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Fast foods contain endocrine-disrupting chemicals
, such as chicken nuggets, hamburgers, and cheese pizza, new research suggests.
The first-of-its-kind study, which measured concentrations of chemicals such as phthalates in foods and gloves from U.S. fast food chains, is also the first to detect the plasticizer DEHT in fast foods.
“We knew from prior research that fast food consumption is linked to higher levels of phthalates in people’s bodies, but our study was novel because we actually collected these food items from fast food places and measured them,” said study author Lariah Edwards, PhD, a postdoctoral research scientist at the Milken Institute School of Public Health, George Washington University, Washington.
“Our research added an additional piece of information to the puzzle,” Dr. Edwards said in an interview.
A class of chemicals used in food packaging and food processing equipment, phthalates such as DEHP and DnBP, can leach out of these items and interfere with hormone production, Dr. Edwards said. They are linked with a wide variety of reproductive, developmental, brain, and immune effects, as well as with childhood obesity, asthma, cancer, and cardiovascular problems.
Meanwhile, nonphthalate or replacement plasticizers have been used in place of phthalates, some of which have been banned in certain products. But these plasticizers aren’t well studied, Dr. Edwards said, making the detection of DEHT in fast foods particularly concerning.
“There’s very limited research out there to understand the human health effects” of DEHT in food, she said, “so we’re being exposed before we understand what it’s doing to our health. It’s almost like we’re setting ourselves up for a big experiment.”
The study was recently published in the Journal of Exposure Science & Environmental Epidemiology .
Fast foods containing meat had highest concentrations of chemicals
Dr. Edwards and colleagues obtained 64 food samples, including hamburgers, fries, chicken nuggets, chicken burritos, and cheese pizza, as well as three pairs of unused gloves from six different fast food restaurants in San Antonio.
Using gas chromatography–mass spectrometry, they analyzed the samples for 11 chemicals, including eight phthalates and three replacement plasticizers.
The researchers detected 10 of the 11 chemicals in fast food samples: 81% of foods contained DnBP (di-n-butyl phthalate), and 70% contained DEHP (di(2-ethylhexyl phthalate)). Meanwhile 86% of samples contained replacement plasticizer DEHT (di(2-ethylhexyl terephthalate)).
Overall, fast food samples containing meat — including chicken nuggets, chicken burritos, and hamburgers — contained higher levels of these chemicals, Dr. Edwards noted.
“We know fast food is not the most nutritious, and now we’re seeing these chemicals in it we shouldn’t be exposed to,” she said.
The results also create implications for health equity, Dr. Edwards said, as Black people in the United States report eating more fast foods than other racial and ethnic groups for many reasons, such as longstanding residential segregation.
Many advocacy groups are pushing for stronger regulations on phthalates in foods, she said, and the study can be used to fuel those efforts.
“We’re hoping our findings help people understand what they’re eating and what’s in food,” Dr. Edwards said. “If they want to reduce exposure to phthalates in fast food, they can choose foods without meat in them. But not everyone has the option of reducing fast food consumption — personal choice is important, but policy is what’s going to protect us.”
Dr. Edwards noted that the research was limited by small sample sizes gathered in one U.S. city. Limitations in extraction methods also meant the researchers were able to detect chemicals in gloves only at high concentrations.
“That being said, I do think our results are fairly generalizable,” she added, “because the way fast foods are prepared at these restaurants is fairly consistent.”
The study was funded by the Passport Foundation, Forsythia Foundation, and Marisla Foundation. Dr. Edwards has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, such as chicken nuggets, hamburgers, and cheese pizza, new research suggests.
The first-of-its-kind study, which measured concentrations of chemicals such as phthalates in foods and gloves from U.S. fast food chains, is also the first to detect the plasticizer DEHT in fast foods.
“We knew from prior research that fast food consumption is linked to higher levels of phthalates in people’s bodies, but our study was novel because we actually collected these food items from fast food places and measured them,” said study author Lariah Edwards, PhD, a postdoctoral research scientist at the Milken Institute School of Public Health, George Washington University, Washington.
“Our research added an additional piece of information to the puzzle,” Dr. Edwards said in an interview.
A class of chemicals used in food packaging and food processing equipment, phthalates such as DEHP and DnBP, can leach out of these items and interfere with hormone production, Dr. Edwards said. They are linked with a wide variety of reproductive, developmental, brain, and immune effects, as well as with childhood obesity, asthma, cancer, and cardiovascular problems.
Meanwhile, nonphthalate or replacement plasticizers have been used in place of phthalates, some of which have been banned in certain products. But these plasticizers aren’t well studied, Dr. Edwards said, making the detection of DEHT in fast foods particularly concerning.
“There’s very limited research out there to understand the human health effects” of DEHT in food, she said, “so we’re being exposed before we understand what it’s doing to our health. It’s almost like we’re setting ourselves up for a big experiment.”
The study was recently published in the Journal of Exposure Science & Environmental Epidemiology .
Fast foods containing meat had highest concentrations of chemicals
Dr. Edwards and colleagues obtained 64 food samples, including hamburgers, fries, chicken nuggets, chicken burritos, and cheese pizza, as well as three pairs of unused gloves from six different fast food restaurants in San Antonio.
Using gas chromatography–mass spectrometry, they analyzed the samples for 11 chemicals, including eight phthalates and three replacement plasticizers.
The researchers detected 10 of the 11 chemicals in fast food samples: 81% of foods contained DnBP (di-n-butyl phthalate), and 70% contained DEHP (di(2-ethylhexyl phthalate)). Meanwhile 86% of samples contained replacement plasticizer DEHT (di(2-ethylhexyl terephthalate)).
Overall, fast food samples containing meat — including chicken nuggets, chicken burritos, and hamburgers — contained higher levels of these chemicals, Dr. Edwards noted.
“We know fast food is not the most nutritious, and now we’re seeing these chemicals in it we shouldn’t be exposed to,” she said.
The results also create implications for health equity, Dr. Edwards said, as Black people in the United States report eating more fast foods than other racial and ethnic groups for many reasons, such as longstanding residential segregation.
Many advocacy groups are pushing for stronger regulations on phthalates in foods, she said, and the study can be used to fuel those efforts.
“We’re hoping our findings help people understand what they’re eating and what’s in food,” Dr. Edwards said. “If they want to reduce exposure to phthalates in fast food, they can choose foods without meat in them. But not everyone has the option of reducing fast food consumption — personal choice is important, but policy is what’s going to protect us.”
Dr. Edwards noted that the research was limited by small sample sizes gathered in one U.S. city. Limitations in extraction methods also meant the researchers were able to detect chemicals in gloves only at high concentrations.
“That being said, I do think our results are fairly generalizable,” she added, “because the way fast foods are prepared at these restaurants is fairly consistent.”
The study was funded by the Passport Foundation, Forsythia Foundation, and Marisla Foundation. Dr. Edwards has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, such as chicken nuggets, hamburgers, and cheese pizza, new research suggests.
The first-of-its-kind study, which measured concentrations of chemicals such as phthalates in foods and gloves from U.S. fast food chains, is also the first to detect the plasticizer DEHT in fast foods.
“We knew from prior research that fast food consumption is linked to higher levels of phthalates in people’s bodies, but our study was novel because we actually collected these food items from fast food places and measured them,” said study author Lariah Edwards, PhD, a postdoctoral research scientist at the Milken Institute School of Public Health, George Washington University, Washington.
“Our research added an additional piece of information to the puzzle,” Dr. Edwards said in an interview.
A class of chemicals used in food packaging and food processing equipment, phthalates such as DEHP and DnBP, can leach out of these items and interfere with hormone production, Dr. Edwards said. They are linked with a wide variety of reproductive, developmental, brain, and immune effects, as well as with childhood obesity, asthma, cancer, and cardiovascular problems.
Meanwhile, nonphthalate or replacement plasticizers have been used in place of phthalates, some of which have been banned in certain products. But these plasticizers aren’t well studied, Dr. Edwards said, making the detection of DEHT in fast foods particularly concerning.
“There’s very limited research out there to understand the human health effects” of DEHT in food, she said, “so we’re being exposed before we understand what it’s doing to our health. It’s almost like we’re setting ourselves up for a big experiment.”
The study was recently published in the Journal of Exposure Science & Environmental Epidemiology .
Fast foods containing meat had highest concentrations of chemicals
Dr. Edwards and colleagues obtained 64 food samples, including hamburgers, fries, chicken nuggets, chicken burritos, and cheese pizza, as well as three pairs of unused gloves from six different fast food restaurants in San Antonio.
Using gas chromatography–mass spectrometry, they analyzed the samples for 11 chemicals, including eight phthalates and three replacement plasticizers.
The researchers detected 10 of the 11 chemicals in fast food samples: 81% of foods contained DnBP (di-n-butyl phthalate), and 70% contained DEHP (di(2-ethylhexyl phthalate)). Meanwhile 86% of samples contained replacement plasticizer DEHT (di(2-ethylhexyl terephthalate)).
Overall, fast food samples containing meat — including chicken nuggets, chicken burritos, and hamburgers — contained higher levels of these chemicals, Dr. Edwards noted.
“We know fast food is not the most nutritious, and now we’re seeing these chemicals in it we shouldn’t be exposed to,” she said.
The results also create implications for health equity, Dr. Edwards said, as Black people in the United States report eating more fast foods than other racial and ethnic groups for many reasons, such as longstanding residential segregation.
Many advocacy groups are pushing for stronger regulations on phthalates in foods, she said, and the study can be used to fuel those efforts.
“We’re hoping our findings help people understand what they’re eating and what’s in food,” Dr. Edwards said. “If they want to reduce exposure to phthalates in fast food, they can choose foods without meat in them. But not everyone has the option of reducing fast food consumption — personal choice is important, but policy is what’s going to protect us.”
Dr. Edwards noted that the research was limited by small sample sizes gathered in one U.S. city. Limitations in extraction methods also meant the researchers were able to detect chemicals in gloves only at high concentrations.
“That being said, I do think our results are fairly generalizable,” she added, “because the way fast foods are prepared at these restaurants is fairly consistent.”
The study was funded by the Passport Foundation, Forsythia Foundation, and Marisla Foundation. Dr. Edwards has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF EXPOSURE SCIENCE & ENVIRONMENTAL EPIDEMIOLOGY
Evaluating phantom hCG and low-level hCG elevations in the nonpregnant patient
A human chorionic gonadotropin (hCG) test is commonly ordered by gynecologists prior to surgical procedures, in the workup of bleeding abnormalities, and in the follow-up of ectopic and molar pregnancies, to name a few indications. In doing so, occasionally clinicians will find themselves in the diagnostic dilemma of discovering an inexplicable low-level elevation in hCG, such as in a postmenopausal patient. This clinical picture can be confusing and can be concerning for conditions such as postmolar gestational trophoblastic neoplasia (GTN). However, there can be benign causes of this phenomenon.1 To prevent unnecessary worry, investigation of treatments is important. In fact, misdiagnosis and inappropriate treatment of benign, low-level hCG levels with unnecessary chemotherapy is problematic mismanagement of gestational trophoblastic disease (GTD), and a major cause of litigation.
