] depots, while highly metabolically active, are quite small,” Dr. Samuel said. “So, the overall contribution to whole-body energy balance in humans will likely be small.”

On the other hand, that prediction doesn’t account for what we don’t know. 

“We’re learning more about how tissues communicate with each other, beyond the release of hormones or metabolites,” Dr. Samuel said. Activating brown fat could trigger “signals that help coordinate whole-body energy metabolism.”

A version of this article first appeared on WebMD.com.

A process your body uses to stay warm in cool weather could one day lead to new therapies for obesity.

Scientists have, for the first time, mapped the precise nerve pathways that activate brown fat, or brown adipose tissue (BAT), a specialized fat that generates heat. Low temperatures kick brown fat into gear, helping the body keep its temperature and burning calories in the process.

“It has long been speculated that activating this type of fat may be useful in treating obesity and related metabolic conditions,” said Preethi Srikanthan, MD, an endocrinologist and professor of medicine who oversaw the research at the UCLA School of Medicine. “The challenge has been finding a way of selectively stimulating [it].”

Brown fat is different from the fat typically linked to obesity: the kind that accumulates around the belly, hips, and thighs. That’s white fat. White fat stores energy; brown fat burns it. That’s because brown fat cells have more mitochondria, a part of the cell that generates energy. 

After dissecting the necks of eight human cadavers, Dr. Srikanthan and her team traced the sympathetic nerve branches in the fat pad above the collarbone – where the largest depot of brown fat in adults is stored. They stained the nerves, took samples, and viewed them under a microscope. 

They found that nerves from brown fat traveled to the third and fourth cranial nerves of the brain, bundles of nerve fibers that control blinking and some eye movements.

In a previous case study, damage to these nerves appeared to block a chemical tracer from reaching brown fat. The evidence suggests that changing this nerve supply could alter brown fat activity, potentially leading to new treatments for obesity and metabolic diseases like type 2 diabetes, Dr. Srikanthan said.
 

A possible mechanism for Ozempic?

Brown fat has already been linked to at least one breakthrough in obesity treatment. Some evidence suggests that popular medications like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro) may affect brown fat activity. These belong to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists. They work by mimicking the hormone GLP-1, which is released in the gut and brain in response to eating glucose (sugary foods or drinks).

“GLP-1 agonists have been shown to increase [brown fat] activity in rodents and humans, but likely indirectly, via activation of specific regions in the brain,” explained Varman Samuel, MD, PhD, an associate professor of medicine at the Yale School of Medicine, New Haven, Conn., and chief of endocrinology for the VA Connecticut Healthcare System. 

The scientific literature is divided on this, but there is enough evidence to support further inquiry, Dr. Srikanthan said. Her team has begun a study to examine that link.
 

Opening the door to future obesity treatments

But their discovery means other new treatments could be on the horizon. 

Previous research had shown that the sympathetic nervous system drives brown fat activity. But now that the UCLA scientists have revealed the exact nerves connecting brown fat to the sympathetic nervous system, we could find ways to stimulate those pathways to activate brown fat – without stimulating the many organs (such as the heart and stomach) also connected to this vast network of nerves, Dr. Srikanthan said. 

Methods for doing that could include medication, electrical stimulation, or heat therapy, according to the study. 

Still, there is reason to temper expectations. “[Brown fat] depots, while highly metabolically active, are quite small,” Dr. Samuel said. “So, the overall contribution to whole-body energy balance in humans will likely be small.”

On the other hand, that prediction doesn’t account for what we don’t know. 

“We’re learning more about how tissues communicate with each other, beyond the release of hormones or metabolites,” Dr. Samuel said. Activating brown fat could trigger “signals that help coordinate whole-body energy metabolism.”

A version of this article first appeared on WebMD.com.

VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.

The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.

As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.

“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.

Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.

The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.

Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m². Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.

The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).

The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.

Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.

Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”

Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.

The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.

As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.

“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.

Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.

The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.

Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m². Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.

The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).

The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.

Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.

Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”

Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.

The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.

As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.

“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.

Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.

The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.

Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m². Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.

The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).

The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.

Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.

Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”

Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VANCOUVER – A highly controlled retrospective analysis suggests that denosumab (Prolia) leads to greater reduction in fracture risk than does zoledronic acid (Reclast) among treatment-naive postmenopausal women with osteoporosis.

A previous head-to-head comparison showed that denosumab increased bone mineral density at key skeletal sites compared with zoledronic acid, but only a single, small observational study has examined fracture risk, and it found no difference.

The new study, presented at the annual meeting of the American Society for Bone and Mineral Research, used a relatively new method of real-world comparative effectiveness analysis called negative control outcome (NCO) to analyze Medicare fee-for-service data.

NCO analysis takes extra pains to remove bias through data that might be linked to potential confounders but could not reasonably be attributed to a drug. For example, people who have greater contact with the health care system may be more likely to get one drug or another. The researchers used the frequency of receiving a flu or pneumonia vaccine as a proxy for this. If the two comparison groups had a significant difference in a proxy, it suggested a hidden bias and forced the researchers to abandon those groupings. Another example used car accidents as a proxy for cognitive impairment.

“If you find meaningful differences between the two groups, and you can say there’s no way a bone drug could account for these differences, then we shouldn’t do this analysis because these groups just aren’t comparable. They probably differ by that confounding factor we couldn’t measure,” said Jeffrey Curtis, MD, who presented the study. He is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

The study strongly suggests superiority for denosumab. “There was a significant difference in multiple different groupings of fractures – beginning at year 2, extending to year 3 and even out to year 5 – that showed that there is a significant reduction in fracture risk if you get treated with denosumab [that was greater] than if you get treated with zoledronic acid,” Dr. Curtis said.

The researchers weighed 118 covariates and ultimately identified a population of 90,805 women taking denosumab and 37,328 taking zoledronic acid that was equally balanced in all patient characteristics. The mean age was about 75 years in the denosumab group and 74 in the zoledronic acid group.

The researchers found a 34% lower risk for hip fracture in the denosumab group by 5 years (relative risk, 0.66; 95% confidence interval, 0.43-0.90).

Similar patterns in fracture risk reduction were observed at 5 years for nonvertebral fracture (RR, 0.67; 95% CI, 0.52-0.82), nonhip nonvertebral fracture (RR, 0.69; 95% CI, 0.50-0.88), and major osteoporotic fracture (RR, 0.74; 95% CI, 0.59-0.89).

During the Q&A session after the talk, one audience member commented that the study was limited because the researchers only followed patients who received zoledronic acid for 60 days, which could have missed potential long-term benefits of the drug, especially since bisphosphonates have a lengthy skeletal retention time. Dr. Curtis acknowledged the point but said, “Usually, that’s not something we do, but these are different enough mechanisms of action that it may be warranted at least as a sensitivity analysis,” he said.

The study and its methodology were impressive, according to Yumie Rhee, MD, who comoderated the session where the study was presented. “I think they did a really good job by doing the negative control analysis. We’re not going to have a head-to-head clinical trial, so we don’t know the real fracture reduction differences [between denosumab and zoledronic acid]. [The NCO analysis] is more than the propensity matching score that we do usually,” said Dr. Rhee, who is a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea.

In particular, the study showed a significantly greater reduction in hip fractures with denosumab. “Even in the RCTs, it was really hard to see the reduction in hip fracture, so I think this is showing much stronger data for denosumab. Especially in patients who have more [general fracture] risk and patients with higher hip fracture risk, I would go with denosumab,” Dr. Rhee said.

Her comoderator, Maria Zanchetta, MD, agreed. “It can have clinical implication, because we think denosumab is better than [zoledronic acid] for higher-risk patients, but we didn’t have the evidence. So at least we have a new [study] to look at, and I think it’s very important for our practice,” said Dr. Zanchetta, who is a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires.

The study was funded by Amgen, which markets denosumab. Dr. Curtis has consulted for Amgen. Dr. Rhee and Dr. Zanchetta report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VANCOUVER – A highly controlled retrospective analysis suggests that denosumab (Prolia) leads to greater reduction in fracture risk than does zoledronic acid (Reclast) among treatment-naive postmenopausal women with osteoporosis.

A previous head-to-head comparison showed that denosumab increased bone mineral density at key skeletal sites compared with zoledronic acid, but only a single, small observational study has examined fracture risk, and it found no difference.

The new study, presented at the annual meeting of the American Society for Bone and Mineral Research, used a relatively new method of real-world comparative effectiveness analysis called negative control outcome (NCO) to analyze Medicare fee-for-service data.

NCO analysis takes extra pains to remove bias through data that might be linked to potential confounders but could not reasonably be attributed to a drug. For example, people who have greater contact with the health care system may be more likely to get one drug or another. The researchers used the frequency of receiving a flu or pneumonia vaccine as a proxy for this. If the two comparison groups had a significant difference in a proxy, it suggested a hidden bias and forced the researchers to abandon those groupings. Another example used car accidents as a proxy for cognitive impairment.

“If you find meaningful differences between the two groups, and you can say there’s no way a bone drug could account for these differences, then we shouldn’t do this analysis because these groups just aren’t comparable. They probably differ by that confounding factor we couldn’t measure,” said Jeffrey Curtis, MD, who presented the study. He is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

The study strongly suggests superiority for denosumab. “There was a significant difference in multiple different groupings of fractures – beginning at year 2, extending to year 3 and even out to year 5 – that showed that there is a significant reduction in fracture risk if you get treated with denosumab [that was greater] than if you get treated with zoledronic acid,” Dr. Curtis said.

The researchers weighed 118 covariates and ultimately identified a population of 90,805 women taking denosumab and 37,328 taking zoledronic acid that was equally balanced in all patient characteristics. The mean age was about 75 years in the denosumab group and 74 in the zoledronic acid group.

The researchers found a 34% lower risk for hip fracture in the denosumab group by 5 years (relative risk, 0.66; 95% confidence interval, 0.43-0.90).

Similar patterns in fracture risk reduction were observed at 5 years for nonvertebral fracture (RR, 0.67; 95% CI, 0.52-0.82), nonhip nonvertebral fracture (RR, 0.69; 95% CI, 0.50-0.88), and major osteoporotic fracture (RR, 0.74; 95% CI, 0.59-0.89).

During the Q&A session after the talk, one audience member commented that the study was limited because the researchers only followed patients who received zoledronic acid for 60 days, which could have missed potential long-term benefits of the drug, especially since bisphosphonates have a lengthy skeletal retention time. Dr. Curtis acknowledged the point but said, “Usually, that’s not something we do, but these are different enough mechanisms of action that it may be warranted at least as a sensitivity analysis,” he said.

The study and its methodology were impressive, according to Yumie Rhee, MD, who comoderated the session where the study was presented. “I think they did a really good job by doing the negative control analysis. We’re not going to have a head-to-head clinical trial, so we don’t know the real fracture reduction differences [between denosumab and zoledronic acid]. [The NCO analysis] is more than the propensity matching score that we do usually,” said Dr. Rhee, who is a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea.

In particular, the study showed a significantly greater reduction in hip fractures with denosumab. “Even in the RCTs, it was really hard to see the reduction in hip fracture, so I think this is showing much stronger data for denosumab. Especially in patients who have more [general fracture] risk and patients with higher hip fracture risk, I would go with denosumab,” Dr. Rhee said.

Her comoderator, Maria Zanchetta, MD, agreed. “It can have clinical implication, because we think denosumab is better than [zoledronic acid] for higher-risk patients, but we didn’t have the evidence. So at least we have a new [study] to look at, and I think it’s very important for our practice,” said Dr. Zanchetta, who is a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires.