Human chorionic gonadotropin is a glycoprotein hormone with two subunits (alpha and beta). It can come from multiple sources, including trophoblastic cells, malignant trophoblastic cells, the pituitary gland, and exogenous sources.1 Its alpha-subunit is identical to that of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH). Its beta-subunit is unique, though very similar to that of LH. The free hCG beta subunit can be produced by nontrophoblastic neoplasms. The gene for the beta subunit of hCG is in close proximity to the beta subunit of LH and increases in gonadotropin-releasing hormone (GnRH) in menopause can result in the stimulation of both genes. Understanding the sources of hCG-like glycoproteins and mechanisms for testing is important when considering possible causes for falsely elevated hCG.
Most commercially available serum hCG assays detect normal intact hCG and free beta subunits. They are typically sandwich assays utilizing antibody binding sites in which a solid-phase anti-hCG antibody to a specific hCG target is then mixed with the patient’s serum, trapping or binding the hCG, which is then treated with an indicator antibody. After being washed with the indicator or “capture” antibody, its relative (quantitative) levels can be measured.1
Urine hCG testing (such as urine pregnancy tests) work through capillary action, drawing the patient’s urine across absorbent pads before reaching a pad which contains anti-hCG antibodies (the detection zone) in the test line. These tests are less sensitive than serum tests, but many can detect hCG levels <15-20 mIU/mL.1
When ob.gyns. are asked to consult on or evaluate persistently low-level elevations of hCG in nonpregnant patients they should consider both malignant and nonmalignant etiologies. Malignant causes include GTN or quiescent GTD (e.g., after treatment of a molar pregnancy or GTN), choriocarcinoma (e.g., ovarian germ cell tumors), and nonchoriocarcinoma malignancies (such as cervical, pancreatic, breast, renal). Nonmalignant causes of hCG elevations in nonpregnant patients include pituitary hCG (in postmenopausal patients), exogenous hCG, and phantom hCG.
The first step in diagnostic workup is to perform a urine pregnancy test. Provided that the serum hCG level is > 20 mIU/mL, the urine HCG should be positive unless the cause of elevated levels is “phantom hCG” from heterophilic antibodies. When patients are exposed to animal antigens (such as in vaccines) they can develop antibodies such as human anti-mouse antibody. These antibodies have affinity to the binding antibodies used in many hCG sandwich assays and form a linkage between the solid phase antibody and the detection antibody creating a false-positive result. This false-positive test is only present in serum testing but not urine tests because the patient’s heterophilic antibodies are not excreted by the kidney and thus not available to create a false-positive result. An alternative method to make the diagnosis of phantom hCG is to request that the hCG testing be run at a different lab with a different assay (which may not react with the same affinity to the patient’s anti-animal heterophile antibodies), or to request that the lab perform serial dilutions. If phantom hCG from heterophile antibodies is at play, serial dilutions will result in a nonlinear dilution response.
If the patient’s urine hCG test is positive, then pregnancy should be ruled out with a transvaginal ultrasound. If negative, an ectopic pregnancy should still be considered (unless not medically plausible, such as in postmenopausal women or women who have undergone hysterectomy). In the absence of an intrauterine or ectopic pregnancy, a positive serum and urine pregnancy test could be from exogenous hCG, from malignancy or pituitary hCG. Use of exogenous hCG can be ruled out by taking a thorough history, with particular focus on asking about weight loss medications and muscle building therapies.
If pregnancy and exogenous hCG are ruled out, clinicians should assess for an occult hCG-secreting malignancy. The lab should be asked to measure the proportion of the free beta subunit of hCG, as this is typically what is secreted by malignancies. CT imaging of the chest, abdomen, and pelvis to search for an occult primary tumor should take place. If the patient has been recently treated for molar pregnancy or GTN, and serum hCG levels reside between 100 and 300 mIU/mL, quiescent GTD should be considered the diagnosis. Determination of the proportion of hyperglycosylated hCG to total hCG can help differentiate active choriocarcinoma from quiescent GTD. After restaging imaging has been done to confirm no measurable metastatic foci, observation can follow with monthly hCG measurements. The majority of these cases will eventually resolve without intervention within a year. Quiescent GTD and persistent low-level HCG in the absence of measurable GTN on imaging or symptoms does not require treatment with chemotherapy or hysterectomy, particularly in women who desire future fertility.2
Once occult malignancy has been ruled out, the remaining potential source of hCG is the pituitary gland. As mentioned earlier, hCG shares its morphology with TSH, LH, and FSH. This can result in cross reactivity and false positives. In the menopausal state, GnRH levels increase and thus so do pituitary LH and hCG levels. To confirm that the pituitary is the source of the low-level hCG levels, the provider should prescribe a course of hormonal treatment such as an oral contraceptive pill for a 2- to 3-month period. This should result in suppression of pituitary hCG, and serum hCG levels, as part of a negative feedback loop. Pituitary source of hCG is a benign condition, and, like quiescent GTD, phantom hCG or exogenous hCG does not require intervention.
Getting to the bottom of persistent low-level hCG elevations can be challenging. By following the step-wise algorithm listed here, clinicians can sequentially test for urine hCG, heterophilic antibodies, elevated free beta-subunit, occult malignancy, and pituitary hCG.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Email her at [email protected].
References
1. Oyatogun O et al. Ther Adv Reprod Health 2021 Jun 13. doi: 10.1177/2F26334941211016412.
2. Soper JT. Obstet Gynecol. 2021 Feb 1;137(2):355-70.
A human chorionic gonadotropin (hCG) test is commonly ordered by gynecologists prior to surgical procedures, in the workup of bleeding abnormalities, and in the follow-up of ectopic and molar pregnancies, to name a few indications. In doing so, occasionally clinicians will find themselves in the diagnostic dilemma of discovering an inexplicable low-level elevation in hCG, such as in a postmenopausal patient. This clinical picture can be confusing and can be concerning for conditions such as postmolar gestational trophoblastic neoplasia (GTN). However, there can be benign causes of this phenomenon.1 To prevent unnecessary worry, investigation of treatments is important. In fact, misdiagnosis and inappropriate treatment of benign, low-level hCG levels with unnecessary chemotherapy is problematic mismanagement of gestational trophoblastic disease (GTD), and a major cause of litigation.
Human chorionic gonadotropin is a glycoprotein hormone with two subunits (alpha and beta). It can come from multiple sources, including trophoblastic cells, malignant trophoblastic cells, the pituitary gland, and exogenous sources.1 Its alpha-subunit is identical to that of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH). Its beta-subunit is unique, though very similar to that of LH. The free hCG beta subunit can be produced by nontrophoblastic neoplasms. The gene for the beta subunit of hCG is in close proximity to the beta subunit of LH and increases in gonadotropin-releasing hormone (GnRH) in menopause can result in the stimulation of both genes. Understanding the sources of hCG-like glycoproteins and mechanisms for testing is important when considering possible causes for falsely elevated hCG.
Most commercially available serum hCG assays detect normal intact hCG and free beta subunits. They are typically sandwich assays utilizing antibody binding sites in which a solid-phase anti-hCG antibody to a specific hCG target is then mixed with the patient’s serum, trapping or binding the hCG, which is then treated with an indicator antibody. After being washed with the indicator or “capture” antibody, its relative (quantitative) levels can be measured.1
Urine hCG testing (such as urine pregnancy tests) work through capillary action, drawing the patient’s urine across absorbent pads before reaching a pad which contains anti-hCG antibodies (the detection zone) in the test line. These tests are less sensitive than serum tests, but many can detect hCG levels <15-20 mIU/mL.1
When ob.gyns. are asked to consult on or evaluate persistently low-level elevations of hCG in nonpregnant patients they should consider both malignant and nonmalignant etiologies. Malignant causes include GTN or quiescent GTD (e.g., after treatment of a molar pregnancy or GTN), choriocarcinoma (e.g., ovarian germ cell tumors), and nonchoriocarcinoma malignancies (such as cervical, pancreatic, breast, renal). Nonmalignant causes of hCG elevations in nonpregnant patients include pituitary hCG (in postmenopausal patients), exogenous hCG, and phantom hCG.
The first step in diagnostic workup is to perform a urine pregnancy test. Provided that the serum hCG level is > 20 mIU/mL, the urine HCG should be positive unless the cause of elevated levels is “phantom hCG” from heterophilic antibodies. When patients are exposed to animal antigens (such as in vaccines) they can develop antibodies such as human anti-mouse antibody. These antibodies have affinity to the binding antibodies used in many hCG sandwich assays and form a linkage between the solid phase antibody and the detection antibody creating a false-positive result. This false-positive test is only present in serum testing but not urine tests because the patient’s heterophilic antibodies are not excreted by the kidney and thus not available to create a false-positive result. An alternative method to make the diagnosis of phantom hCG is to request that the hCG testing be run at a different lab with a different assay (which may not react with the same affinity to the patient’s anti-animal heterophile antibodies), or to request that the lab perform serial dilutions. If phantom hCG from heterophile antibodies is at play, serial dilutions will result in a nonlinear dilution response.
If the patient’s urine hCG test is positive, then pregnancy should be ruled out with a transvaginal ultrasound. If negative, an ectopic pregnancy should still be considered (unless not medically plausible, such as in postmenopausal women or women who have undergone hysterectomy). In the absence of an intrauterine or ectopic pregnancy, a positive serum and urine pregnancy test could be from exogenous hCG, from malignancy or pituitary hCG. Use of exogenous hCG can be ruled out by taking a thorough history, with particular focus on asking about weight loss medications and muscle building therapies.
If pregnancy and exogenous hCG are ruled out, clinicians should assess for an occult hCG-secreting malignancy. The lab should be asked to measure the proportion of the free beta subunit of hCG, as this is typically what is secreted by malignancies. CT imaging of the chest, abdomen, and pelvis to search for an occult primary tumor should take place. If the patient has been recently treated for molar pregnancy or GTN, and serum hCG levels reside between 100 and 300 mIU/mL, quiescent GTD should be considered the diagnosis. Determination of the proportion of hyperglycosylated hCG to total hCG can help differentiate active choriocarcinoma from quiescent GTD. After restaging imaging has been done to confirm no measurable metastatic foci, observation can follow with monthly hCG measurements. The majority of these cases will eventually resolve without intervention within a year. Quiescent GTD and persistent low-level HCG in the absence of measurable GTN on imaging or symptoms does not require treatment with chemotherapy or hysterectomy, particularly in women who desire future fertility.2
Once occult malignancy has been ruled out, the remaining potential source of hCG is the pituitary gland. As mentioned earlier, hCG shares its morphology with TSH, LH, and FSH. This can result in cross reactivity and false positives. In the menopausal state, GnRH levels increase and thus so do pituitary LH and hCG levels. To confirm that the pituitary is the source of the low-level hCG levels, the provider should prescribe a course of hormonal treatment such as an oral contraceptive pill for a 2- to 3-month period. This should result in suppression of pituitary hCG, and serum hCG levels, as part of a negative feedback loop. Pituitary source of hCG is a benign condition, and, like quiescent GTD, phantom hCG or exogenous hCG does not require intervention.
Getting to the bottom of persistent low-level hCG elevations can be challenging. By following the step-wise algorithm listed here, clinicians can sequentially test for urine hCG, heterophilic antibodies, elevated free beta-subunit, occult malignancy, and pituitary hCG.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Email her at [email protected].
References
1. Oyatogun O et al. Ther Adv Reprod Health 2021 Jun 13. doi: 10.1177/2F26334941211016412.
2. Soper JT. Obstet Gynecol. 2021 Feb 1;137(2):355-70.
A human chorionic gonadotropin (hCG) test is commonly ordered by gynecologists prior to surgical procedures, in the workup of bleeding abnormalities, and in the follow-up of ectopic and molar pregnancies, to name a few indications. In doing so, occasionally clinicians will find themselves in the diagnostic dilemma of discovering an inexplicable low-level elevation in hCG, such as in a postmenopausal patient. This clinical picture can be confusing and can be concerning for conditions such as postmolar gestational trophoblastic neoplasia (GTN). However, there can be benign causes of this phenomenon.1 To prevent unnecessary worry, investigation of treatments is important. In fact, misdiagnosis and inappropriate treatment of benign, low-level hCG levels with unnecessary chemotherapy is problematic mismanagement of gestational trophoblastic disease (GTD), and a major cause of litigation.
Human chorionic gonadotropin is a glycoprotein hormone with two subunits (alpha and beta). It can come from multiple sources, including trophoblastic cells, malignant trophoblastic cells, the pituitary gland, and exogenous sources.1 Its alpha-subunit is identical to that of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH). Its beta-subunit is unique, though very similar to that of LH. The free hCG beta subunit can be produced by nontrophoblastic neoplasms. The gene for the beta subunit of hCG is in close proximity to the beta subunit of LH and increases in gonadotropin-releasing hormone (GnRH) in menopause can result in the stimulation of both genes. Understanding the sources of hCG-like glycoproteins and mechanisms for testing is important when considering possible causes for falsely elevated hCG.
Most commercially available serum hCG assays detect normal intact hCG and free beta subunits. They are typically sandwich assays utilizing antibody binding sites in which a solid-phase anti-hCG antibody to a specific hCG target is then mixed with the patient’s serum, trapping or binding the hCG, which is then treated with an indicator antibody. After being washed with the indicator or “capture” antibody, its relative (quantitative) levels can be measured.1
Urine hCG testing (such as urine pregnancy tests) work through capillary action, drawing the patient’s urine across absorbent pads before reaching a pad which contains anti-hCG antibodies (the detection zone) in the test line. These tests are less sensitive than serum tests, but many can detect hCG levels <15-20 mIU/mL.1
When ob.gyns. are asked to consult on or evaluate persistently low-level elevations of hCG in nonpregnant patients they should consider both malignant and nonmalignant etiologies. Malignant causes include GTN or quiescent GTD (e.g., after treatment of a molar pregnancy or GTN), choriocarcinoma (e.g., ovarian germ cell tumors), and nonchoriocarcinoma malignancies (such as cervical, pancreatic, breast, renal). Nonmalignant causes of hCG elevations in nonpregnant patients include pituitary hCG (in postmenopausal patients), exogenous hCG, and phantom hCG.
The first step in diagnostic workup is to perform a urine pregnancy test. Provided that the serum hCG level is > 20 mIU/mL, the urine HCG should be positive unless the cause of elevated levels is “phantom hCG” from heterophilic antibodies. When patients are exposed to animal antigens (such as in vaccines) they can develop antibodies such as human anti-mouse antibody. These antibodies have affinity to the binding antibodies used in many hCG sandwich assays and form a linkage between the solid phase antibody and the detection antibody creating a false-positive result. This false-positive test is only present in serum testing but not urine tests because the patient’s heterophilic antibodies are not excreted by the kidney and thus not available to create a false-positive result. An alternative method to make the diagnosis of phantom hCG is to request that the hCG testing be run at a different lab with a different assay (which may not react with the same affinity to the patient’s anti-animal heterophile antibodies), or to request that the lab perform serial dilutions. If phantom hCG from heterophile antibodies is at play, serial dilutions will result in a nonlinear dilution response.
If the patient’s urine hCG test is positive, then pregnancy should be ruled out with a transvaginal ultrasound. If negative, an ectopic pregnancy should still be considered (unless not medically plausible, such as in postmenopausal women or women who have undergone hysterectomy). In the absence of an intrauterine or ectopic pregnancy, a positive serum and urine pregnancy test could be from exogenous hCG, from malignancy or pituitary hCG. Use of exogenous hCG can be ruled out by taking a thorough history, with particular focus on asking about weight loss medications and muscle building therapies.
If pregnancy and exogenous hCG are ruled out, clinicians should assess for an occult hCG-secreting malignancy. The lab should be asked to measure the proportion of the free beta subunit of hCG, as this is typically what is secreted by malignancies. CT imaging of the chest, abdomen, and pelvis to search for an occult primary tumor should take place. If the patient has been recently treated for molar pregnancy or GTN, and serum hCG levels reside between 100 and 300 mIU/mL, quiescent GTD should be considered the diagnosis. Determination of the proportion of hyperglycosylated hCG to total hCG can help differentiate active choriocarcinoma from quiescent GTD. After restaging imaging has been done to confirm no measurable metastatic foci, observation can follow with monthly hCG measurements. The majority of these cases will eventually resolve without intervention within a year. Quiescent GTD and persistent low-level HCG in the absence of measurable GTN on imaging or symptoms does not require treatment with chemotherapy or hysterectomy, particularly in women who desire future fertility.2
Once occult malignancy has been ruled out, the remaining potential source of hCG is the pituitary gland. As mentioned earlier, hCG shares its morphology with TSH, LH, and FSH. This can result in cross reactivity and false positives. In the menopausal state, GnRH levels increase and thus so do pituitary LH and hCG levels. To confirm that the pituitary is the source of the low-level hCG levels, the provider should prescribe a course of hormonal treatment such as an oral contraceptive pill for a 2- to 3-month period. This should result in suppression of pituitary hCG, and serum hCG levels, as part of a negative feedback loop. Pituitary source of hCG is a benign condition, and, like quiescent GTD, phantom hCG or exogenous hCG does not require intervention.
Getting to the bottom of persistent low-level hCG elevations can be challenging. By following the step-wise algorithm listed here, clinicians can sequentially test for urine hCG, heterophilic antibodies, elevated free beta-subunit, occult malignancy, and pituitary hCG.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Email her at [email protected].
References
1. Oyatogun O et al. Ther Adv Reprod Health 2021 Jun 13. doi: 10.1177/2F26334941211016412.
2. Soper JT. Obstet Gynecol. 2021 Feb 1;137(2):355-70.
The male biological clock – How to tell the time
For decades, we have recognized the age-related natural decline in female fecundity (the ability to reproduce) after the age of 30 (Maturitas 1988;[Suppl]1:15-22). Advanced maternal age (AMA) has also been demonstrated to increase miscarriage and pregnancies with chromosomal abnormalities, presumably from the increased rate of oocyte aneuploidy. There has been a sixfold increase in the rate of first birth in women aged 35-39 years (NCHS Data Brief 2014;152:1-8). Consequently, over the last decade, women, often before they reach AMA, have turned to elective oocyte cryopreservation for fertility preservation.
Ovarian aging
Ovarian aging occurs through the decline in quality and quantity of oocytes. The former is a reflection of the woman’s chronologic age. Markers of female ovarian aging have been utilized, for the past 3 decades, most commonly by basal follicle stimulating hormone. Currently, to assess the quantity of ovarian follicles, antimüllerian hormone (AMH) and transvaginal ultrasound for ovarian antral follicle count (AFC) are the most accurate indicators (J Clin Endocrinol Metab 2004:89:2977-81). While ovarian age testing, particularly AMH, has been widely used to assess a woman’s “fertility potential,” it does not reflect her natural fecundity. In a prospective cohort study, AMH levels (ng/mL) divided into < 0.7, 0.7-8.4, and > 8.4, did not affect natural conception in women aged 30-44 who were divided into the categories of <35, 35-37, or 38-44 years (JAMA 2017;318:1367-76). Although AMH does reduce success with IVF, its main value is the inverse correlation when prescribing gonadotropin dosage for controlled ovarian stimulation.
Despite the familiarity with ovarian aging effects on fertility, the male biological clock remains less studied and understood. Over the last 4 decades, paternal age has increased an average of 3.5 years presumably due to delayed child rearing from professional or personal reasons, improved contraception as well as increased divorce, remarriage, and life expectancy (Hum Reprod. 2017;32:2110-6). Nevertheless, we have little data to definitively counsel men on the effects of advanced paternal age (APA) and no consensus on an actual defined age of designation. This month’s article will summarize the current literature on male age and its impact on fertility.
Testicular aging
Men older than 45 years require approximately five times longer to achieve a pregnancy as men less than 25 after adjustment for female age (Fertil Steril. 2003;79:1520-7). The most likely parameter to assess male fertility, other than pregnancy rates, would be the sperm. Sperm counts, beginning at age 41, may decline but concentrations have been shown to increase in older men apparently because of declining semen volume (Ageing Res Rev. 2015;19:22-33). Sperm motility, but not morphology, also declines while genetic alterations of sperm increase with age. The issue of chromosomal abnormalities in sperm from men of advanced age appears to be similar to that in the oocytes of women with AMA. Consequently, both sexes may contribute to embryo aneuploidy resulting in declining fertility and increasing miscarriage.
For all ages, studies have suggested that elevated male body mass index as well as alcohol consumption and cigarette smoking, including e-cigarettes, can lead to impaired sperm production (Hum Reprod Update 2013;19:221-31).
Fertility treatment outcomes
A mainstay of fertility treatment, particularly in men with mild to moderate impairments in semen parameters, is ovulation induction with intrauterine insemination. Male age has been shown to be a significant indicator for pregnancy rates, including those with normal semen parameters (J Obstet Gynaecol. 2011;31:420-3). Men above age 45 contributed to lower pregnancy rates and higher miscarriages during IUI treatment cycles (Reprod BioMed Online 2008;17:392-7).
During IVF cycles, the sperm of men with APA often undergo ICSI (intracytoplasmic sperm injection) due to higher fertilization rates compared with standard insemination. However, APA sperm appear to have lower fertilization rates and decreased embryo development to the blastocyst stage during cycles using donor oocytes, although pregnancy outcomes are inconsistent (Trans Androl Urol. 2019;8[Suppl 1]:S22-S30; Fertil Steril. 2008;90:97-103).
Perinatal and children’s health
The offspring from APA men appear to have higher rates of stillbirth, low birth weight, and preterm birth, as well as birth defects. Men older than 40-45 years have twice the risk of an autistic child and three times the risk of schizophrenia in their offspring (Transl Psychiatry 2017;7:e1019; Am J Psychiatry 2002;159:1528-33).
Conclusions
Most of the literature supports negative effects on sperm and reproduction from men with APA. The challenge in deciphering the true role of APA on fertility is that the partner is often of AMA. A consideration to avoid this effect would be sperm cryopreservation at a younger age, similar to the common trend among women. Preimplantation genetic testing of embryos from men with APA is also a potential option to reduce miscarriage and avoid a chromosomally abnormal pregnancy. Ethicists have pondered the impact of APA on parenthood and the detrimental effect of early paternal death on the child. Nevertheless, the effect of APA in reproduction is a vital area to study with the same fervor as AMA (Fertil Steril 2009;92:1772-5).