The study was funded by Amgen, which markets denosumab. Dr. Curtis has consulted for Amgen. Dr. Rhee and Dr. Zanchetta report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VANCOUVER – A highly controlled retrospective analysis suggests that denosumab (Prolia) leads to greater reduction in fracture risk than does zoledronic acid (Reclast) among treatment-naive postmenopausal women with osteoporosis.

A previous head-to-head comparison showed that denosumab increased bone mineral density at key skeletal sites compared with zoledronic acid, but only a single, small observational study has examined fracture risk, and it found no difference.

The new study, presented at the annual meeting of the American Society for Bone and Mineral Research, used a relatively new method of real-world comparative effectiveness analysis called negative control outcome (NCO) to analyze Medicare fee-for-service data.

NCO analysis takes extra pains to remove bias through data that might be linked to potential confounders but could not reasonably be attributed to a drug. For example, people who have greater contact with the health care system may be more likely to get one drug or another. The researchers used the frequency of receiving a flu or pneumonia vaccine as a proxy for this. If the two comparison groups had a significant difference in a proxy, it suggested a hidden bias and forced the researchers to abandon those groupings. Another example used car accidents as a proxy for cognitive impairment.

“If you find meaningful differences between the two groups, and you can say there’s no way a bone drug could account for these differences, then we shouldn’t do this analysis because these groups just aren’t comparable. They probably differ by that confounding factor we couldn’t measure,” said Jeffrey Curtis, MD, who presented the study. He is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

The study strongly suggests superiority for denosumab. “There was a significant difference in multiple different groupings of fractures – beginning at year 2, extending to year 3 and even out to year 5 – that showed that there is a significant reduction in fracture risk if you get treated with denosumab [that was greater] than if you get treated with zoledronic acid,” Dr. Curtis said.

The researchers weighed 118 covariates and ultimately identified a population of 90,805 women taking denosumab and 37,328 taking zoledronic acid that was equally balanced in all patient characteristics. The mean age was about 75 years in the denosumab group and 74 in the zoledronic acid group.

The researchers found a 34% lower risk for hip fracture in the denosumab group by 5 years (relative risk, 0.66; 95% confidence interval, 0.43-0.90).

Similar patterns in fracture risk reduction were observed at 5 years for nonvertebral fracture (RR, 0.67; 95% CI, 0.52-0.82), nonhip nonvertebral fracture (RR, 0.69; 95% CI, 0.50-0.88), and major osteoporotic fracture (RR, 0.74; 95% CI, 0.59-0.89).

During the Q&A session after the talk, one audience member commented that the study was limited because the researchers only followed patients who received zoledronic acid for 60 days, which could have missed potential long-term benefits of the drug, especially since bisphosphonates have a lengthy skeletal retention time. Dr. Curtis acknowledged the point but said, “Usually, that’s not something we do, but these are different enough mechanisms of action that it may be warranted at least as a sensitivity analysis,” he said.

The study and its methodology were impressive, according to Yumie Rhee, MD, who comoderated the session where the study was presented. “I think they did a really good job by doing the negative control analysis. We’re not going to have a head-to-head clinical trial, so we don’t know the real fracture reduction differences [between denosumab and zoledronic acid]. [The NCO analysis] is more than the propensity matching score that we do usually,” said Dr. Rhee, who is a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea.

In particular, the study showed a significantly greater reduction in hip fractures with denosumab. “Even in the RCTs, it was really hard to see the reduction in hip fracture, so I think this is showing much stronger data for denosumab. Especially in patients who have more [general fracture] risk and patients with higher hip fracture risk, I would go with denosumab,” Dr. Rhee said.

Her comoderator, Maria Zanchetta, MD, agreed. “It can have clinical implication, because we think denosumab is better than [zoledronic acid] for higher-risk patients, but we didn’t have the evidence. So at least we have a new [study] to look at, and I think it’s very important for our practice,” said Dr. Zanchetta, who is a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires.

The study was funded by Amgen, which markets denosumab. Dr. Curtis has consulted for Amgen. Dr. Rhee and Dr. Zanchetta report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Treatment of vasomotor symptoms with estetrol (E4) led to improvements in postmenopausal patients’ lipid profiles and blood glucose, according to findings of a phase 3 clinical trial presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

Participants taking estetrol experienced a decrease in hemoglobin A1c, fasting plasma glucose, total cholesterol, LDL and lipoprotein as well as an increase in HDL cholesterol, according to the findings presented by Wolf Utian, MD, PhD, DSC, a professor emeritus of reproductive biology at Case Western Reserve University, Cleveland, and medical director emeritus of the Menopause Society.

A separate poster at the conference from the same trial also reported significant improvements from estetrol in quality of life, including that related to vasomotor symptoms, and several psychosocial and sexual functioning areas.

Mayo Clinic

E4 is already available as combination oral contraception and is now being considered for treating vasomotor symptoms, explained Chrisandra Shufelt, MD, professor and chair of general internal of medicine and associate director of the Women’s Health Research Center at Mayo Clinic Florida, who was not involved in the study.
 

Background on estetrol

E4 is a human fetal liver estrogen produced during pregnancy that’s synthesized from plants for pharmaceutical use, including as the oral contraceptive drospirenone, Dr. Utian told attendees. It’s classified as a native estrogen with selective tissue activity (NEST), he said.

“E4 is a completely different native estrogen with oral administration mimicking the benefits of transdermals and hence safe and effective,” Dr. Utian said in an interview. “It would be a significant new addition to the pharmaceutical armamentarium.”

Two phase 3 trials presented by Dr. Utian at the same conference last year found estetrol reduced the frequency and severity of moderate to severe vasomotor symptoms, and a previous phase 2 trial finding vasomotor and genitourinary symptom benefits suggested it had potential benefits for lipids, carbohydrate metabolism, and bone turnover.

“In summary, E4 at a daily dose of 15 mg exhibited estrogenic effects in the vagina, leading to improved vaginal health and reduced signs of atrophy, emerging as a promising treatment option not only for vasomotor symptoms but also for other significant menopausal symptoms,” Dr. Utian said. “E4 could offer comprehensive relief for women experiencing a range of menopause-related discomforts.”

Dr. Utian also referenced a 2017 trial in which estetrol positively impacted lipid profiles, “lowering low-density lipoprotein cholesterol, increasing high-density lipoprotein cholesterol, and showing minimal influence on triglycerides,” he said. “Importantly, estetrol was associated with a significant decrease in osteocalcin levels in the higher dose groups, suggesting a potential preventive effect on bone loss,” he added. A recent review of the overall evidence on estetrol suggests its use is “promising,” Dr. Utian noted.
 

Current trial

His current randomized controlled phase 3 trial included postmenopausal women ages 40-65 from 151 sites in 14 countries in Europe, Latin America, and North America, and Russia. Among the 640 participants in the trial, 213 women randomly received 15 mg of estetrol, 213 women received 20 mg of estetrol, and 214 women received a placebo every day for 3 months. All women without hysterectomies also received 200 mg of progesterone once daily for two weeks after completing the estetrol treatment to protect the endometrium.

Researchers took blood samples from the participants at baseline and week 12 to assess total cholesterol, LDL, HDL, the total cholesterol/HDL ratio, triglycerides, lipoprotein A, fasting plasma glucose, insulin, and A1c.

Compared with women in the placebo group, women in both the 15 mg and 20 mg groups saw a statistically significant decrease in lipoprotein A and in the ratio of total cholesterol to HDL, and a statistically significant increase in HDL. Only the women in the 15 mg group saw a statistically significant decrease in LDL and increase in triglycerides; an increase in triglycerides in the 20 mg group did not reach statistical significance.

Statistically significant decreases in fasting plasma glucose and A1c also occurred in both treatment groups, but a decrease in insulin levels and in the homeostasis model-assessment-estimated insulin resistance (HOMA-IR) seen in both treatment arms did not reach significance.

“While the mean changes after 12 weeks from baseline overall were small changes to the cholesterol and blood sugar profiles, they are clinically meaningful because it suggests that E4 does not have any adverse effects to these measures,” Dr. Shufelt said in an interview. “An advantage is that this gives us another hormone option for vasomotor symptoms since it is a native estrogen with selective tissue.”

It’s too early, however, to determine whether estetrol offers benefits in terms of its safety profile, compared with currently available therapies, Dr. Shufelt said.

”These findings of E4 are similar to how oral estradiol changes lipids, which finds an increase in high-density lipoprotein cholesterol, and decreases plasma concentrations of total and low-density lipoprotein cholesterol. an increase in HDL-C and triglycerides and decrease in LDL-C,” she said.
 

Poster findings also promising

For the findings reported in the poster, researchers assessed quality of life and the clinical meaningfulness of vasomotor symptoms’ reduction at baseline and 12 weeks using the Menopause-Specific Quality of Life (MENQOL) questionnaire and the Clinical Global Impression questionnaire, respectively. They also assessed women’s self-reported genitourinary symptoms, including vaginal dryness, pain during urination, vaginal pain and bleeding related to sex, and vaginal or vulvar irritation or itching. Most of these findings primarily confirmed previous positive effects from E4 in other trials.

Women in both the 15 mg and 20 mg estetrol groups reported a statistically significant improvement at 12 weeks, compared with placebo, in their total MENQOL score and in the vasomotor, psychosocial, and sexual functioning domain scores (P < .05). Those in the 20 mg group also had a statistically significant improvement in their physical domain score (P < .05).

Although numerical improvements in genitourinary symptoms occurred at 12 weeks across all three groups, the only statistically significant difference from baseline occurred in patients taking 15 mg of estetrol, who experienced a decrease in vaginal dryness and vaginal pain during sex (P = .0142 and P = .003, respectively).

The Clinical Global Impression questionnaire asked women at 4 and 12 weeks to rate on a seven-item Likert scale their response to this question: “Rate the total improvement, whether or not in your judgment it is due entirely to drug treatment. Compared to your condition at admission to the study, how much has it changed?” Responses of “very much improved” and “much improved” counted as a clinically meaningful difference.

Compared with 27.9% of patients in the placebo group, 52.9% of patients in the 15 mg group and 59.8% of patients in the 20 mg group rated the weekly frequency of moderate to severe vasomotor symptoms as “much improved” or “very much improved” at 4 weeks (P < .0001). At 12 weeks, those numbers rose to 47% in the placebo group, 73.3% in the 15 mg group and 77.8% in the 20 mg group (P < .0001).

The trial’s primary limitation at this point is having only a 12-week follow-up, Dr. Shufelt said, though a few other questions remain.

“Because the two phase 3 RCTs included hysterectomized and nonhysterectomized women, it was unclear how many women in the study had E4 alone versus E4 with progesterone, as that might play a role in both cholesterol and carbohydrate metabolism,” Dr. Shufelt said. “While baseline data was not presented, it would also be important to know baseline values for the women and confirm that none were on lipid-lowering medications.”

The research was funded by Estetra SRL, an affiliate of Mithra Pharmaceuticals. Dr. Utian is a member of the Mithra and Elektra Scientific Advisory Boards. Dr. Shufelt has no disclosures.
 

PHILADELPHIA – Treatment of vasomotor symptoms with estetrol (E4) led to improvements in postmenopausal patients’ lipid profiles and blood glucose, according to findings of a phase 3 clinical trial presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

Participants taking estetrol experienced a decrease in hemoglobin A1c, fasting plasma glucose, total cholesterol, LDL and lipoprotein as well as an increase in HDL cholesterol, according to the findings presented by Wolf Utian, MD, PhD, DSC, a professor emeritus of reproductive biology at Case Western Reserve University, Cleveland, and medical director emeritus of the Menopause Society.

A separate poster at the conference from the same trial also reported significant improvements from estetrol in quality of life, including that related to vasomotor symptoms, and several psychosocial and sexual functioning areas.