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts. Email him at [email protected].
For decades, we have recognized the age-related natural decline in female fecundity (the ability to reproduce) after the age of 30 (Maturitas 1988;[Suppl]1:15-22). Advanced maternal age (AMA) has also been demonstrated to increase miscarriage and pregnancies with chromosomal abnormalities, presumably from the increased rate of oocyte aneuploidy. There has been a sixfold increase in the rate of first birth in women aged 35-39 years (NCHS Data Brief 2014;152:1-8). Consequently, over the last decade, women, often before they reach AMA, have turned to elective oocyte cryopreservation for fertility preservation.
Ovarian aging
Ovarian aging occurs through the decline in quality and quantity of oocytes. The former is a reflection of the woman’s chronologic age. Markers of female ovarian aging have been utilized, for the past 3 decades, most commonly by basal follicle stimulating hormone. Currently, to assess the quantity of ovarian follicles, antimüllerian hormone (AMH) and transvaginal ultrasound for ovarian antral follicle count (AFC) are the most accurate indicators (J Clin Endocrinol Metab 2004:89:2977-81). While ovarian age testing, particularly AMH, has been widely used to assess a woman’s “fertility potential,” it does not reflect her natural fecundity. In a prospective cohort study, AMH levels (ng/mL) divided into < 0.7, 0.7-8.4, and > 8.4, did not affect natural conception in women aged 30-44 who were divided into the categories of <35, 35-37, or 38-44 years (JAMA 2017;318:1367-76). Although AMH does reduce success with IVF, its main value is the inverse correlation when prescribing gonadotropin dosage for controlled ovarian stimulation.
Despite the familiarity with ovarian aging effects on fertility, the male biological clock remains less studied and understood. Over the last 4 decades, paternal age has increased an average of 3.5 years presumably due to delayed child rearing from professional or personal reasons, improved contraception as well as increased divorce, remarriage, and life expectancy (Hum Reprod. 2017;32:2110-6). Nevertheless, we have little data to definitively counsel men on the effects of advanced paternal age (APA) and no consensus on an actual defined age of designation. This month’s article will summarize the current literature on male age and its impact on fertility.
Testicular aging
Men older than 45 years require approximately five times longer to achieve a pregnancy as men less than 25 after adjustment for female age (Fertil Steril. 2003;79:1520-7). The most likely parameter to assess male fertility, other than pregnancy rates, would be the sperm. Sperm counts, beginning at age 41, may decline but concentrations have been shown to increase in older men apparently because of declining semen volume (Ageing Res Rev. 2015;19:22-33). Sperm motility, but not morphology, also declines while genetic alterations of sperm increase with age. The issue of chromosomal abnormalities in sperm from men of advanced age appears to be similar to that in the oocytes of women with AMA. Consequently, both sexes may contribute to embryo aneuploidy resulting in declining fertility and increasing miscarriage.
For all ages, studies have suggested that elevated male body mass index as well as alcohol consumption and cigarette smoking, including e-cigarettes, can lead to impaired sperm production (Hum Reprod Update 2013;19:221-31).
Fertility treatment outcomes
A mainstay of fertility treatment, particularly in men with mild to moderate impairments in semen parameters, is ovulation induction with intrauterine insemination. Male age has been shown to be a significant indicator for pregnancy rates, including those with normal semen parameters (J Obstet Gynaecol. 2011;31:420-3). Men above age 45 contributed to lower pregnancy rates and higher miscarriages during IUI treatment cycles (Reprod BioMed Online 2008;17:392-7).
During IVF cycles, the sperm of men with APA often undergo ICSI (intracytoplasmic sperm injection) due to higher fertilization rates compared with standard insemination. However, APA sperm appear to have lower fertilization rates and decreased embryo development to the blastocyst stage during cycles using donor oocytes, although pregnancy outcomes are inconsistent (Trans Androl Urol. 2019;8[Suppl 1]:S22-S30; Fertil Steril. 2008;90:97-103).
Perinatal and children’s health
The offspring from APA men appear to have higher rates of stillbirth, low birth weight, and preterm birth, as well as birth defects. Men older than 40-45 years have twice the risk of an autistic child and three times the risk of schizophrenia in their offspring (Transl Psychiatry 2017;7:e1019; Am J Psychiatry 2002;159:1528-33).
Conclusions
Most of the literature supports negative effects on sperm and reproduction from men with APA. The challenge in deciphering the true role of APA on fertility is that the partner is often of AMA. A consideration to avoid this effect would be sperm cryopreservation at a younger age, similar to the common trend among women. Preimplantation genetic testing of embryos from men with APA is also a potential option to reduce miscarriage and avoid a chromosomally abnormal pregnancy. Ethicists have pondered the impact of APA on parenthood and the detrimental effect of early paternal death on the child. Nevertheless, the effect of APA in reproduction is a vital area to study with the same fervor as AMA (Fertil Steril 2009;92:1772-5).
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts. Email him at [email protected].
For decades, we have recognized the age-related natural decline in female fecundity (the ability to reproduce) after the age of 30 (Maturitas 1988;[Suppl]1:15-22). Advanced maternal age (AMA) has also been demonstrated to increase miscarriage and pregnancies with chromosomal abnormalities, presumably from the increased rate of oocyte aneuploidy. There has been a sixfold increase in the rate of first birth in women aged 35-39 years (NCHS Data Brief 2014;152:1-8). Consequently, over the last decade, women, often before they reach AMA, have turned to elective oocyte cryopreservation for fertility preservation.
Ovarian aging
Ovarian aging occurs through the decline in quality and quantity of oocytes. The former is a reflection of the woman’s chronologic age. Markers of female ovarian aging have been utilized, for the past 3 decades, most commonly by basal follicle stimulating hormone. Currently, to assess the quantity of ovarian follicles, antimüllerian hormone (AMH) and transvaginal ultrasound for ovarian antral follicle count (AFC) are the most accurate indicators (J Clin Endocrinol Metab 2004:89:2977-81). While ovarian age testing, particularly AMH, has been widely used to assess a woman’s “fertility potential,” it does not reflect her natural fecundity. In a prospective cohort study, AMH levels (ng/mL) divided into < 0.7, 0.7-8.4, and > 8.4, did not affect natural conception in women aged 30-44 who were divided into the categories of <35, 35-37, or 38-44 years (JAMA 2017;318:1367-76). Although AMH does reduce success with IVF, its main value is the inverse correlation when prescribing gonadotropin dosage for controlled ovarian stimulation.
Despite the familiarity with ovarian aging effects on fertility, the male biological clock remains less studied and understood. Over the last 4 decades, paternal age has increased an average of 3.5 years presumably due to delayed child rearing from professional or personal reasons, improved contraception as well as increased divorce, remarriage, and life expectancy (Hum Reprod. 2017;32:2110-6). Nevertheless, we have little data to definitively counsel men on the effects of advanced paternal age (APA) and no consensus on an actual defined age of designation. This month’s article will summarize the current literature on male age and its impact on fertility.
Testicular aging
Men older than 45 years require approximately five times longer to achieve a pregnancy as men less than 25 after adjustment for female age (Fertil Steril. 2003;79:1520-7). The most likely parameter to assess male fertility, other than pregnancy rates, would be the sperm. Sperm counts, beginning at age 41, may decline but concentrations have been shown to increase in older men apparently because of declining semen volume (Ageing Res Rev. 2015;19:22-33). Sperm motility, but not morphology, also declines while genetic alterations of sperm increase with age. The issue of chromosomal abnormalities in sperm from men of advanced age appears to be similar to that in the oocytes of women with AMA. Consequently, both sexes may contribute to embryo aneuploidy resulting in declining fertility and increasing miscarriage.
For all ages, studies have suggested that elevated male body mass index as well as alcohol consumption and cigarette smoking, including e-cigarettes, can lead to impaired sperm production (Hum Reprod Update 2013;19:221-31).
Fertility treatment outcomes
A mainstay of fertility treatment, particularly in men with mild to moderate impairments in semen parameters, is ovulation induction with intrauterine insemination. Male age has been shown to be a significant indicator for pregnancy rates, including those with normal semen parameters (J Obstet Gynaecol. 2011;31:420-3). Men above age 45 contributed to lower pregnancy rates and higher miscarriages during IUI treatment cycles (Reprod BioMed Online 2008;17:392-7).
During IVF cycles, the sperm of men with APA often undergo ICSI (intracytoplasmic sperm injection) due to higher fertilization rates compared with standard insemination. However, APA sperm appear to have lower fertilization rates and decreased embryo development to the blastocyst stage during cycles using donor oocytes, although pregnancy outcomes are inconsistent (Trans Androl Urol. 2019;8[Suppl 1]:S22-S30; Fertil Steril. 2008;90:97-103).
Perinatal and children’s health
The offspring from APA men appear to have higher rates of stillbirth, low birth weight, and preterm birth, as well as birth defects. Men older than 40-45 years have twice the risk of an autistic child and three times the risk of schizophrenia in their offspring (Transl Psychiatry 2017;7:e1019; Am J Psychiatry 2002;159:1528-33).
Conclusions
Most of the literature supports negative effects on sperm and reproduction from men with APA. The challenge in deciphering the true role of APA on fertility is that the partner is often of AMA. A consideration to avoid this effect would be sperm cryopreservation at a younger age, similar to the common trend among women. Preimplantation genetic testing of embryos from men with APA is also a potential option to reduce miscarriage and avoid a chromosomally abnormal pregnancy. Ethicists have pondered the impact of APA on parenthood and the detrimental effect of early paternal death on the child. Nevertheless, the effect of APA in reproduction is a vital area to study with the same fervor as AMA (Fertil Steril 2009;92:1772-5).
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts. Email him at [email protected].
Low androgen in kidney recipients tied to diabetes
Low androgen levels appear to be linked to the development of posttransplantation diabetes mellitus (PTDM) in male kidney transplant recipients, new research suggests.
Among 243 men who did not have diabetes prior to undergoing kidney transplantation, levels of both dihydrotestosterone (DHT) and testosterone were inversely related to the risk for developing diabetes the next 5 years.
“These results suggest that androgen insufficiency could play a role in the frequent deterioration of the glucose metabolism after kidney transplantation,” Suzanne P. Stam and colleagues wrote in Diabetes Care.
However, “our study has unfortunately no direct clinical findings as it was of an observational nature,” Ms. Stam told this news organization. “As a result, we can say that we have observed an association and have not established a causal relationship. So based on our study alone there is not a reason to start screening for low androgen values.”
Previous data have suggested that failure of pancreatic beta cell secretion of insulin plays a role in PTDM. In addition, DHT appears to act on the androgen receptor in pancreatic beta cells to enhance insulin secretion, while testosterone deficiency has been shown to play a role in the development of type 2 diabetes in aging males and in men receiving androgen-deprivation therapy. And, randomized clinical trials have found favorable metabolic effects of testosterone replacement therapy in hypogonadal men with type 2 diabetes.
The current post hoc analysis of a prospective single-center cohort study is the first longitudinal epidemiological investigation of the role of androgens in PTDM in kidney transplant recipients. The subjects, all men, had functioning grafts for at least a year posttransplantation. Androgen levels were assessed by liquid chromatography–tandem mass spectrometry.
At a median follow-up duration of 5.3 years, 28 (11.5%) of the men had developed PTDM. By DHT tertile, the proportions developing diabetes were 19% (15) for the lowest, 12% (10) for the middle, and 4% (3) for men with the highest DHT tertile (P = .008). A similar relationship was seen with tertiles of testosterone, with 17% (14), 14% (11), and 4% (3) developing diabetes in the lowest, middle, and highest tertiles, respectively (P = .01).
In unadjusted analysis, every doubling of DHT was linked to a 27% increased risk for PTDM (P < .001). The association remained significant after adjustments for age, estimated glomerular filtration rate, time between transplantation and baseline, body mass index, high sensitivity C-reactive protein, medication use, and baseline hemoglobin A1c (all P < .001). Similar results were found with total testosterone.
Ms. Stam, of the division of nephrology at the University Medical Center Groningen, the Netherlands, noted in an interview that, in the Netherlands, about 15% of those with kidney failure have preexisting diabetes, compared with about 50% in other western countries, including the United States.
She said that her team is currently working on a study to investigate the association between androgens and the development of PTDM in female kidney transplant recipients.
The study was funded by the TransplantLines Food and Nutrition Biobank and Cohort Study, Top Institute Food and Nutrition, and partly by the European Union’s Horizon 2020 research and innovation program. Ms. Stam and the other authors have no further disclosures.
Low androgen levels appear to be linked to the development of posttransplantation diabetes mellitus (PTDM) in male kidney transplant recipients, new research suggests.
Among 243 men who did not have diabetes prior to undergoing kidney transplantation, levels of both dihydrotestosterone (DHT) and testosterone were inversely related to the risk for developing diabetes the next 5 years.
“These results suggest that androgen insufficiency could play a role in the frequent deterioration of the glucose metabolism after kidney transplantation,” Suzanne P. Stam and colleagues wrote in Diabetes Care.
However, “our study has unfortunately no direct clinical findings as it was of an observational nature,” Ms. Stam told this news organization. “As a result, we can say that we have observed an association and have not established a causal relationship. So based on our study alone there is not a reason to start screening for low androgen values.”
Previous data have suggested that failure of pancreatic beta cell secretion of insulin plays a role in PTDM. In addition, DHT appears to act on the androgen receptor in pancreatic beta cells to enhance insulin secretion, while testosterone deficiency has been shown to play a role in the development of type 2 diabetes in aging males and in men receiving androgen-deprivation therapy. And, randomized clinical trials have found favorable metabolic effects of testosterone replacement therapy in hypogonadal men with type 2 diabetes.
The current post hoc analysis of a prospective single-center cohort study is the first longitudinal epidemiological investigation of the role of androgens in PTDM in kidney transplant recipients. The subjects, all men, had functioning grafts for at least a year posttransplantation. Androgen levels were assessed by liquid chromatography–tandem mass spectrometry.
At a median follow-up duration of 5.3 years, 28 (11.5%) of the men had developed PTDM. By DHT tertile, the proportions developing diabetes were 19% (15) for the lowest, 12% (10) for the middle, and 4% (3) for men with the highest DHT tertile (P = .008). A similar relationship was seen with tertiles of testosterone, with 17% (14), 14% (11), and 4% (3) developing diabetes in the lowest, middle, and highest tertiles, respectively (P = .01).
In unadjusted analysis, every doubling of DHT was linked to a 27% increased risk for PTDM (P < .001). The association remained significant after adjustments for age, estimated glomerular filtration rate, time between transplantation and baseline, body mass index, high sensitivity C-reactive protein, medication use, and baseline hemoglobin A1c (all P < .001). Similar results were found with total testosterone.
Ms. Stam, of the division of nephrology at the University Medical Center Groningen, the Netherlands, noted in an interview that, in the Netherlands, about 15% of those with kidney failure have preexisting diabetes, compared with about 50% in other western countries, including the United States.
She said that her team is currently working on a study to investigate the association between androgens and the development of PTDM in female kidney transplant recipients.
The study was funded by the TransplantLines Food and Nutrition Biobank and Cohort Study, Top Institute Food and Nutrition, and partly by the European Union’s Horizon 2020 research and innovation program. Ms. Stam and the other authors have no further disclosures.
Low androgen levels appear to be linked to the development of posttransplantation diabetes mellitus (PTDM) in male kidney transplant recipients, new research suggests.
Among 243 men who did not have diabetes prior to undergoing kidney transplantation, levels of both dihydrotestosterone (DHT) and testosterone were inversely related to the risk for developing diabetes the next 5 years.
“These results suggest that androgen insufficiency could play a role in the frequent deterioration of the glucose metabolism after kidney transplantation,” Suzanne P. Stam and colleagues wrote in Diabetes Care.
However, “our study has unfortunately no direct clinical findings as it was of an observational nature,” Ms. Stam told this news organization. “As a result, we can say that we have observed an association and have not established a causal relationship. So based on our study alone there is not a reason to start screening for low androgen values.”
Previous data have suggested that failure of pancreatic beta cell secretion of insulin plays a role in PTDM. In addition, DHT appears to act on the androgen receptor in pancreatic beta cells to enhance insulin secretion, while testosterone deficiency has been shown to play a role in the development of type 2 diabetes in aging males and in men receiving androgen-deprivation therapy. And, randomized clinical trials have found favorable metabolic effects of testosterone replacement therapy in hypogonadal men with type 2 diabetes.
The current post hoc analysis of a prospective single-center cohort study is the first longitudinal epidemiological investigation of the role of androgens in PTDM in kidney transplant recipients. The subjects, all men, had functioning grafts for at least a year posttransplantation. Androgen levels were assessed by liquid chromatography–tandem mass spectrometry.
At a median follow-up duration of 5.3 years, 28 (11.5%) of the men had developed PTDM. By DHT tertile, the proportions developing diabetes were 19% (15) for the lowest, 12% (10) for the middle, and 4% (3) for men with the highest DHT tertile (P = .008). A similar relationship was seen with tertiles of testosterone, with 17% (14), 14% (11), and 4% (3) developing diabetes in the lowest, middle, and highest tertiles, respectively (P = .01).
In unadjusted analysis, every doubling of DHT was linked to a 27% increased risk for PTDM (P < .001). The association remained significant after adjustments for age, estimated glomerular filtration rate, time between transplantation and baseline, body mass index, high sensitivity C-reactive protein, medication use, and baseline hemoglobin A1c (all P < .001). Similar results were found with total testosterone.
Ms. Stam, of the division of nephrology at the University Medical Center Groningen, the Netherlands, noted in an interview that, in the Netherlands, about 15% of those with kidney failure have preexisting diabetes, compared with about 50% in other western countries, including the United States.
She said that her team is currently working on a study to investigate the association between androgens and the development of PTDM in female kidney transplant recipients.
The study was funded by the TransplantLines Food and Nutrition Biobank and Cohort Study, Top Institute Food and Nutrition, and partly by the European Union’s Horizon 2020 research and innovation program. Ms. Stam and the other authors have no further disclosures.
FROM DIABETES CARE
COVID-19 pandemic affects menstrual cycles, presenting challenges for conception
A survey of more than 12,000 women of reproductive age found that one in three had experienced changes to their menstrual cycles and symptoms during the COVID-19 pandemic. Noticeably higher stress levels than prepandemic benchmarks could be affecting menstruation.
This has implications for women trying to conceive or struggling with infertility, said Shannon M. Malloy, a research and data associate with Ovia Health, a women’s and family health technology company in Boston. Ms. Malloy presented this study at the American Society of Reproductive Medicine’s 2021 meeting.
COVID-19 has introduced new psychosocial, interpersonal, and environmental stressors. The pandemic is “one of the most stressful, collectively experienced disasters modern society has ever seen,” said Ms. Malloy. Once imagined as an explicit event in time, COVID-19 has ingrained itself into daily life for the foreseeable future.
Research has shown that chronic, long-term stress produces high cortisol levels, which can alter endocrinology and regulation of menstrual cycles. This can make family building even more challenging, said Ms. Malloy. Physicians and other providers have always taken stress into account when managing patients, but never at this level of chronic, episodic stress, she said.
Survey examines impact on ART
Ovia Health decided to investigate the relationship between perceived stress and menstrual cycle and symptom changes during the COVID-19 pandemic, to see how it might affect assisted reproductive technology (ART).
From March 2020 to April 2021, users of Ovia Health’s Fertility mobile application in the United States took part in a survey. Items captured changes in menstruation pattern and symptomatology and included the Perceived Stress Scale 4-item version (PSS-4). A paired t-test evaluated differences between groups (menstrual changes versus no menstrual changes). The survey asked participants what changes they noticed in their menstrual cycle and why they thought cycle patterns or symptoms changed.
One-third report changes in cycle, symptoms
Among 12,302 respondents, 1 in 3 (36%) reported changes in cycle or symptoms. Eighty-seven percent said that their cycle started early or late. Twenty-nine percent reported stronger symptoms during menstruation such as low back pain, cramping, or discharge changes, and 27% said bleeding was heavier during periods.
These results are similar to other studies investigating the affect of episodic stress on menstruation, said Ms. Malloy.
Those who reported menstrual cycle or symptom changes scored higher on average on the PSS-4 compared with those who didn’t report any changes (8.5 v. 8.3, respectively, P < .05). PSS-4 scores across the board were notably higher in all respondents, regardless of cycle/symptom irregularity, compared with prepandemic benchmarking in similar populations.
Slightly more than half (55%) thought stress contributed to their menstrual cycle pattern and/or symptom changes, whereas 33% pointed to changes in mental health, such as depression or anxiety. “Interestingly, many users believed the COVID-19 vaccine impacted their menstrual cycle symptom changes,” said Ms. Malloy.
No definitive link between vaccine, menstruation
While known side effects of the vaccine include sore arm, fever, fatigue, and myalgia, some women have reported changes in their menstrual cycle, Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida and director of the IVF Center in Orlando, said in an interview.
“Vaccination reaction from the immune response rather than the vaccine may be the implicating factor,” said Dr. Trolice, who was not involved in the study.
Currently, there’s no direct link between the vaccine and subsequent effects on menstruation, he continued. “Most women experience resumption of normal intervals 1 month following vaccination. Further, there is no credible evidence that links the vaccine to infertility.
“Nevertheless, research in this area is vital and underway,” he added.
Physicians can help with stress
Menstrual cycle disruption is especially frustrating for women trying to build a family, said Ms. Malloy. Providers may be observing more menstrual irregularity in their patient populations, and seeing more patients struggle to conceive on their own, turning to ART.
Providers can’t make COVID-19 go away, but they could help patients by doing a better job of integrating mental health screening, connecting patients to treatments that optimize conception and fertility treatment outcomes, said Ms. Malloy.
The survey was limited in that its questions didn’t consider proper diagnostic criteria for irregularity, versus self-reported changes. But it does highlight the need for more research on the pandemic’s affect on menstruation and the vaccine on menstruation, said Ms. Malloy. “The National Institutes of Health in August committed $1.6 million to explore this connection. We’re looking forward to seeing what their results are.”