Mayo Clinic

E4 is already available as combination oral contraception and is now being considered for treating vasomotor symptoms, explained Chrisandra Shufelt, MD, professor and chair of general internal of medicine and associate director of the Women’s Health Research Center at Mayo Clinic Florida, who was not involved in the study.
 

Background on estetrol

E4 is a human fetal liver estrogen produced during pregnancy that’s synthesized from plants for pharmaceutical use, including as the oral contraceptive drospirenone, Dr. Utian told attendees. It’s classified as a native estrogen with selective tissue activity (NEST), he said.

“E4 is a completely different native estrogen with oral administration mimicking the benefits of transdermals and hence safe and effective,” Dr. Utian said in an interview. “It would be a significant new addition to the pharmaceutical armamentarium.”

Two phase 3 trials presented by Dr. Utian at the same conference last year found estetrol reduced the frequency and severity of moderate to severe vasomotor symptoms, and a previous phase 2 trial finding vasomotor and genitourinary symptom benefits suggested it had potential benefits for lipids, carbohydrate metabolism, and bone turnover.

“In summary, E4 at a daily dose of 15 mg exhibited estrogenic effects in the vagina, leading to improved vaginal health and reduced signs of atrophy, emerging as a promising treatment option not only for vasomotor symptoms but also for other significant menopausal symptoms,” Dr. Utian said. “E4 could offer comprehensive relief for women experiencing a range of menopause-related discomforts.”

Dr. Utian also referenced a 2017 trial in which estetrol positively impacted lipid profiles, “lowering low-density lipoprotein cholesterol, increasing high-density lipoprotein cholesterol, and showing minimal influence on triglycerides,” he said. “Importantly, estetrol was associated with a significant decrease in osteocalcin levels in the higher dose groups, suggesting a potential preventive effect on bone loss,” he added. A recent review of the overall evidence on estetrol suggests its use is “promising,” Dr. Utian noted.
 

Current trial

His current randomized controlled phase 3 trial included postmenopausal women ages 40-65 from 151 sites in 14 countries in Europe, Latin America, and North America, and Russia. Among the 640 participants in the trial, 213 women randomly received 15 mg of estetrol, 213 women received 20 mg of estetrol, and 214 women received a placebo every day for 3 months. All women without hysterectomies also received 200 mg of progesterone once daily for two weeks after completing the estetrol treatment to protect the endometrium.

Researchers took blood samples from the participants at baseline and week 12 to assess total cholesterol, LDL, HDL, the total cholesterol/HDL ratio, triglycerides, lipoprotein A, fasting plasma glucose, insulin, and A1c.

Compared with women in the placebo group, women in both the 15 mg and 20 mg groups saw a statistically significant decrease in lipoprotein A and in the ratio of total cholesterol to HDL, and a statistically significant increase in HDL. Only the women in the 15 mg group saw a statistically significant decrease in LDL and increase in triglycerides; an increase in triglycerides in the 20 mg group did not reach statistical significance.

Statistically significant decreases in fasting plasma glucose and A1c also occurred in both treatment groups, but a decrease in insulin levels and in the homeostasis model-assessment-estimated insulin resistance (HOMA-IR) seen in both treatment arms did not reach significance.

“While the mean changes after 12 weeks from baseline overall were small changes to the cholesterol and blood sugar profiles, they are clinically meaningful because it suggests that E4 does not have any adverse effects to these measures,” Dr. Shufelt said in an interview. “An advantage is that this gives us another hormone option for vasomotor symptoms since it is a native estrogen with selective tissue.”

It’s too early, however, to determine whether estetrol offers benefits in terms of its safety profile, compared with currently available therapies, Dr. Shufelt said.

”These findings of E4 are similar to how oral estradiol changes lipids, which finds an increase in high-density lipoprotein cholesterol, and decreases plasma concentrations of total and low-density lipoprotein cholesterol. an increase in HDL-C and triglycerides and decrease in LDL-C,” she said.
 

Poster findings also promising

For the findings reported in the poster, researchers assessed quality of life and the clinical meaningfulness of vasomotor symptoms’ reduction at baseline and 12 weeks using the Menopause-Specific Quality of Life (MENQOL) questionnaire and the Clinical Global Impression questionnaire, respectively. They also assessed women’s self-reported genitourinary symptoms, including vaginal dryness, pain during urination, vaginal pain and bleeding related to sex, and vaginal or vulvar irritation or itching. Most of these findings primarily confirmed previous positive effects from E4 in other trials.

Women in both the 15 mg and 20 mg estetrol groups reported a statistically significant improvement at 12 weeks, compared with placebo, in their total MENQOL score and in the vasomotor, psychosocial, and sexual functioning domain scores (P < .05). Those in the 20 mg group also had a statistically significant improvement in their physical domain score (P < .05).

Although numerical improvements in genitourinary symptoms occurred at 12 weeks across all three groups, the only statistically significant difference from baseline occurred in patients taking 15 mg of estetrol, who experienced a decrease in vaginal dryness and vaginal pain during sex (P = .0142 and P = .003, respectively).

The Clinical Global Impression questionnaire asked women at 4 and 12 weeks to rate on a seven-item Likert scale their response to this question: “Rate the total improvement, whether or not in your judgment it is due entirely to drug treatment. Compared to your condition at admission to the study, how much has it changed?” Responses of “very much improved” and “much improved” counted as a clinically meaningful difference.

Compared with 27.9% of patients in the placebo group, 52.9% of patients in the 15 mg group and 59.8% of patients in the 20 mg group rated the weekly frequency of moderate to severe vasomotor symptoms as “much improved” or “very much improved” at 4 weeks (P < .0001). At 12 weeks, those numbers rose to 47% in the placebo group, 73.3% in the 15 mg group and 77.8% in the 20 mg group (P < .0001).

The trial’s primary limitation at this point is having only a 12-week follow-up, Dr. Shufelt said, though a few other questions remain.

“Because the two phase 3 RCTs included hysterectomized and nonhysterectomized women, it was unclear how many women in the study had E4 alone versus E4 with progesterone, as that might play a role in both cholesterol and carbohydrate metabolism,” Dr. Shufelt said. “While baseline data was not presented, it would also be important to know baseline values for the women and confirm that none were on lipid-lowering medications.”

The research was funded by Estetra SRL, an affiliate of Mithra Pharmaceuticals. Dr. Utian is a member of the Mithra and Elektra Scientific Advisory Boards. Dr. Shufelt has no disclosures.
 

PHILADELPHIA – Treatment of vasomotor symptoms with estetrol (E4) led to improvements in postmenopausal patients’ lipid profiles and blood glucose, according to findings of a phase 3 clinical trial presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

Participants taking estetrol experienced a decrease in hemoglobin A1c, fasting plasma glucose, total cholesterol, LDL and lipoprotein as well as an increase in HDL cholesterol, according to the findings presented by Wolf Utian, MD, PhD, DSC, a professor emeritus of reproductive biology at Case Western Reserve University, Cleveland, and medical director emeritus of the Menopause Society.

A separate poster at the conference from the same trial also reported significant improvements from estetrol in quality of life, including that related to vasomotor symptoms, and several psychosocial and sexual functioning areas.

Mayo Clinic

E4 is already available as combination oral contraception and is now being considered for treating vasomotor symptoms, explained Chrisandra Shufelt, MD, professor and chair of general internal of medicine and associate director of the Women’s Health Research Center at Mayo Clinic Florida, who was not involved in the study.
 

Background on estetrol

E4 is a human fetal liver estrogen produced during pregnancy that’s synthesized from plants for pharmaceutical use, including as the oral contraceptive drospirenone, Dr. Utian told attendees. It’s classified as a native estrogen with selective tissue activity (NEST), he said.

“E4 is a completely different native estrogen with oral administration mimicking the benefits of transdermals and hence safe and effective,” Dr. Utian said in an interview. “It would be a significant new addition to the pharmaceutical armamentarium.”

Two phase 3 trials presented by Dr. Utian at the same conference last year found estetrol reduced the frequency and severity of moderate to severe vasomotor symptoms, and a previous phase 2 trial finding vasomotor and genitourinary symptom benefits suggested it had potential benefits for lipids, carbohydrate metabolism, and bone turnover.

“In summary, E4 at a daily dose of 15 mg exhibited estrogenic effects in the vagina, leading to improved vaginal health and reduced signs of atrophy, emerging as a promising treatment option not only for vasomotor symptoms but also for other significant menopausal symptoms,” Dr. Utian said. “E4 could offer comprehensive relief for women experiencing a range of menopause-related discomforts.”

Dr. Utian also referenced a 2017 trial in which estetrol positively impacted lipid profiles, “lowering low-density lipoprotein cholesterol, increasing high-density lipoprotein cholesterol, and showing minimal influence on triglycerides,” he said. “Importantly, estetrol was associated with a significant decrease in osteocalcin levels in the higher dose groups, suggesting a potential preventive effect on bone loss,” he added. A recent review of the overall evidence on estetrol suggests its use is “promising,” Dr. Utian noted.
 

Current trial

His current randomized controlled phase 3 trial included postmenopausal women ages 40-65 from 151 sites in 14 countries in Europe, Latin America, and North America, and Russia. Among the 640 participants in the trial, 213 women randomly received 15 mg of estetrol, 213 women received 20 mg of estetrol, and 214 women received a placebo every day for 3 months. All women without hysterectomies also received 200 mg of progesterone once daily for two weeks after completing the estetrol treatment to protect the endometrium.

Researchers took blood samples from the participants at baseline and week 12 to assess total cholesterol, LDL, HDL, the total cholesterol/HDL ratio, triglycerides, lipoprotein A, fasting plasma glucose, insulin, and A1c.

Compared with women in the placebo group, women in both the 15 mg and 20 mg groups saw a statistically significant decrease in lipoprotein A and in the ratio of total cholesterol to HDL, and a statistically significant increase in HDL. Only the women in the 15 mg group saw a statistically significant decrease in LDL and increase in triglycerides; an increase in triglycerides in the 20 mg group did not reach statistical significance.

Statistically significant decreases in fasting plasma glucose and A1c also occurred in both treatment groups, but a decrease in insulin levels and in the homeostasis model-assessment-estimated insulin resistance (HOMA-IR) seen in both treatment arms did not reach significance.

“While the mean changes after 12 weeks from baseline overall were small changes to the cholesterol and blood sugar profiles, they are clinically meaningful because it suggests that E4 does not have any adverse effects to these measures,” Dr. Shufelt said in an interview. “An advantage is that this gives us another hormone option for vasomotor symptoms since it is a native estrogen with selective tissue.”

It’s too early, however, to determine whether estetrol offers benefits in terms of its safety profile, compared with currently available therapies, Dr. Shufelt said.

”These findings of E4 are similar to how oral estradiol changes lipids, which finds an increase in high-density lipoprotein cholesterol, and decreases plasma concentrations of total and low-density lipoprotein cholesterol. an increase in HDL-C and triglycerides and decrease in LDL-C,” she said.
 

Poster findings also promising

For the findings reported in the poster, researchers assessed quality of life and the clinical meaningfulness of vasomotor symptoms’ reduction at baseline and 12 weeks using the Menopause-Specific Quality of Life (MENQOL) questionnaire and the Clinical Global Impression questionnaire, respectively. They also assessed women’s self-reported genitourinary symptoms, including vaginal dryness, pain during urination, vaginal pain and bleeding related to sex, and vaginal or vulvar irritation or itching. Most of these findings primarily confirmed previous positive effects from E4 in other trials.

Women in both the 15 mg and 20 mg estetrol groups reported a statistically significant improvement at 12 weeks, compared with placebo, in their total MENQOL score and in the vasomotor, psychosocial, and sexual functioning domain scores (P < .05). Those in the 20 mg group also had a statistically significant improvement in their physical domain score (P < .05).

Although numerical improvements in genitourinary symptoms occurred at 12 weeks across all three groups, the only statistically significant difference from baseline occurred in patients taking 15 mg of estetrol, who experienced a decrease in vaginal dryness and vaginal pain during sex (P = .0142 and P = .003, respectively).

The Clinical Global Impression questionnaire asked women at 4 and 12 weeks to rate on a seven-item Likert scale their response to this question: “Rate the total improvement, whether or not in your judgment it is due entirely to drug treatment. Compared to your condition at admission to the study, how much has it changed?” Responses of “very much improved” and “much improved” counted as a clinically meaningful difference.

Compared with 27.9% of patients in the placebo group, 52.9% of patients in the 15 mg group and 59.8% of patients in the 20 mg group rated the weekly frequency of moderate to severe vasomotor symptoms as “much improved” or “very much improved” at 4 weeks (P < .0001). At 12 weeks, those numbers rose to 47% in the placebo group, 73.3% in the 15 mg group and 77.8% in the 20 mg group (P < .0001).

The trial’s primary limitation at this point is having only a 12-week follow-up, Dr. Shufelt said, though a few other questions remain.

“Because the two phase 3 RCTs included hysterectomized and nonhysterectomized women, it was unclear how many women in the study had E4 alone versus E4 with progesterone, as that might play a role in both cholesterol and carbohydrate metabolism,” Dr. Shufelt said. “While baseline data was not presented, it would also be important to know baseline values for the women and confirm that none were on lipid-lowering medications.”

The research was funded by Estetra SRL, an affiliate of Mithra Pharmaceuticals. Dr. Utian is a member of the Mithra and Elektra Scientific Advisory Boards. Dr. Shufelt has no disclosures.
 

Assessing a key aspect of bone architecture, for which clinicians can now be reimbursed under Medicare, can significantly improve the ability to predict a patient’s risk for bone fracture.

Although bone mineral density (BMD) is traditionally used to identify patients with osteoporosis or low bone mass, some physicians have begun incorporating the trabecular bone score (TBS) into their exams.

At the Cleveland Clinic Center for Specialized Women’s Health, factoring in the TBS changed the diagnosis for 16% of 432 patients, according to Holly Thacker, MD, the center’s director.

“Importantly, 11% got worse diagnoses, and I use that in terms of prioritizing treatment,” Dr. Thacker said in an interview. The ability to determine how degraded the bone microarchitecture is through a software system “is a huge advance.”

Dr. Thacker described her center’s experience with the technology at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

While BMD captures the amount of minerals like calcium in the skeleton, TBS assesses the underlying microarchitecture by looking at the distribution of shades of gray on dual-energy x-ray absorptiometry (DXA) scans.

Based on the TBS, patients’ bones are classified as normal, partially degraded, or degraded. Among the 432 patients who received a TBS analysis in 2022, 3% shifted from a normal diagnosis to osteopenia, 8% worsened from osteopenia to osteoporosis, 4% went from osteopenia to normal, and 1.6% downgraded from osteoporosis to osteopenia, Dr. Thacker reported.

The new test may also provide some reassurance for female patients who have thinner bones, which may raise alarms based on BMD. TBS, however, may show that the structure of the bone looks normal.

“When you know that the microarchitecture is normal, you’re a lot less concerned that they actually have a bone disease of osteoporosis,” Dr. Thacker said.

Conversely, unexpectedly degraded bone raises questions.

“That makes you go back and say [to the patient]: ‘Have you been on steroids? Were you malnourished? Is there some other metabolic problem? Have you had some calcium disorder?’ ” Dr. Thacker said.

Dr. Thacker leverages the TBS to help patients obtain effective therapy, typically an anabolic agent followed by antiresorptive medication.

“When I see a patient who not only has osteoporosis on bone density but has completely degraded bone architecture, it’s a lot easier for me to make the argument to the insurance company that this patient is at grave risk for a low trauma fracture and bad outcome without the best treatment,” Dr. Thacker said.
 

10-year-old tech, recently covered

The Food and Drug Administration approved TBS software in 2012, but Medicare only recently started paying for it.

Medimaps Group, a company that markets imaging software to calculate TBS, announced in 2022 that reimbursement from the Centers for Medicare & Medicaid Services was available, at $41.53 on the Physician Fee Schedule and $82.61 on the Hospital Outpatient Prospective Payment Schedule.

“Reimbursement through CMS is an important endorsement of the clinical value of TBS for clinicians and their patients,” Didier Hans, PhD, MBA, the CEO of Medimaps, said in a statement at the time. He noted that more than 600,000 TBS procedures were being performed in the United States each year.

Nevertheless, the initial investment in purchasing the software may be a barrier for health systems.

“We are the first and only site in our health system to offer TBS, as this is an extra expense and not uniformly reimbursed by insurers,” Dr. Thacker reported at the meeting.
 

Potential drawbacks

The TBS software used in Dr. Thacker’s study has been validated only in Asian and White patients between certain ages and weights, meaning the system is not designed to be used for other populations. Other researchers have highlighted a need for trabecular bone scoring to be validated more broadly. The authors of a recent analysis, however, suggest that TBS can be used the same way no matter a patient’s race.

TBS “is going to be most helpful in those with osteopenia who are right near the threshold for treatment,” said Marcella Donovan Walker, MD, MS, in a presentation on bone quality at the meeting.

Many studies have shown that TBS “provides additive information to bone density,” said Dr. Walker, a professor of medicine in the division of endocrinology at Columbia University, New York. For example, a large study of women in Manitoba found that, regardless of whether their bone density was normal, osteopenic, or osteoporotic, those with a low TBS had a much higher risk for fracture.
 

‘Opportunistic screening’ with CT?

TBS relies on the same DXA scans that are used to calculate bone mineral density, so obtaining the score does not add time or radiation to the scanning process, Dr. Thacker said.

But many patients who should receive DXA scans do not, which adds to the promise of “opportunistic screening” for osteoporosis, Dr. Walker said. With this approach, physicians would analyze a CT scan that a patient received for another purpose, such as to investigate abdominal pain or chest pain.

“In these images is information about the bone,” Dr. Walker said.

Researchers have used high-resolution peripheral quantitative CT to perform finite element analysis, where a computer program simulates compression of the bone to create a measure of bone stiffness and determine the load required for a break.

One study found that including those elements predicted fractures better than bone mineral density or the Fracture Risk Assessment Tool alone, Dr. Walker noted.

Other aspects of bone quality include how many cracks are in the bone, the amount of adipose in the marrow space, and the rate at which bone is broken down and rebuilt. But Dr. Walker suggested that the longstanding focus on bone mineral density in clinical practice makes sense.

“By far, bone mass is the most important bone quality,” Dr. Walker said.

Dr. Thacker is the executive director of the nonprofit Speaking of Women’s Health. Dr. Walker reported receiving funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and Amgen.

A version of this article first appeared on Medscape.com.

Assessing a key aspect of bone architecture, for which clinicians can now be reimbursed under Medicare, can significantly improve the ability to predict a patient’s risk for bone fracture.

Although bone mineral density (BMD) is traditionally used to identify patients with osteoporosis or low bone mass, some physicians have begun incorporating the trabecular bone score (TBS) into their exams.

At the Cleveland Clinic Center for Specialized Women’s Health, factoring in the TBS changed the diagnosis for 16% of 432 patients, according to Holly Thacker, MD, the center’s director.

“Importantly, 11% got worse diagnoses, and I use that in terms of prioritizing treatment,” Dr. Thacker said in an interview. The ability to determine how degraded the bone microarchitecture is through a software system “is a huge advance.”

Dr. Thacker described her center’s experience with the technology at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

While BMD captures the amount of minerals like calcium in the skeleton, TBS assesses the underlying microarchitecture by looking at the distribution of shades of gray on dual-energy x-ray absorptiometry (DXA) scans.

Based on the TBS, patients’ bones are classified as normal, partially degraded, or degraded. Among the 432 patients who received a TBS analysis in 2022, 3% shifted from a normal diagnosis to osteopenia, 8% worsened from osteopenia to osteoporosis, 4% went from osteopenia to normal, and 1.6% downgraded from osteoporosis to osteopenia, Dr. Thacker reported.

The new test may also provide some reassurance for female patients who have thinner bones, which may raise alarms based on BMD. TBS, however, may show that the structure of the bone looks normal.

“When you know that the microarchitecture is normal, you’re a lot less concerned that they actually have a bone disease of osteoporosis,” Dr. Thacker said.

Conversely, unexpectedly degraded bone raises questions.

“That makes you go back and say [to the patient]: ‘Have you been on steroids? Were you malnourished? Is there some other metabolic problem? Have you had some calcium disorder?’ ” Dr. Thacker said.

Dr. Thacker leverages the TBS to help patients obtain effective therapy, typically an anabolic agent followed by antiresorptive medication.

“When I see a patient who not only has osteoporosis on bone density but has completely degraded bone architecture, it’s a lot easier for me to make the argument to the insurance company that this patient is at grave risk for a low trauma fracture and bad outcome without the best treatment,” Dr. Thacker said.
 

10-year-old tech, recently covered

The Food and Drug Administration approved TBS software in 2012, but Medicare only recently started paying for it.

Medimaps Group, a company that markets imaging software to calculate TBS, announced in 2022 that reimbursement from the Centers for Medicare & Medicaid Services was available, at $41.53 on the Physician Fee Schedule and $82.61 on the Hospital Outpatient Prospective Payment Schedule.

“Reimbursement through CMS is an important endorsement of the clinical value of TBS for clinicians and their patients,” Didier Hans, PhD, MBA, the CEO of Medimaps, said in a statement at the time. He noted that more than 600,000 TBS procedures were being performed in the United States each year.

Nevertheless, the initial investment in purchasing the software may be a barrier for health systems.

“We are the first and only site in our health system to offer TBS, as this is an extra expense and not uniformly reimbursed by insurers,” Dr. Thacker reported at the meeting.
 

Potential drawbacks

The TBS software used in Dr. Thacker’s study has been validated only in Asian and White patients between certain ages and weights, meaning the system is not designed to be used for other populations. Other researchers have highlighted a need for trabecular bone scoring to be validated more broadly. The authors of a recent analysis, however, suggest that TBS can be used the same way no matter a patient’s race.

TBS “is going to be most helpful in those with osteopenia who are right near the threshold for treatment,” said Marcella Donovan Walker, MD, MS, in a presentation on bone quality at the meeting.

Many studies have shown that TBS “provides additive information to bone density,” said Dr. Walker, a professor of medicine in the division of endocrinology at Columbia University, New York. For example, a large study of women in Manitoba found that, regardless of whether their bone density was normal, osteopenic, or osteoporotic, those with a low TBS had a much higher risk for fracture.
 

‘Opportunistic screening’ with CT?

TBS relies on the same DXA scans that are used to calculate bone mineral density, so obtaining the score does not add time or radiation to the scanning process, Dr. Thacker said.

But many patients who should receive DXA scans do not, which adds to the promise of “opportunistic screening” for osteoporosis, Dr. Walker said. With this approach, physicians would analyze a CT scan that a patient received for another purpose, such as to investigate abdominal pain or chest pain.

“In these images is information about the bone,” Dr. Walker said.

Researchers have used high-resolution peripheral quantitative CT to perform finite element analysis, where a computer program simulates compression of the bone to create a measure of bone stiffness and determine the load required for a break.