Dr. Trolice and Ms. Malloy had no disclosures.
A survey of more than 12,000 women of reproductive age found that one in three had experienced changes to their menstrual cycles and symptoms during the COVID-19 pandemic. Noticeably higher stress levels than prepandemic benchmarks could be affecting menstruation.
This has implications for women trying to conceive or struggling with infertility, said Shannon M. Malloy, a research and data associate with Ovia Health, a women’s and family health technology company in Boston. Ms. Malloy presented this study at the American Society of Reproductive Medicine’s 2021 meeting.
COVID-19 has introduced new psychosocial, interpersonal, and environmental stressors. The pandemic is “one of the most stressful, collectively experienced disasters modern society has ever seen,” said Ms. Malloy. Once imagined as an explicit event in time, COVID-19 has ingrained itself into daily life for the foreseeable future.
Research has shown that chronic, long-term stress produces high cortisol levels, which can alter endocrinology and regulation of menstrual cycles. This can make family building even more challenging, said Ms. Malloy. Physicians and other providers have always taken stress into account when managing patients, but never at this level of chronic, episodic stress, she said.
Survey examines impact on ART
Ovia Health decided to investigate the relationship between perceived stress and menstrual cycle and symptom changes during the COVID-19 pandemic, to see how it might affect assisted reproductive technology (ART).
From March 2020 to April 2021, users of Ovia Health’s Fertility mobile application in the United States took part in a survey. Items captured changes in menstruation pattern and symptomatology and included the Perceived Stress Scale 4-item version (PSS-4). A paired t-test evaluated differences between groups (menstrual changes versus no menstrual changes). The survey asked participants what changes they noticed in their menstrual cycle and why they thought cycle patterns or symptoms changed.
One-third report changes in cycle, symptoms
Among 12,302 respondents, 1 in 3 (36%) reported changes in cycle or symptoms. Eighty-seven percent said that their cycle started early or late. Twenty-nine percent reported stronger symptoms during menstruation such as low back pain, cramping, or discharge changes, and 27% said bleeding was heavier during periods.
These results are similar to other studies investigating the affect of episodic stress on menstruation, said Ms. Malloy.
Those who reported menstrual cycle or symptom changes scored higher on average on the PSS-4 compared with those who didn’t report any changes (8.5 v. 8.3, respectively, P < .05). PSS-4 scores across the board were notably higher in all respondents, regardless of cycle/symptom irregularity, compared with prepandemic benchmarking in similar populations.
Slightly more than half (55%) thought stress contributed to their menstrual cycle pattern and/or symptom changes, whereas 33% pointed to changes in mental health, such as depression or anxiety. “Interestingly, many users believed the COVID-19 vaccine impacted their menstrual cycle symptom changes,” said Ms. Malloy.
No definitive link between vaccine, menstruation
While known side effects of the vaccine include sore arm, fever, fatigue, and myalgia, some women have reported changes in their menstrual cycle, Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida and director of the IVF Center in Orlando, said in an interview.
“Vaccination reaction from the immune response rather than the vaccine may be the implicating factor,” said Dr. Trolice, who was not involved in the study.
Currently, there’s no direct link between the vaccine and subsequent effects on menstruation, he continued. “Most women experience resumption of normal intervals 1 month following vaccination. Further, there is no credible evidence that links the vaccine to infertility.
“Nevertheless, research in this area is vital and underway,” he added.
Physicians can help with stress
Menstrual cycle disruption is especially frustrating for women trying to build a family, said Ms. Malloy. Providers may be observing more menstrual irregularity in their patient populations, and seeing more patients struggle to conceive on their own, turning to ART.
Providers can’t make COVID-19 go away, but they could help patients by doing a better job of integrating mental health screening, connecting patients to treatments that optimize conception and fertility treatment outcomes, said Ms. Malloy.
The survey was limited in that its questions didn’t consider proper diagnostic criteria for irregularity, versus self-reported changes. But it does highlight the need for more research on the pandemic’s affect on menstruation and the vaccine on menstruation, said Ms. Malloy. “The National Institutes of Health in August committed $1.6 million to explore this connection. We’re looking forward to seeing what their results are.”
Dr. Trolice and Ms. Malloy had no disclosures.
A survey of more than 12,000 women of reproductive age found that one in three had experienced changes to their menstrual cycles and symptoms during the COVID-19 pandemic. Noticeably higher stress levels than prepandemic benchmarks could be affecting menstruation.
This has implications for women trying to conceive or struggling with infertility, said Shannon M. Malloy, a research and data associate with Ovia Health, a women’s and family health technology company in Boston. Ms. Malloy presented this study at the American Society of Reproductive Medicine’s 2021 meeting.
COVID-19 has introduced new psychosocial, interpersonal, and environmental stressors. The pandemic is “one of the most stressful, collectively experienced disasters modern society has ever seen,” said Ms. Malloy. Once imagined as an explicit event in time, COVID-19 has ingrained itself into daily life for the foreseeable future.
Research has shown that chronic, long-term stress produces high cortisol levels, which can alter endocrinology and regulation of menstrual cycles. This can make family building even more challenging, said Ms. Malloy. Physicians and other providers have always taken stress into account when managing patients, but never at this level of chronic, episodic stress, she said.
Survey examines impact on ART
Ovia Health decided to investigate the relationship between perceived stress and menstrual cycle and symptom changes during the COVID-19 pandemic, to see how it might affect assisted reproductive technology (ART).
From March 2020 to April 2021, users of Ovia Health’s Fertility mobile application in the United States took part in a survey. Items captured changes in menstruation pattern and symptomatology and included the Perceived Stress Scale 4-item version (PSS-4). A paired t-test evaluated differences between groups (menstrual changes versus no menstrual changes). The survey asked participants what changes they noticed in their menstrual cycle and why they thought cycle patterns or symptoms changed.
One-third report changes in cycle, symptoms
Among 12,302 respondents, 1 in 3 (36%) reported changes in cycle or symptoms. Eighty-seven percent said that their cycle started early or late. Twenty-nine percent reported stronger symptoms during menstruation such as low back pain, cramping, or discharge changes, and 27% said bleeding was heavier during periods.
These results are similar to other studies investigating the affect of episodic stress on menstruation, said Ms. Malloy.
Those who reported menstrual cycle or symptom changes scored higher on average on the PSS-4 compared with those who didn’t report any changes (8.5 v. 8.3, respectively, P < .05). PSS-4 scores across the board were notably higher in all respondents, regardless of cycle/symptom irregularity, compared with prepandemic benchmarking in similar populations.
Slightly more than half (55%) thought stress contributed to their menstrual cycle pattern and/or symptom changes, whereas 33% pointed to changes in mental health, such as depression or anxiety. “Interestingly, many users believed the COVID-19 vaccine impacted their menstrual cycle symptom changes,” said Ms. Malloy.
No definitive link between vaccine, menstruation
While known side effects of the vaccine include sore arm, fever, fatigue, and myalgia, some women have reported changes in their menstrual cycle, Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida and director of the IVF Center in Orlando, said in an interview.
“Vaccination reaction from the immune response rather than the vaccine may be the implicating factor,” said Dr. Trolice, who was not involved in the study.
Currently, there’s no direct link between the vaccine and subsequent effects on menstruation, he continued. “Most women experience resumption of normal intervals 1 month following vaccination. Further, there is no credible evidence that links the vaccine to infertility.
“Nevertheless, research in this area is vital and underway,” he added.
Physicians can help with stress
Menstrual cycle disruption is especially frustrating for women trying to build a family, said Ms. Malloy. Providers may be observing more menstrual irregularity in their patient populations, and seeing more patients struggle to conceive on their own, turning to ART.
Providers can’t make COVID-19 go away, but they could help patients by doing a better job of integrating mental health screening, connecting patients to treatments that optimize conception and fertility treatment outcomes, said Ms. Malloy.
The survey was limited in that its questions didn’t consider proper diagnostic criteria for irregularity, versus self-reported changes. But it does highlight the need for more research on the pandemic’s affect on menstruation and the vaccine on menstruation, said Ms. Malloy. “The National Institutes of Health in August committed $1.6 million to explore this connection. We’re looking forward to seeing what their results are.”
Dr. Trolice and Ms. Malloy had no disclosures.
FROM ASRM 2021
Patients seeking infertility care report infrequent counseling on weight loss
Physicians could be doing a better job of counseling patients with obesity and overweight on weight loss and fertility. A study of 48 women seeking infertility care at a large academic center found that less than half received advice on weight loss from their primary ob.gyn. prior to referral for infertility treatment.
Patients are thinking about this – many attempt to lose weight independently of support from their health care providers, said lead study author Margaret R. O’Neill, MD, a resident at the University of Massachusetts Medical Center in Worcester. Dr. O’Neill discussed these results at the American Society of Reproductive Medicine’s 2021 meeting.
Nearly half of all U.S. women of reproductive age have overweight or obesity, with a body mass index of >25 kg/m2. Menstrual irregularity, ovulatory dysfunction, reduced fecundity, and lower efficacy of infertility treatment are some of the consequences of obesity on fertility, said Dr. O’Neill. Obesity also affects the health of expectant mothers and fetuses, increasing the likelihood of gestational diabetes, preterm delivery, and preeclampsia, and increased incidence of fetal anomalies.
“Unfortunately, even though the prevalence of obesity has been increasing substantially in our country, there’s not excellent rates of this being addressed by physicians,” said Dr. O’Neill. BMI is often left out of documentation and rates of referrals to weight loss specialists are also low.
Conversations have been taking place about IVF centers instituting different BMI cutoffs for certain types of assisted reproductive technology, she noted.
Dr. O’Neill and her colleagues undertook a survey to see what advice community providers were dispensing about weight management on fertility.
Infertility specialists offer the most guidance
The prospective study included 48 nonpregnant women of reproductive age women presenting for IVF who needed an anesthesia consultation because of elevated BMI (> 35) prior to initiation of IVF. Mean age was 36 years and mean BMI was 38.5. More than 70% of the patients were White and they were predominantly English speakers.
All participants had attempted weight loss, including an attempt in the last year, and 93.8% reported trying to lose weight in the last year. On average, patients weighed about 20 pounds less than their heaviest adult weight. Nineteen percent of the participants were at their heaviest adult weight.
While 60% said they’d received weight loss/infertility counseling by any health care provider, just 41.7% reported that their primary ob.gyn. counseled them about weight loss before referring them for treatment. Infertility specialists seem to provide the most assistance: Nearly 70% of the respondents said they’ve been counseled by these providers.
Women with a higher-than-average BMI (39) were more likely to report a referral to weight loss counseling compared with women not referred (37.9, P = .2).
Investigators also asked patients about their knowledge of obesity and its relationship to other health conditions. About 90% understood that infertility and excess weight were related. Overall, they were less sure about the link between obesity and still birth, breast cancer, and birth defects. Only 37% were able to identify a normal BMI range.
Avoiding a touchy subject
BMI is a highly sensitive area for many women, despite its detrimental effect on fertility, Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida and director of the IVF Center in Orlando, said in an interview.