One study found that including those elements predicted fractures better than bone mineral density or the Fracture Risk Assessment Tool alone, Dr. Walker noted.

Other aspects of bone quality include how many cracks are in the bone, the amount of adipose in the marrow space, and the rate at which bone is broken down and rebuilt. But Dr. Walker suggested that the longstanding focus on bone mineral density in clinical practice makes sense.

“By far, bone mass is the most important bone quality,” Dr. Walker said.

Dr. Thacker is the executive director of the nonprofit Speaking of Women’s Health. Dr. Walker reported receiving funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and Amgen.

A version of this article first appeared on Medscape.com.

Assessing a key aspect of bone architecture, for which clinicians can now be reimbursed under Medicare, can significantly improve the ability to predict a patient’s risk for bone fracture.

Although bone mineral density (BMD) is traditionally used to identify patients with osteoporosis or low bone mass, some physicians have begun incorporating the trabecular bone score (TBS) into their exams.

At the Cleveland Clinic Center for Specialized Women’s Health, factoring in the TBS changed the diagnosis for 16% of 432 patients, according to Holly Thacker, MD, the center’s director.

“Importantly, 11% got worse diagnoses, and I use that in terms of prioritizing treatment,” Dr. Thacker said in an interview. The ability to determine how degraded the bone microarchitecture is through a software system “is a huge advance.”

Dr. Thacker described her center’s experience with the technology at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

While BMD captures the amount of minerals like calcium in the skeleton, TBS assesses the underlying microarchitecture by looking at the distribution of shades of gray on dual-energy x-ray absorptiometry (DXA) scans.

Based on the TBS, patients’ bones are classified as normal, partially degraded, or degraded. Among the 432 patients who received a TBS analysis in 2022, 3% shifted from a normal diagnosis to osteopenia, 8% worsened from osteopenia to osteoporosis, 4% went from osteopenia to normal, and 1.6% downgraded from osteoporosis to osteopenia, Dr. Thacker reported.

The new test may also provide some reassurance for female patients who have thinner bones, which may raise alarms based on BMD. TBS, however, may show that the structure of the bone looks normal.

“When you know that the microarchitecture is normal, you’re a lot less concerned that they actually have a bone disease of osteoporosis,” Dr. Thacker said.

Conversely, unexpectedly degraded bone raises questions.

“That makes you go back and say [to the patient]: ‘Have you been on steroids? Were you malnourished? Is there some other metabolic problem? Have you had some calcium disorder?’ ” Dr. Thacker said.

Dr. Thacker leverages the TBS to help patients obtain effective therapy, typically an anabolic agent followed by antiresorptive medication.

“When I see a patient who not only has osteoporosis on bone density but has completely degraded bone architecture, it’s a lot easier for me to make the argument to the insurance company that this patient is at grave risk for a low trauma fracture and bad outcome without the best treatment,” Dr. Thacker said.
 

10-year-old tech, recently covered

The Food and Drug Administration approved TBS software in 2012, but Medicare only recently started paying for it.

Medimaps Group, a company that markets imaging software to calculate TBS, announced in 2022 that reimbursement from the Centers for Medicare & Medicaid Services was available, at $41.53 on the Physician Fee Schedule and $82.61 on the Hospital Outpatient Prospective Payment Schedule.

“Reimbursement through CMS is an important endorsement of the clinical value of TBS for clinicians and their patients,” Didier Hans, PhD, MBA, the CEO of Medimaps, said in a statement at the time. He noted that more than 600,000 TBS procedures were being performed in the United States each year.

Nevertheless, the initial investment in purchasing the software may be a barrier for health systems.

“We are the first and only site in our health system to offer TBS, as this is an extra expense and not uniformly reimbursed by insurers,” Dr. Thacker reported at the meeting.
 

Potential drawbacks

The TBS software used in Dr. Thacker’s study has been validated only in Asian and White patients between certain ages and weights, meaning the system is not designed to be used for other populations. Other researchers have highlighted a need for trabecular bone scoring to be validated more broadly. The authors of a recent analysis, however, suggest that TBS can be used the same way no matter a patient’s race.

TBS “is going to be most helpful in those with osteopenia who are right near the threshold for treatment,” said Marcella Donovan Walker, MD, MS, in a presentation on bone quality at the meeting.

Many studies have shown that TBS “provides additive information to bone density,” said Dr. Walker, a professor of medicine in the division of endocrinology at Columbia University, New York. For example, a large study of women in Manitoba found that, regardless of whether their bone density was normal, osteopenic, or osteoporotic, those with a low TBS had a much higher risk for fracture.
 

‘Opportunistic screening’ with CT?

TBS relies on the same DXA scans that are used to calculate bone mineral density, so obtaining the score does not add time or radiation to the scanning process, Dr. Thacker said.

But many patients who should receive DXA scans do not, which adds to the promise of “opportunistic screening” for osteoporosis, Dr. Walker said. With this approach, physicians would analyze a CT scan that a patient received for another purpose, such as to investigate abdominal pain or chest pain.

“In these images is information about the bone,” Dr. Walker said.

Researchers have used high-resolution peripheral quantitative CT to perform finite element analysis, where a computer program simulates compression of the bone to create a measure of bone stiffness and determine the load required for a break.

One study found that including those elements predicted fractures better than bone mineral density or the Fracture Risk Assessment Tool alone, Dr. Walker noted.

Other aspects of bone quality include how many cracks are in the bone, the amount of adipose in the marrow space, and the rate at which bone is broken down and rebuilt. But Dr. Walker suggested that the longstanding focus on bone mineral density in clinical practice makes sense.

“By far, bone mass is the most important bone quality,” Dr. Walker said.

Dr. Thacker is the executive director of the nonprofit Speaking of Women’s Health. Dr. Walker reported receiving funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and Amgen.

A version of this article first appeared on Medscape.com.

WASHINGTON – False negative rates from fine needle aspiration (FNA) biopsies of large thyroid nodules are lower than commonly reported when studies are expanded to include all nodules (including those that were not operated on), compared with only those that were.

While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.

The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.

“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.

The findings were presented at the annual meeting of the American Thyroid Association.
 

Concerns about nodules over 4 cm having high false negative rates

Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.

Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.

“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.

To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.

With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.

Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).

Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.

Overall, the false negative rate including all patients was 4.3%.

“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.

Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.

“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.

In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.

However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.

Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”

In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.

“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.

“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”

Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

WASHINGTON – False negative rates from fine needle aspiration (FNA) biopsies of large thyroid nodules are lower than commonly reported when studies are expanded to include all nodules (including those that were not operated on), compared with only those that were.

While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.

The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.

“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.

The findings were presented at the annual meeting of the American Thyroid Association.
 

Concerns about nodules over 4 cm having high false negative rates

Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.

Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.

“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.

To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.

With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.

Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).

Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.

Overall, the false negative rate including all patients was 4.3%.

“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.

Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.

“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.

In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.

However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.

Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”

In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.

“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.

“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”

Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

WASHINGTON – False negative rates from fine needle aspiration (FNA) biopsies of large thyroid nodules are lower than commonly reported when studies are expanded to include all nodules (including those that were not operated on), compared with only those that were.

While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.

The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.

“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.

The findings were presented at the annual meeting of the American Thyroid Association.
 

Concerns about nodules over 4 cm having high false negative rates

Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.

Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.

“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.

To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.

With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.

Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).

Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.

Overall, the false negative rate including all patients was 4.3%.

“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.

Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.

“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.

In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.

However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.

Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”

In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.

“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.

“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”

Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

HAMBURG, GERMANY – An upcoming joint society statement on hyperglycemic emergencies in adults with diabetes will de-emphasize glucose from the diagnostic criteria for diabetic ketoacidosis (DKA), along with many other updates to the last statement on the topic, published 14 years ago.  

Based on extensive literature reviews and observations of current trends, the new document – due to be published soon – will cover diagnosis and management of the two most serious acute hyperglycemic emergencies seen in adults, DKA and hyperosmolar hyperglycemic state (HHS).

New to the 2023 version will be a strong emphasis on the excess morbidity and mortality risks associated with the increasingly common “hybrid” presentation of the two conditions together, now seen in about a third of cases.

The new report will also more strongly urge clinicians to investigate why the person experienced the emergency.

While new-onset diabetes and infection are recognized precipitating causes for DKA, insulin omission related to finances, mental health, and social determinants should be identified, and patients directed to appropriate resources, said experts previewing the upcoming new report at the annual meeting of the European Association for the Study of Diabetes.

“The challenge is, although we were making progress for a long time in terms of those hyperglycemic crises, we’ve really plateaued and there are still people being admitted in large numbers, and when you look more globally even more so,” said American Diabetes Association Chief Science and Medical Officer Robert A. Gabbay, MD, PhD.

The new consensus report will be jointly endorsed by the ADA, the EASD, the American Association of Clinical Endocrinology, the Diabetes Technology Society, and the Joint British Diabetes Societies for Inpatient Care. The previous consensus statement on the subject was published in 2009 by the ADA alone.
 

New DKA and HHS definitions reflect emerging trends

The statement will revise the definition of DKA, partly spurred by the increasing occurrence and recognition of euglycemic ketoacidosis arising from the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. For all patients with hyperglycemic crisis, the hyperglycemia cutoff is now lowered to 200 mg/dL (11.1 mmol/L) from the previous 250 mg/dL.

However, the glucose cutoff has been removed entirely for people with a history of diabetes.

“Both of these changes are recognizing the wide range of glucose levels at the presence of DKA. Approximately 10% of DKA occurs with euglycemia or near-normoglycemia,” noted coauthor Shivani Misra, MD, PhD, senior clinical lecturer and honorary consultant in Metabolic Medicine at Imperial College, London.

For assessing ketosis in DKA, the new statement strongly recommends use of beta-hydroxybutyrate – either via point-of-care test or serum level measured in a laboratory – with a low cutoff of ≥ 3.0 mmol/L. Alternatively, a urine ketone strip value of 2+ or greater can be used.

However, beta-hydroxybutyrate testing is more widely available now than it was in 2009 and is strongly preferred over urine ketone measurement because it’s the predominant ketone during acidosis. Moreover, urine acetoacetate – measured by the strips – paradoxically increases during resolution of DKA, and drug interferences can occur with urine ketone measurement, Dr. Misra noted.

Metabolic acidosis is now defined as a pH < 7.3 and/or a bicarbonate concentration < 18 mmol/L, up from 15 in some prior guidelines including the United Kingdom’s. Also, anion gap has been removed from the main definition but, the document will say, can still be used in settings where ketone testing is unavailable.

As previously, the new statement will classify DKA by mild, moderate, and severe but now for the first time there are recommendations of care for each of those levels, as well as for HHS.

For HHS, the glucose cutoff of ≥ 600 mg/dL will stay the same. But now, the effective serum osmolality has been lowered from > 320 to > 300 mOsml/L to account for the effect of dehydration, along with an alternative criteria of total serum osmolality > 320 mOsm/L. The same two changes as with DKA for both ketones and acidosis have also been included for HHS.

Asked to comment, session audience member and independent diabetes industry consultant Charles Alexander, MD, told this news organization, “I liked the proposal to eliminate the anion gap in decision-making and to focus on measurement of blood ketones, principally beta-hydroxybutyrate, in the diagnosis of DKA and monitoring the effect of treatment.

“If someone is on an SGLT2 inhibitor, there is no need to look at blood glucose levels, which may be normal or near normal in the setting of DKA.”

But Dr. Alexander thinks that they should have eliminated glucose levels entirely as part of the DKA/HHS definition even for people without diabetes.

“The problem is that medical education for many years has taught us that DKA is a condition of high blood glucose, but it may not be. It is good that they said blood glucose levels were not important if the patient had a history of diabetes. However, a glucose of 200mg/dL may not be low enough if someone is on an SGLT2 inhibitor. There needs to be a much lower threshold for measuring blood ketones in anyone with nausea, vomiting, and abdominal pain, regardless of the blood glucose level.”
 

Acute management: IV fluids, insulin, and potassium

Like the 2009 statement, the new one will include detailed management flowcharts for DKA and HHS, but this time in color. This new statement includes individual algorithms for management with intravenous fluids, insulin, and potassium. Bicarbonate has been removed and relegated to a note at the bottom saying that it should only be considered if pH is < 7.0.

Under fluid treatment, the new statement offers more information about using crystalloids to treat dehydration and a recommendation to add dextrose to IV fluid therapy as a substrate when the glucose drops below 250 mg/dL, in order to prevent hypoglycemia. For euglycemic DKA, the recommendation is to include dextrose and normal saline simultaneously.

And for the first time, subcutaneous rather than IV insulin is considered acceptable for mild, but not moderate or severe, DKA. 

Two options are suggested for IV insulin in HHS: The fluid can be given first and low-dose fixed-rate insulin infusion added, or fluids and insulin can be given at the same time.

Criteria for resolution of DKA are a venous pH of ≥ 7.3 or bicarbonate > 18 mmol/L, ketones < 0.6 mmol/L, and glucose ideally < 200 mg/dL (11.0 mmol/L). For HHS, resolution is suggested when the measured or calculated serum osmolality falls to < 300 mosm/kg, blood glucose is < 250mg/dL (13.9 mmol/L), urine output > 0.5 mL/kg/hour, and cognitive status is improved.

The statement also will provide detailed recommended options for transitioning from IV to subcutaneous insulin, but defers to clinical judgment for deciding when the patient can be discharged. The initiation or continuation of SGLT2 inhibitors is not recommended at any time during hospitalization for hyperglycemic crises.
 

Mitigating complications, preventing recurrence

In addition to listing potential complications of treating hyperglycemic crises, just as the 2009 statement did, the new one will offer mitigation strategies for some of the more common ones. For preventing hypoglycemia, frequent blood glucose monitoring is advised along with adding dextrose to the IV fluids when glucose drops below 250 mg/dL.

For prevention of hypokalemia, which occurs in about half of patients treated for DKA and HHS, the statement recommends potassium monitoring every 4 hours and replacement added to fluids.

Acute kidney injury, also occurring in about half of people treated for DKA and/or HHS, usually resolves with hydration. Daily renal function monitoring is advised.
 

Preventing recurrence: Many factors beyond clinical

Prevention of recurrence with readmission for DKA and/or HHS, occurring in up to 22% of U.S. patients within 30 days, entails close follow-up within 2-4 weeks after discharge (including via telemedicine), and assessment of possible causes, including mental health disorders and social determinants of health.

Appropriate education should be provided, including “structured education” involving problem-solving, sick day rules, injection techniques, a review of insulin doses, consideration of continuous glucose monitoring (CGM), and home ketone testing.  

Patients should be provided with an adequate supply of insulin and durable diabetes equipment, along with contact information for health care professionals who can assist them. Social service professionals can be helpful for patients who lack reliable access.

Dr. Gabbay told this news organization, “The eye-opening thing is we tend to typically think of DKA as how people tend to get diagnosed with diabetes and, yes, that’s true, but that’s only a minority of people. Those might be preventable by early screening, but all these other people and the number of recurrent episodes, that’s an area where it’s really a failure of the system where we can do better in ensuring that doesn’t happen.”

Education is only part of it, he stressed. “It’s not just an intelligence thing. It’s social factors, and there can be complex psychological issues and mental health issues. We need to screen for those things when we see someone coming back the second, third, fifth, or sixth time. We’ve all seen that. Just educating them to take their insulin is not the answer. …You’ve got to ask the questions and engage them to go a little deeper.”

Dr. Gabbay is an employee of the ADA. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation in the United Kingdom.

A version of this article appeared on Medscape.com.

HAMBURG, GERMANY – An upcoming joint society statement on hyperglycemic emergencies in adults with diabetes will de-emphasize glucose from the diagnostic criteria for diabetic ketoacidosis (DKA), along with many other updates to the last statement on the topic, published 14 years ago.  

Based on extensive literature reviews and observations of current trends, the new document – due to be published soon – will cover diagnosis and management of the two most serious acute hyperglycemic emergencies seen in adults, DKA and hyperosmolar hyperglycemic state (HHS).

New to the 2023 version will be a strong emphasis on the excess morbidity and mortality risks associated with the increasingly common “hybrid” presentation of the two conditions together, now seen in about a third of cases.

The new report will also more strongly urge clinicians to investigate why the person experienced the emergency.

While new-onset diabetes and infection are recognized precipitating causes for DKA, insulin omission related to finances, mental health, and social determinants should be identified, and patients directed to appropriate resources, said experts previewing the upcoming new report at the annual meeting of the European Association for the Study of Diabetes.

“The challenge is, although we were making progress for a long time in terms of those hyperglycemic crises, we’ve really plateaued and there are still people being admitted in large numbers, and when you look more globally even more so,” said American Diabetes Association Chief Science and Medical Officer Robert A. Gabbay, MD, PhD.

The new consensus report will be jointly endorsed by the ADA, the EASD, the American Association of Clinical Endocrinology, the Diabetes Technology Society, and the Joint British Diabetes Societies for Inpatient Care. The previous consensus statement on the subject was published in 2009 by the ADA alone.
 

New DKA and HHS definitions reflect emerging trends

The statement will revise the definition of DKA, partly spurred by the increasing occurrence and recognition of euglycemic ketoacidosis arising from the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. For all patients with hyperglycemic crisis, the hyperglycemia cutoff is now lowered to 200 mg/dL (11.1 mmol/L) from the previous 250 mg/dL.

However, the glucose cutoff has been removed entirely for people with a history of diabetes.

“Both of these changes are recognizing the wide range of glucose levels at the presence of DKA. Approximately 10% of DKA occurs with euglycemia or near-normoglycemia,” noted coauthor Shivani Misra, MD, PhD, senior clinical lecturer and honorary consultant in Metabolic Medicine at Imperial College, London.

For assessing ketosis in DKA, the new statement strongly recommends use of beta-hydroxybutyrate – either via point-of-care test or serum level measured in a laboratory – with a low cutoff of ≥ 3.0 mmol/L. Alternatively, a urine ketone strip value of 2+ or greater can be used.

However, beta-hydroxybutyrate testing is more widely available now than it was in 2009 and is strongly preferred over urine ketone measurement because it’s the predominant ketone during acidosis. Moreover, urine acetoacetate – measured by the strips – paradoxically increases during resolution of DKA, and drug interferences can occur with urine ketone measurement, Dr. Misra noted.

Metabolic acidosis is now defined as a pH < 7.3 and/or a bicarbonate concentration < 18 mmol/L, up from 15 in some prior guidelines including the United Kingdom’s. Also, anion gap has been removed from the main definition but, the document will say, can still be used in settings where ketone testing is unavailable.

As previously, the new statement will classify DKA by mild, moderate, and severe but now for the first time there are recommendations of care for each of those levels, as well as for HHS.

For HHS, the glucose cutoff of ≥ 600 mg/dL will stay the same. But now, the effective serum osmolality has been lowered from > 320 to > 300 mOsml/L to account for the effect of dehydration, along with an alternative criteria of total serum osmolality > 320 mOsm/L. The same two changes as with DKA for both ketones and acidosis have also been included for HHS.

Asked to comment, session audience member and independent diabetes industry consultant Charles Alexander, MD, told this news organization, “I liked the proposal to eliminate the anion gap in decision-making and to focus on measurement of blood ketones, principally beta-hydroxybutyrate, in the diagnosis of DKA and monitoring the effect of treatment.

“If someone is on an SGLT2 inhibitor, there is no need to look at blood glucose levels, which may be normal or near normal in the setting of DKA.”

But Dr. Alexander thinks that they should have eliminated glucose levels entirely as part of the DKA/HHS definition even for people without diabetes.

“The problem is that medical education for many years has taught us that DKA is a condition of high blood glucose, but it may not be. It is good that they said blood glucose levels were not important if the patient had a history of diabetes. However, a glucose of 200mg/dL may not be low enough if someone is on an SGLT2 inhibitor. There needs to be a much lower threshold for measuring blood ketones in anyone with nausea, vomiting, and abdominal pain, regardless of the blood glucose level.”
 

Acute management: IV fluids, insulin, and potassium

Like the 2009 statement, the new one will include detailed management flowcharts for DKA and HHS, but this time in color. This new statement includes individual algorithms for management with intravenous fluids, insulin, and potassium. Bicarbonate has been removed and relegated to a note at the bottom saying that it should only be considered if pH is < 7.0.

Under fluid treatment, the new statement offers more information about using crystalloids to treat dehydration and a recommendation to add dextrose to IV fluid therapy as a substrate when the glucose drops below 250 mg/dL, in order to prevent hypoglycemia. For euglycemic DKA, the recommendation is to include dextrose and normal saline simultaneously.

And for the first time, subcutaneous rather than IV insulin is considered acceptable for mild, but not moderate or severe, DKA. 

Two options are suggested for IV insulin in HHS: The fluid can be given first and low-dose fixed-rate insulin infusion added, or fluids and insulin can be given at the same time.

Criteria for resolution of DKA are a venous pH of ≥ 7.3 or bicarbonate > 18 mmol/L, ketones < 0.6 mmol/L, and glucose ideally < 200 mg/dL (11.0 mmol/L). For HHS, resolution is suggested when the measured or calculated serum osmolality falls to < 300 mosm/kg, blood glucose is < 250mg/dL (13.9 mmol/L), urine output > 0.5 mL/kg/hour, and cognitive status is improved.

The statement also will provide detailed recommended options for transitioning from IV to subcutaneous insulin, but defers to clinical judgment for deciding when the patient can be discharged. The initiation or continuation of SGLT2 inhibitors is not recommended at any time during hospitalization for hyperglycemic crises.
 

Mitigating complications, preventing recurrence

In addition to listing potential complications of treating hyperglycemic crises, just as the 2009 statement did, the new one will offer mitigation strategies for some of the more common ones. For preventing hypoglycemia, frequent blood glucose monitoring is advised along with adding dextrose to the IV fluids when glucose drops below 250 mg/dL.

For prevention of hypokalemia, which occurs in about half of patients treated for DKA and HHS, the statement recommends potassium monitoring every 4 hours and replacement added to fluids.

Acute kidney injury, also occurring in about half of people treated for DKA and/or HHS, usually resolves with hydration. Daily renal function monitoring is advised.
 

Preventing recurrence: Many factors beyond clinical

Prevention of recurrence with readmission for DKA and/or HHS, occurring in up to 22% of U.S. patients within 30 days, entails close follow-up within 2-4 weeks after discharge (including via telemedicine), and assessment of possible causes, including mental health disorders and social determinants of health.

Appropriate education should be provided, including “structured education” involving problem-solving, sick day rules, injection techniques, a review of insulin doses, consideration of continuous glucose monitoring (CGM), and home ketone testing.  

Patients should be provided with an adequate supply of insulin and durable diabetes equipment, along with contact information for health care professionals who can assist them. Social service professionals can be helpful for patients who lack reliable access.

Dr. Gabbay told this news organization, “The eye-opening thing is we tend to typically think of DKA as how people tend to get diagnosed with diabetes and, yes, that’s true, but that’s only a minority of people. Those might be preventable by early screening, but all these other people and the number of recurrent episodes, that’s an area where it’s really a failure of the system where we can do better in ensuring that doesn’t happen.”