“By the time their journey has led them to an infertility specialist, most women are very anxious to begin treatment,” said Dr. Trolice, who was not involved in the survey. These patients, however, could interpret any medical advice to achieve a more optimal BMI and healthier lifestyle as a negative judgment that could delay their goal of having a healthy child, he said.
Physicians in turn may avoid these conversations because they don’t want to encourage the ire of patients and/or risk a negative online rating review, he added.
Don’t say ‘just lose weight’
When asked what type of counseling works best, many said that nonspecific recommendations such as “you need to lose weight” or “exercise more” were the least helpful. Targeted advice such as “avoid eating at night and take walks every day,” works more effectively. “Any kind of referral to a bariatrics team or weight loss program was seen as helpful by patients,” said Dr. O’Neill.
Suggestions that considered the difficulty of this process, such as seeking therapy, were also helpful. “Patients appreciated empathy, compassion, and encouragement” from their physicians, she said.
The role of physicians in weight loss
Physicians can make a difference. Studies show that patients who received weight loss counseling were more likely to attempt weight loss and report clinically significant weight loss.
The American College of Obstetricians and Gynecologists and ASRM recommend counseling patients with overweight and obesity to lose weight before getting pregnant. A modest weight loss of 10% is associated with improved ovulatory function and higher pregnancy rates, said Dr. O’Neill.
“Appropriately, the infertility specialist should strongly recommend [that women who are obese] obtain a more optimal BMI prior to fertility treatment. While there is no guarantee of decreased infertility and decreased pregnancy complications following weight loss, a lower BMI improves outcomes,” said Dr. Trolice.
Future research should address the fertility outcomes of women who have been counseled by their providers to lose weight and the most effective method of counseling, noted Dr. O’Neill. “We have to find the best ways to address this at each fertility institution.”
The study had limited generalizability because of its narrow patient population and regional differences in access to insurance and weight loss specialists. COVID-19 also reduced the sample size, said Dr. O’Neill. She noted that patient perceptions might not equate with actual counseling delivered.
Dr. O’Neill and Dr. Trolice had no disclosures.
Physicians could be doing a better job of counseling patients with obesity and overweight on weight loss and fertility. A study of 48 women seeking infertility care at a large academic center found that less than half received advice on weight loss from their primary ob.gyn. prior to referral for infertility treatment.
Patients are thinking about this – many attempt to lose weight independently of support from their health care providers, said lead study author Margaret R. O’Neill, MD, a resident at the University of Massachusetts Medical Center in Worcester. Dr. O’Neill discussed these results at the American Society of Reproductive Medicine’s 2021 meeting.
Nearly half of all U.S. women of reproductive age have overweight or obesity, with a body mass index of >25 kg/m2. Menstrual irregularity, ovulatory dysfunction, reduced fecundity, and lower efficacy of infertility treatment are some of the consequences of obesity on fertility, said Dr. O’Neill. Obesity also affects the health of expectant mothers and fetuses, increasing the likelihood of gestational diabetes, preterm delivery, and preeclampsia, and increased incidence of fetal anomalies.
“Unfortunately, even though the prevalence of obesity has been increasing substantially in our country, there’s not excellent rates of this being addressed by physicians,” said Dr. O’Neill. BMI is often left out of documentation and rates of referrals to weight loss specialists are also low.
Conversations have been taking place about IVF centers instituting different BMI cutoffs for certain types of assisted reproductive technology, she noted.
Dr. O’Neill and her colleagues undertook a survey to see what advice community providers were dispensing about weight management on fertility.
Infertility specialists offer the most guidance
The prospective study included 48 nonpregnant women of reproductive age women presenting for IVF who needed an anesthesia consultation because of elevated BMI (> 35) prior to initiation of IVF. Mean age was 36 years and mean BMI was 38.5. More than 70% of the patients were White and they were predominantly English speakers.
All participants had attempted weight loss, including an attempt in the last year, and 93.8% reported trying to lose weight in the last year. On average, patients weighed about 20 pounds less than their heaviest adult weight. Nineteen percent of the participants were at their heaviest adult weight.
While 60% said they’d received weight loss/infertility counseling by any health care provider, just 41.7% reported that their primary ob.gyn. counseled them about weight loss before referring them for treatment. Infertility specialists seem to provide the most assistance: Nearly 70% of the respondents said they’ve been counseled by these providers.
Women with a higher-than-average BMI (39) were more likely to report a referral to weight loss counseling compared with women not referred (37.9, P = .2).
Investigators also asked patients about their knowledge of obesity and its relationship to other health conditions. About 90% understood that infertility and excess weight were related. Overall, they were less sure about the link between obesity and still birth, breast cancer, and birth defects. Only 37% were able to identify a normal BMI range.
Avoiding a touchy subject
BMI is a highly sensitive area for many women, despite its detrimental effect on fertility, Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida and director of the IVF Center in Orlando, said in an interview.
“By the time their journey has led them to an infertility specialist, most women are very anxious to begin treatment,” said Dr. Trolice, who was not involved in the survey. These patients, however, could interpret any medical advice to achieve a more optimal BMI and healthier lifestyle as a negative judgment that could delay their goal of having a healthy child, he said.
Physicians in turn may avoid these conversations because they don’t want to encourage the ire of patients and/or risk a negative online rating review, he added.
Don’t say ‘just lose weight’
When asked what type of counseling works best, many said that nonspecific recommendations such as “you need to lose weight” or “exercise more” were the least helpful. Targeted advice such as “avoid eating at night and take walks every day,” works more effectively. “Any kind of referral to a bariatrics team or weight loss program was seen as helpful by patients,” said Dr. O’Neill.
Suggestions that considered the difficulty of this process, such as seeking therapy, were also helpful. “Patients appreciated empathy, compassion, and encouragement” from their physicians, she said.
The role of physicians in weight loss
Physicians can make a difference. Studies show that patients who received weight loss counseling were more likely to attempt weight loss and report clinically significant weight loss.
The American College of Obstetricians and Gynecologists and ASRM recommend counseling patients with overweight and obesity to lose weight before getting pregnant. A modest weight loss of 10% is associated with improved ovulatory function and higher pregnancy rates, said Dr. O’Neill.
“Appropriately, the infertility specialist should strongly recommend [that women who are obese] obtain a more optimal BMI prior to fertility treatment. While there is no guarantee of decreased infertility and decreased pregnancy complications following weight loss, a lower BMI improves outcomes,” said Dr. Trolice.
Future research should address the fertility outcomes of women who have been counseled by their providers to lose weight and the most effective method of counseling, noted Dr. O’Neill. “We have to find the best ways to address this at each fertility institution.”
The study had limited generalizability because of its narrow patient population and regional differences in access to insurance and weight loss specialists. COVID-19 also reduced the sample size, said Dr. O’Neill. She noted that patient perceptions might not equate with actual counseling delivered.
Dr. O’Neill and Dr. Trolice had no disclosures.
Physicians could be doing a better job of counseling patients with obesity and overweight on weight loss and fertility. A study of 48 women seeking infertility care at a large academic center found that less than half received advice on weight loss from their primary ob.gyn. prior to referral for infertility treatment.
Patients are thinking about this – many attempt to lose weight independently of support from their health care providers, said lead study author Margaret R. O’Neill, MD, a resident at the University of Massachusetts Medical Center in Worcester. Dr. O’Neill discussed these results at the American Society of Reproductive Medicine’s 2021 meeting.
Nearly half of all U.S. women of reproductive age have overweight or obesity, with a body mass index of >25 kg/m2. Menstrual irregularity, ovulatory dysfunction, reduced fecundity, and lower efficacy of infertility treatment are some of the consequences of obesity on fertility, said Dr. O’Neill. Obesity also affects the health of expectant mothers and fetuses, increasing the likelihood of gestational diabetes, preterm delivery, and preeclampsia, and increased incidence of fetal anomalies.
“Unfortunately, even though the prevalence of obesity has been increasing substantially in our country, there’s not excellent rates of this being addressed by physicians,” said Dr. O’Neill. BMI is often left out of documentation and rates of referrals to weight loss specialists are also low.
Conversations have been taking place about IVF centers instituting different BMI cutoffs for certain types of assisted reproductive technology, she noted.
Dr. O’Neill and her colleagues undertook a survey to see what advice community providers were dispensing about weight management on fertility.
Infertility specialists offer the most guidance
The prospective study included 48 nonpregnant women of reproductive age women presenting for IVF who needed an anesthesia consultation because of elevated BMI (> 35) prior to initiation of IVF. Mean age was 36 years and mean BMI was 38.5. More than 70% of the patients were White and they were predominantly English speakers.
All participants had attempted weight loss, including an attempt in the last year, and 93.8% reported trying to lose weight in the last year. On average, patients weighed about 20 pounds less than their heaviest adult weight. Nineteen percent of the participants were at their heaviest adult weight.
While 60% said they’d received weight loss/infertility counseling by any health care provider, just 41.7% reported that their primary ob.gyn. counseled them about weight loss before referring them for treatment. Infertility specialists seem to provide the most assistance: Nearly 70% of the respondents said they’ve been counseled by these providers.
Women with a higher-than-average BMI (39) were more likely to report a referral to weight loss counseling compared with women not referred (37.9, P = .2).
Investigators also asked patients about their knowledge of obesity and its relationship to other health conditions. About 90% understood that infertility and excess weight were related. Overall, they were less sure about the link between obesity and still birth, breast cancer, and birth defects. Only 37% were able to identify a normal BMI range.
Avoiding a touchy subject
BMI is a highly sensitive area for many women, despite its detrimental effect on fertility, Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida and director of the IVF Center in Orlando, said in an interview.
“By the time their journey has led them to an infertility specialist, most women are very anxious to begin treatment,” said Dr. Trolice, who was not involved in the survey. These patients, however, could interpret any medical advice to achieve a more optimal BMI and healthier lifestyle as a negative judgment that could delay their goal of having a healthy child, he said.
Physicians in turn may avoid these conversations because they don’t want to encourage the ire of patients and/or risk a negative online rating review, he added.
Don’t say ‘just lose weight’
When asked what type of counseling works best, many said that nonspecific recommendations such as “you need to lose weight” or “exercise more” were the least helpful. Targeted advice such as “avoid eating at night and take walks every day,” works more effectively. “Any kind of referral to a bariatrics team or weight loss program was seen as helpful by patients,” said Dr. O’Neill.
Suggestions that considered the difficulty of this process, such as seeking therapy, were also helpful. “Patients appreciated empathy, compassion, and encouragement” from their physicians, she said.
The role of physicians in weight loss
Physicians can make a difference. Studies show that patients who received weight loss counseling were more likely to attempt weight loss and report clinically significant weight loss.
The American College of Obstetricians and Gynecologists and ASRM recommend counseling patients with overweight and obesity to lose weight before getting pregnant. A modest weight loss of 10% is associated with improved ovulatory function and higher pregnancy rates, said Dr. O’Neill.
“Appropriately, the infertility specialist should strongly recommend [that women who are obese] obtain a more optimal BMI prior to fertility treatment. While there is no guarantee of decreased infertility and decreased pregnancy complications following weight loss, a lower BMI improves outcomes,” said Dr. Trolice.
Future research should address the fertility outcomes of women who have been counseled by their providers to lose weight and the most effective method of counseling, noted Dr. O’Neill. “We have to find the best ways to address this at each fertility institution.”