Education is only part of it, he stressed. “It’s not just an intelligence thing. It’s social factors, and there can be complex psychological issues and mental health issues. We need to screen for those things when we see someone coming back the second, third, fifth, or sixth time. We’ve all seen that. Just educating them to take their insulin is not the answer. …You’ve got to ask the questions and engage them to go a little deeper.”

Dr. Gabbay is an employee of the ADA. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation in the United Kingdom.

A version of this article appeared on Medscape.com.

HAMBURG, GERMANY – An upcoming joint society statement on hyperglycemic emergencies in adults with diabetes will de-emphasize glucose from the diagnostic criteria for diabetic ketoacidosis (DKA), along with many other updates to the last statement on the topic, published 14 years ago.  

Based on extensive literature reviews and observations of current trends, the new document – due to be published soon – will cover diagnosis and management of the two most serious acute hyperglycemic emergencies seen in adults, DKA and hyperosmolar hyperglycemic state (HHS).

New to the 2023 version will be a strong emphasis on the excess morbidity and mortality risks associated with the increasingly common “hybrid” presentation of the two conditions together, now seen in about a third of cases.

The new report will also more strongly urge clinicians to investigate why the person experienced the emergency.

While new-onset diabetes and infection are recognized precipitating causes for DKA, insulin omission related to finances, mental health, and social determinants should be identified, and patients directed to appropriate resources, said experts previewing the upcoming new report at the annual meeting of the European Association for the Study of Diabetes.

“The challenge is, although we were making progress for a long time in terms of those hyperglycemic crises, we’ve really plateaued and there are still people being admitted in large numbers, and when you look more globally even more so,” said American Diabetes Association Chief Science and Medical Officer Robert A. Gabbay, MD, PhD.

The new consensus report will be jointly endorsed by the ADA, the EASD, the American Association of Clinical Endocrinology, the Diabetes Technology Society, and the Joint British Diabetes Societies for Inpatient Care. The previous consensus statement on the subject was published in 2009 by the ADA alone.
 

New DKA and HHS definitions reflect emerging trends

The statement will revise the definition of DKA, partly spurred by the increasing occurrence and recognition of euglycemic ketoacidosis arising from the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. For all patients with hyperglycemic crisis, the hyperglycemia cutoff is now lowered to 200 mg/dL (11.1 mmol/L) from the previous 250 mg/dL.

However, the glucose cutoff has been removed entirely for people with a history of diabetes.

“Both of these changes are recognizing the wide range of glucose levels at the presence of DKA. Approximately 10% of DKA occurs with euglycemia or near-normoglycemia,” noted coauthor Shivani Misra, MD, PhD, senior clinical lecturer and honorary consultant in Metabolic Medicine at Imperial College, London.

For assessing ketosis in DKA, the new statement strongly recommends use of beta-hydroxybutyrate – either via point-of-care test or serum level measured in a laboratory – with a low cutoff of ≥ 3.0 mmol/L. Alternatively, a urine ketone strip value of 2+ or greater can be used.

However, beta-hydroxybutyrate testing is more widely available now than it was in 2009 and is strongly preferred over urine ketone measurement because it’s the predominant ketone during acidosis. Moreover, urine acetoacetate – measured by the strips – paradoxically increases during resolution of DKA, and drug interferences can occur with urine ketone measurement, Dr. Misra noted.

Metabolic acidosis is now defined as a pH < 7.3 and/or a bicarbonate concentration < 18 mmol/L, up from 15 in some prior guidelines including the United Kingdom’s. Also, anion gap has been removed from the main definition but, the document will say, can still be used in settings where ketone testing is unavailable.

As previously, the new statement will classify DKA by mild, moderate, and severe but now for the first time there are recommendations of care for each of those levels, as well as for HHS.

For HHS, the glucose cutoff of ≥ 600 mg/dL will stay the same. But now, the effective serum osmolality has been lowered from > 320 to > 300 mOsml/L to account for the effect of dehydration, along with an alternative criteria of total serum osmolality > 320 mOsm/L. The same two changes as with DKA for both ketones and acidosis have also been included for HHS.

Asked to comment, session audience member and independent diabetes industry consultant Charles Alexander, MD, told this news organization, “I liked the proposal to eliminate the anion gap in decision-making and to focus on measurement of blood ketones, principally beta-hydroxybutyrate, in the diagnosis of DKA and monitoring the effect of treatment.

“If someone is on an SGLT2 inhibitor, there is no need to look at blood glucose levels, which may be normal or near normal in the setting of DKA.”

But Dr. Alexander thinks that they should have eliminated glucose levels entirely as part of the DKA/HHS definition even for people without diabetes.

“The problem is that medical education for many years has taught us that DKA is a condition of high blood glucose, but it may not be. It is good that they said blood glucose levels were not important if the patient had a history of diabetes. However, a glucose of 200mg/dL may not be low enough if someone is on an SGLT2 inhibitor. There needs to be a much lower threshold for measuring blood ketones in anyone with nausea, vomiting, and abdominal pain, regardless of the blood glucose level.”
 

Acute management: IV fluids, insulin, and potassium

Like the 2009 statement, the new one will include detailed management flowcharts for DKA and HHS, but this time in color. This new statement includes individual algorithms for management with intravenous fluids, insulin, and potassium. Bicarbonate has been removed and relegated to a note at the bottom saying that it should only be considered if pH is < 7.0.

Under fluid treatment, the new statement offers more information about using crystalloids to treat dehydration and a recommendation to add dextrose to IV fluid therapy as a substrate when the glucose drops below 250 mg/dL, in order to prevent hypoglycemia. For euglycemic DKA, the recommendation is to include dextrose and normal saline simultaneously.

And for the first time, subcutaneous rather than IV insulin is considered acceptable for mild, but not moderate or severe, DKA. 

Two options are suggested for IV insulin in HHS: The fluid can be given first and low-dose fixed-rate insulin infusion added, or fluids and insulin can be given at the same time.

Criteria for resolution of DKA are a venous pH of ≥ 7.3 or bicarbonate > 18 mmol/L, ketones < 0.6 mmol/L, and glucose ideally < 200 mg/dL (11.0 mmol/L). For HHS, resolution is suggested when the measured or calculated serum osmolality falls to < 300 mosm/kg, blood glucose is < 250mg/dL (13.9 mmol/L), urine output > 0.5 mL/kg/hour, and cognitive status is improved.

The statement also will provide detailed recommended options for transitioning from IV to subcutaneous insulin, but defers to clinical judgment for deciding when the patient can be discharged. The initiation or continuation of SGLT2 inhibitors is not recommended at any time during hospitalization for hyperglycemic crises.
 

Mitigating complications, preventing recurrence

In addition to listing potential complications of treating hyperglycemic crises, just as the 2009 statement did, the new one will offer mitigation strategies for some of the more common ones. For preventing hypoglycemia, frequent blood glucose monitoring is advised along with adding dextrose to the IV fluids when glucose drops below 250 mg/dL.

For prevention of hypokalemia, which occurs in about half of patients treated for DKA and HHS, the statement recommends potassium monitoring every 4 hours and replacement added to fluids.

Acute kidney injury, also occurring in about half of people treated for DKA and/or HHS, usually resolves with hydration. Daily renal function monitoring is advised.
 

Preventing recurrence: Many factors beyond clinical

Prevention of recurrence with readmission for DKA and/or HHS, occurring in up to 22% of U.S. patients within 30 days, entails close follow-up within 2-4 weeks after discharge (including via telemedicine), and assessment of possible causes, including mental health disorders and social determinants of health.

Appropriate education should be provided, including “structured education” involving problem-solving, sick day rules, injection techniques, a review of insulin doses, consideration of continuous glucose monitoring (CGM), and home ketone testing.  

Patients should be provided with an adequate supply of insulin and durable diabetes equipment, along with contact information for health care professionals who can assist them. Social service professionals can be helpful for patients who lack reliable access.

Dr. Gabbay told this news organization, “The eye-opening thing is we tend to typically think of DKA as how people tend to get diagnosed with diabetes and, yes, that’s true, but that’s only a minority of people. Those might be preventable by early screening, but all these other people and the number of recurrent episodes, that’s an area where it’s really a failure of the system where we can do better in ensuring that doesn’t happen.”

Education is only part of it, he stressed. “It’s not just an intelligence thing. It’s social factors, and there can be complex psychological issues and mental health issues. We need to screen for those things when we see someone coming back the second, third, fifth, or sixth time. We’ve all seen that. Just educating them to take their insulin is not the answer. …You’ve got to ask the questions and engage them to go a little deeper.”

Dr. Gabbay is an employee of the ADA. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation in the United Kingdom.

A version of this article appeared on Medscape.com.

Thyroxine and L-thyroxine are two of the 10 most frequently prescribed medicinal products. “One large health insurance company ranks thyroid hormone at fourth place in the list of most-sold medications in the United States. It is possibly the second most commonly prescribed preparation,” said Joachim Feldkamp, MD, PhD, director of the University Clinic for General Internal Medicine, Endocrinology, Diabetology, and Infectious Diseases at Central Hospital, Bielefeld, Germany, at the online press conference for the German Society of Endocrinology’s hormone week.

The preparation is prescribed when the thyroid gland produces too little thyroid hormone. The messenger substance thyroid-stimulating hormone (TSH) is used as a screening value to assess thyroid function. An increase in TSH can indicate that too little thyroid hormone is being produced.

“But this does not mean that an underactive thyroid gland is hiding behind every elevated TSH value,” said Dr. Feldkamp. Normally, the TSH value lies between 0.3 and 4.2 mU/L. “Hypothyroidism, as it’s known, is formally present if the TSH value lies above the upper limit of 4.2 mU/L,” said Dr. Feldkamp.
 

Check again

However, not every elevated TSH value needs to be treated immediately. “From large-scale investigations, we know that TSH values are subject to fluctuations,” said Dr. Feldkamp. Individual measurements must therefore be taken with a grain of salt and almost never justify a therapeutic decision. Therefore, a slightly elevated TSH value should be checked again 2-6 months later, and the patient should be asked if they are experiencing any symptoms. “In 50%-60% of cases, the TSH value normalized at the second checkup without requiring any treatment,” Dr. Feldkamp explained.

The TSH value could be elevated for several reasons:

• Fluctuations depending on the time of day. At night and early in the morning, the TSH value is much higher than in the afternoon. An acute lack of sleep can lead to higher TSH values in the morning.
• Fluctuations depending on the time of year. In winter, TSH values are slightly higher than in the summer owing to adaptation to cooler temperatures. Researchers in the Arctic, for example, have significantly higher TSH values than people who live in warmer regions.
• Age-dependent differences. Children and adolescents have higher TSH values than adults do. The TSH values of adolescents cannot be based on those of adults because this would lead to incorrect treatment. In addition, TSH values increase with age, and slightly elevated values are initially no cause for treatment in people aged 70-80 years. Caution is advised during treatment, because overtreatment can lead to cardiac arrhythmias and a decrease in bone density.
• Sex-specific differences. The TSH values of women are generally a little higher than those in men.
• Obesity. In obesity, TSH increases and often exceeds the normal values usually recorded in persons of normal weight. The elevated values do not reflect a state of hypofunction but rather the body’s adjustment mechanism. If these patients lose weight, the TSH values will drop spontaneously. Slightly elevated TSH values in obese people should not be treated with thyroid hormones.

The nutritional supplement biotin (vitamin H or vitamin B7), which is often taken for skin, hair, and nail growth disorders, can distort measured values. In many of the laboratory methods used, the biotin competes with the test substances used. As a result, it can lead to falsely high and falsely low TSH values. At high doses of biotin (for example, 10 mg), there should be at least a 3-day pause (and ideally a pause of 1 week) before measuring TSH.
 

Hasty prescriptions

“Sometimes, because of the assumption that every high TSH value is due to sickness-related hypothyroidism, thyroid hormones can be prescribed too quickly,” said Dr. Feldkamp. This is also true for patients with thyroid nodules due to iodine deficiency, who are often still treated with thyroid hormones.

“These days, because we are generally an iodine-deficient nation, iodine would potentially be given in combination with thyroid hormones but not with thyroid hormones alone. There are lots of patients who have been taking thyroid hormones for 30 or 40 years due to thyroid nodules. That should definitely be reviewed,” said Dr. Feldkamp.
 

When to treat?

Dr. Feldkamp does not believe that standard determination of the TSH value is sensible and advises that clinicians examine patients with newly occurring symptoms, such as excess weight, impaired weight regulation despite reduced appetite, depression, or a high need for sleep.

If there are symptoms, the thyroid function must be clarified further. “This includes determination of free thyroid hormones T3 and T4; detection of antibodies against autologous thyroid tissue such as TPO-Ab [antibody against thyroid peroxidase], TG-Ab [antibody against thyroglobulin], and TRAb [antibody against TSH receptor]; and ultrasound examination of the metabolic organ,” said Dr. Feldkamp. Autoimmune-related hypothyroidism (Hashimoto’s thyroiditis) is the most common cause of an overly high TSH level.

Treatment should take place in the following situations:

• In young patients with TSH values greater than 10 mU/L;
• In young (< 65 years) symptomatic patients with TSH values of 4 to less than 10 mU/L;
• With elevated TSH values that result from thyroid surgery or radioactive iodine therapy;
• In patients with a diffuse enlarged or severely nodular thyroid gland
• In pregnant women with elevated TSH values.

This article was translated from Medscape’s German Edition and a version appeared on Medscape.com.

Thyroxine and L-thyroxine are two of the 10 most frequently prescribed medicinal products. “One large health insurance company ranks thyroid hormone at fourth place in the list of most-sold medications in the United States. It is possibly the second most commonly prescribed preparation,” said Joachim Feldkamp, MD, PhD, director of the University Clinic for General Internal Medicine, Endocrinology, Diabetology, and Infectious Diseases at Central Hospital, Bielefeld, Germany, at the online press conference for the German Society of Endocrinology’s hormone week.

The preparation is prescribed when the thyroid gland produces too little thyroid hormone. The messenger substance thyroid-stimulating hormone (TSH) is used as a screening value to assess thyroid function. An increase in TSH can indicate that too little thyroid hormone is being produced.

“But this does not mean that an underactive thyroid gland is hiding behind every elevated TSH value,” said Dr. Feldkamp. Normally, the TSH value lies between 0.3 and 4.2 mU/L. “Hypothyroidism, as it’s known, is formally present if the TSH value lies above the upper limit of 4.2 mU/L,” said Dr. Feldkamp.
 

Check again

However, not every elevated TSH value needs to be treated immediately. “From large-scale investigations, we know that TSH values are subject to fluctuations,” said Dr. Feldkamp. Individual measurements must therefore be taken with a grain of salt and almost never justify a therapeutic decision. Therefore, a slightly elevated TSH value should be checked again 2-6 months later, and the patient should be asked if they are experiencing any symptoms. “In 50%-60% of cases, the TSH value normalized at the second checkup without requiring any treatment,” Dr. Feldkamp explained.

The TSH value could be elevated for several reasons:

• Fluctuations depending on the time of day. At night and early in the morning, the TSH value is much higher than in the afternoon. An acute lack of sleep can lead to higher TSH values in the morning.
• Fluctuations depending on the time of year. In winter, TSH values are slightly higher than in the summer owing to adaptation to cooler temperatures. Researchers in the Arctic, for example, have significantly higher TSH values than people who live in warmer regions.
• Age-dependent differences. Children and adolescents have higher TSH values than adults do. The TSH values of adolescents cannot be based on those of adults because this would lead to incorrect treatment. In addition, TSH values increase with age, and slightly elevated values are initially no cause for treatment in people aged 70-80 years. Caution is advised during treatment, because overtreatment can lead to cardiac arrhythmias and a decrease in bone density.
• Sex-specific differences. The TSH values of women are generally a little higher than those in men.
• Obesity. In obesity, TSH increases and often exceeds the normal values usually recorded in persons of normal weight. The elevated values do not reflect a state of hypofunction but rather the body’s adjustment mechanism. If these patients lose weight, the TSH values will drop spontaneously. Slightly elevated TSH values in obese people should not be treated with thyroid hormones.

The nutritional supplement biotin (vitamin H or vitamin B7), which is often taken for skin, hair, and nail growth disorders, can distort measured values. In many of the laboratory methods used, the biotin competes with the test substances used. As a result, it can lead to falsely high and falsely low TSH values. At high doses of biotin (for example, 10 mg), there should be at least a 3-day pause (and ideally a pause of 1 week) before measuring TSH.
 

Hasty prescriptions

“Sometimes, because of the assumption that every high TSH value is due to sickness-related hypothyroidism, thyroid hormones can be prescribed too quickly,” said Dr. Feldkamp. This is also true for patients with thyroid nodules due to iodine deficiency, who are often still treated with thyroid hormones.

“These days, because we are generally an iodine-deficient nation, iodine would potentially be given in combination with thyroid hormones but not with thyroid hormones alone. There are lots of patients who have been taking thyroid hormones for 30 or 40 years due to thyroid nodules. That should definitely be reviewed,” said Dr. Feldkamp.
 

When to treat?

Dr. Feldkamp does not believe that standard determination of the TSH value is sensible and advises that clinicians examine patients with newly occurring symptoms, such as excess weight, impaired weight regulation despite reduced appetite, depression, or a high need for sleep.

If there are symptoms, the thyroid function must be clarified further. “This includes determination of free thyroid hormones T3 and T4; detection of antibodies against autologous thyroid tissue such as TPO-Ab [antibody against thyroid peroxidase], TG-Ab [antibody against thyroglobulin], and TRAb [antibody against TSH receptor]; and ultrasound examination of the metabolic organ,” said Dr. Feldkamp. Autoimmune-related hypothyroidism (Hashimoto’s thyroiditis) is the most common cause of an overly high TSH level.

Treatment should take place in the following situations:

• In young patients with TSH values greater than 10 mU/L;
• In young (< 65 years) symptomatic patients with TSH values of 4 to less than 10 mU/L;
• With elevated TSH values that result from thyroid surgery or radioactive iodine therapy;
• In patients with a diffuse enlarged or severely nodular thyroid gland
• In pregnant women with elevated TSH values.

This article was translated from Medscape’s German Edition and a version appeared on Medscape.com.

Thyroxine and L-thyroxine are two of the 10 most frequently prescribed medicinal products. “One large health insurance company ranks thyroid hormone at fourth place in the list of most-sold medications in the United States. It is possibly the second most commonly prescribed preparation,” said Joachim Feldkamp, MD, PhD, director of the University Clinic for General Internal Medicine, Endocrinology, Diabetology, and Infectious Diseases at Central Hospital, Bielefeld, Germany, at the online press conference for the German Society of Endocrinology’s hormone week.

The preparation is prescribed when the thyroid gland produces too little thyroid hormone. The messenger substance thyroid-stimulating hormone (TSH) is used as a screening value to assess thyroid function. An increase in TSH can indicate that too little thyroid hormone is being produced.

“But this does not mean that an underactive thyroid gland is hiding behind every elevated TSH value,” said Dr. Feldkamp. Normally, the TSH value lies between 0.3 and 4.2 mU/L. “Hypothyroidism, as it’s known, is formally present if the TSH value lies above the upper limit of 4.2 mU/L,” said Dr. Feldkamp.
 

Check again

However, not every elevated TSH value needs to be treated immediately. “From large-scale investigations, we know that TSH values are subject to fluctuations,” said Dr. Feldkamp. Individual measurements must therefore be taken with a grain of salt and almost never justify a therapeutic decision. Therefore, a slightly elevated TSH value should be checked again 2-6 months later, and the patient should be asked if they are experiencing any symptoms. “In 50%-60% of cases, the TSH value normalized at the second checkup without requiring any treatment,” Dr. Feldkamp explained.

The TSH value could be elevated for several reasons:

• Fluctuations depending on the time of day. At night and early in the morning, the TSH value is much higher than in the afternoon. An acute lack of sleep can lead to higher TSH values in the morning.
• Fluctuations depending on the time of year. In winter, TSH values are slightly higher than in the summer owing to adaptation to cooler temperatures. Researchers in the Arctic, for example, have significantly higher TSH values than people who live in warmer regions.
• Age-dependent differences. Children and adolescents have higher TSH values than adults do. The TSH values of adolescents cannot be based on those of adults because this would lead to incorrect treatment. In addition, TSH values increase with age, and slightly elevated values are initially no cause for treatment in people aged 70-80 years. Caution is advised during treatment, because overtreatment can lead to cardiac arrhythmias and a decrease in bone density.
• Sex-specific differences. The TSH values of women are generally a little higher than those in men.
• Obesity. In obesity, TSH increases and often exceeds the normal values usually recorded in persons of normal weight. The elevated values do not reflect a state of hypofunction but rather the body’s adjustment mechanism. If these patients lose weight, the TSH values will drop spontaneously. Slightly elevated TSH values in obese people should not be treated with thyroid hormones.

The nutritional supplement biotin (vitamin H or vitamin B7), which is often taken for skin, hair, and nail growth disorders, can distort measured values. In many of the laboratory methods used, the biotin competes with the test substances used. As a result, it can lead to falsely high and falsely low TSH values. At high doses of biotin (for example, 10 mg), there should be at least a 3-day pause (and ideally a pause of 1 week) before measuring TSH.
 

Hasty prescriptions

“Sometimes, because of the assumption that every high TSH value is due to sickness-related hypothyroidism, thyroid hormones can be prescribed too quickly,” said Dr. Feldkamp. This is also true for patients with thyroid nodules due to iodine deficiency, who are often still treated with thyroid hormones.

“These days, because we are generally an iodine-deficient nation, iodine would potentially be given in combination with thyroid hormones but not with thyroid hormones alone. There are lots of patients who have been taking thyroid hormones for 30 or 40 years due to thyroid nodules. That should definitely be reviewed,” said Dr. Feldkamp.
 

When to treat?

Dr. Feldkamp does not believe that standard determination of the TSH value is sensible and advises that clinicians examine patients with newly occurring symptoms, such as excess weight, impaired weight regulation despite reduced appetite, depression, or a high need for sleep.

If there are symptoms, the thyroid function must be clarified further. “This includes determination of free thyroid hormones T3 and T4; detection of antibodies against autologous thyroid tissue such as TPO-Ab [antibody against thyroid peroxidase], TG-Ab [antibody against thyroglobulin], and TRAb [antibody against TSH receptor]; and ultrasound examination of the metabolic organ,” said Dr. Feldkamp. Autoimmune-related hypothyroidism (Hashimoto’s thyroiditis) is the most common cause of an overly high TSH level.

Treatment should take place in the following situations:

• In young patients with TSH values greater than 10 mU/L;
• In young (< 65 years) symptomatic patients with TSH values of 4 to less than 10 mU/L;
• With elevated TSH values that result from thyroid surgery or radioactive iodine therapy;
• In patients with a diffuse enlarged or severely nodular thyroid gland
• In pregnant women with elevated TSH values.

This article was translated from Medscape’s German Edition and a version appeared on Medscape.com.