The study had limited generalizability because of its narrow patient population and regional differences in access to insurance and weight loss specialists. COVID-19 also reduced the sample size, said Dr. O’Neill. She noted that patient perceptions might not equate with actual counseling delivered.
Dr. O’Neill and Dr. Trolice had no disclosures.
FROM ASRM 2021
Bone risk: Is time since menopause a better predictor than age?
Although early menopause is linked to increased risks in bone loss and fracture, new research indicates that, even among the majority of women who have menopause after age 45, the time since the final menstrual period can be a stronger predictor than chronological age for key risks in bone health and fracture.
In a large longitudinal cohort, the number of years since a woman’s final menstrual period specifically showed a stronger association with femoral neck bone mineral density (BMD) than chronological age, while an earlier age at menopause – even among those over 45 years, was linked to an increased risk of fracture.
“Most of our clinical tools to predict osteoporosis-related outcomes use chronological age,” first author Albert Shieh, MD, told this news organization.
“Our findings suggest that more research should be done to examine whether ovarian age (time since final menstrual period) should be used in these tools as well.”
An increased focus on the significance of age at the time of the final menstrual period, compared with chronological age, has gained interest in risk assessment because of the known acceleration in the decline of BMD that occurs 1 year prior to the final menstrual period and continues at a rapid pace for 3 years afterwards before slowing.
To further investigate the association with BMD, Dr. Shieh, an endocrinologist specializing in osteoporosis at the University of California, Los Angeles, and his colleagues turned to data from the Study of Women’s Health Across the Nation (SWAN), a longitudinal cohort study of ambulatory women with pre- or early perimenopausal baseline data and 15 annual follow-up assessments.
Outcomes regarding postmenopausal lumbar spine (LS) or femoral neck (FN) BMD were evaluated in 1,038 women, while the time to fracture in relation to the final menstrual period was separately evaluated in 1,554 women.
In both cohorts, the women had a known final menstrual period at age 45 or older, and on average, their final menstrual period occurred at age 52.
After a multivariate adjustment for age, body mass index, and various other factors, they found that each additional year after a woman’s final menstrual period was associated with a significant (0.006 g/cm2) reduction in postmenopausal lumbar spine BMD and a 0.004 g/cm2 reduction femoral neck BMD (both P < .0001).
Conversely, chronological age was not associated with a change in femoral neck BMD when evaluated independently of years since the final menstrual period, the researchers reported in the Journal of Clinical Endocrinology and Metabolism.
Regarding lumbar spine BMD, chronological age was unexpectedly associated not just with change, but in fact with increases in lumbar spine BMD (P < .0001 per year). However, the authors speculate the change “is likely a reflection of age-associated degenerative changes causing false elevations in BMD measured by dual-energy x-ray absorptiometry.”
Fracture risk with earlier menopause
In terms of the fracture risk analysis, despite the women all being aged 45 or older, earlier age at menopause was still tied to an increased risk of incident fracture, with a 5% increase in risk for each earlier year in age at the time of the final menstrual period (P = .02).
Compared with women who had their final menstrual period at age 55, for instance, those who finished menstruating at age 47 had a 6.3% greater 20-year cumulative fracture risk, the authors note.
While previous findings from the Malmo Perimenopausal Study showed menopause prior to the age of 47 to be associated with an 83% and 59% greater risk of densitometric osteoporosis and fracture, respectively, by age 77, the authors note that the new study is unique in including only women who had a final menstrual period over the age of 45, therefore reducing the potential confounding of data on women under 45.
The new results “add to a growing body of literature suggesting that the endocrine changes that occur during the menopause transition trigger a pathophysiologic cascade that leads to organ dysfunction,” the authors note.
In terms of implications in risk assessment, “future studies should examine whether years since the final menstrual period predicts major osteoporotic fractures and hip fractures, specifically, and, if so, whether replacing chronological age with years since the final menstrual period improves the performance of clinical prediction tools, such as FRAX [Fracture Risk Assessment Tool],” they add.
Addition to guidelines?
Commenting on the findings, Peter Ebeling, MD, the current president of the American Society of Bone and Mineral Research, noted that the study importantly “confirms what we had previously anticipated, that in women with menopause who are 45 years of age or older a lower age of final menstrual period is associated with lower spine and hip BMD and more fractures.”
“We had already known this for women with premature ovarian insufficiency or an early menopause, and this extends the observation to the vast majority of women – more than 90% – with a normal menopause age,” said Dr. Ebeling, professor of medicine at Monash Health, Monash University, in Melbourne.
Despite the known importance of the time since final menstrual period, guidelines still focus on age in terms of chronology, rather than biology, emphasizing the risk among women over 50, in general, rather than the time since the last menstrual period, he noted.
“There is an important difference [between those two], as shown by this study,” he said. “Guidelines could be easily adapted to reflect this.”
Specifically, the association between lower age of final menstrual period and lower spine and hip BMD and more fractures requires “more formal assessment to determine whether adding age of final menstrual period to existing fracture risk calculator tools, like FRAX, can improve absolute fracture risk prediction,” Dr. Ebeling noted.
The authors and Dr. Ebeling had no disclosures to report.
Although early menopause is linked to increased risks in bone loss and fracture, new research indicates that, even among the majority of women who have menopause after age 45, the time since the final menstrual period can be a stronger predictor than chronological age for key risks in bone health and fracture.
In a large longitudinal cohort, the number of years since a woman’s final menstrual period specifically showed a stronger association with femoral neck bone mineral density (BMD) than chronological age, while an earlier age at menopause – even among those over 45 years, was linked to an increased risk of fracture.
“Most of our clinical tools to predict osteoporosis-related outcomes use chronological age,” first author Albert Shieh, MD, told this news organization.
“Our findings suggest that more research should be done to examine whether ovarian age (time since final menstrual period) should be used in these tools as well.”
An increased focus on the significance of age at the time of the final menstrual period, compared with chronological age, has gained interest in risk assessment because of the known acceleration in the decline of BMD that occurs 1 year prior to the final menstrual period and continues at a rapid pace for 3 years afterwards before slowing.
To further investigate the association with BMD, Dr. Shieh, an endocrinologist specializing in osteoporosis at the University of California, Los Angeles, and his colleagues turned to data from the Study of Women’s Health Across the Nation (SWAN), a longitudinal cohort study of ambulatory women with pre- or early perimenopausal baseline data and 15 annual follow-up assessments.
Outcomes regarding postmenopausal lumbar spine (LS) or femoral neck (FN) BMD were evaluated in 1,038 women, while the time to fracture in relation to the final menstrual period was separately evaluated in 1,554 women.
In both cohorts, the women had a known final menstrual period at age 45 or older, and on average, their final menstrual period occurred at age 52.
After a multivariate adjustment for age, body mass index, and various other factors, they found that each additional year after a woman’s final menstrual period was associated with a significant (0.006 g/cm2) reduction in postmenopausal lumbar spine BMD and a 0.004 g/cm2 reduction femoral neck BMD (both P < .0001).
Conversely, chronological age was not associated with a change in femoral neck BMD when evaluated independently of years since the final menstrual period, the researchers reported in the Journal of Clinical Endocrinology and Metabolism.
Regarding lumbar spine BMD, chronological age was unexpectedly associated not just with change, but in fact with increases in lumbar spine BMD (P < .0001 per year). However, the authors speculate the change “is likely a reflection of age-associated degenerative changes causing false elevations in BMD measured by dual-energy x-ray absorptiometry.”
Fracture risk with earlier menopause
In terms of the fracture risk analysis, despite the women all being aged 45 or older, earlier age at menopause was still tied to an increased risk of incident fracture, with a 5% increase in risk for each earlier year in age at the time of the final menstrual period (P = .02).
Compared with women who had their final menstrual period at age 55, for instance, those who finished menstruating at age 47 had a 6.3% greater 20-year cumulative fracture risk, the authors note.
While previous findings from the Malmo Perimenopausal Study showed menopause prior to the age of 47 to be associated with an 83% and 59% greater risk of densitometric osteoporosis and fracture, respectively, by age 77, the authors note that the new study is unique in including only women who had a final menstrual period over the age of 45, therefore reducing the potential confounding of data on women under 45.
The new results “add to a growing body of literature suggesting that the endocrine changes that occur during the menopause transition trigger a pathophysiologic cascade that leads to organ dysfunction,” the authors note.
In terms of implications in risk assessment, “future studies should examine whether years since the final menstrual period predicts major osteoporotic fractures and hip fractures, specifically, and, if so, whether replacing chronological age with years since the final menstrual period improves the performance of clinical prediction tools, such as FRAX [Fracture Risk Assessment Tool],” they add.
Addition to guidelines?
Commenting on the findings, Peter Ebeling, MD, the current president of the American Society of Bone and Mineral Research, noted that the study importantly “confirms what we had previously anticipated, that in women with menopause who are 45 years of age or older a lower age of final menstrual period is associated with lower spine and hip BMD and more fractures.”
“We had already known this for women with premature ovarian insufficiency or an early menopause, and this extends the observation to the vast majority of women – more than 90% – with a normal menopause age,” said Dr. Ebeling, professor of medicine at Monash Health, Monash University, in Melbourne.
Despite the known importance of the time since final menstrual period, guidelines still focus on age in terms of chronology, rather than biology, emphasizing the risk among women over 50, in general, rather than the time since the last menstrual period, he noted.
“There is an important difference [between those two], as shown by this study,” he said. “Guidelines could be easily adapted to reflect this.”
Specifically, the association between lower age of final menstrual period and lower spine and hip BMD and more fractures requires “more formal assessment to determine whether adding age of final menstrual period to existing fracture risk calculator tools, like FRAX, can improve absolute fracture risk prediction,” Dr. Ebeling noted.
The authors and Dr. Ebeling had no disclosures to report.
Although early menopause is linked to increased risks in bone loss and fracture, new research indicates that, even among the majority of women who have menopause after age 45, the time since the final menstrual period can be a stronger predictor than chronological age for key risks in bone health and fracture.
In a large longitudinal cohort, the number of years since a woman’s final menstrual period specifically showed a stronger association with femoral neck bone mineral density (BMD) than chronological age, while an earlier age at menopause – even among those over 45 years, was linked to an increased risk of fracture.
“Most of our clinical tools to predict osteoporosis-related outcomes use chronological age,” first author Albert Shieh, MD, told this news organization.
“Our findings suggest that more research should be done to examine whether ovarian age (time since final menstrual period) should be used in these tools as well.”
An increased focus on the significance of age at the time of the final menstrual period, compared with chronological age, has gained interest in risk assessment because of the known acceleration in the decline of BMD that occurs 1 year prior to the final menstrual period and continues at a rapid pace for 3 years afterwards before slowing.
To further investigate the association with BMD, Dr. Shieh, an endocrinologist specializing in osteoporosis at the University of California, Los Angeles, and his colleagues turned to data from the Study of Women’s Health Across the Nation (SWAN), a longitudinal cohort study of ambulatory women with pre- or early perimenopausal baseline data and 15 annual follow-up assessments.
Outcomes regarding postmenopausal lumbar spine (LS) or femoral neck (FN) BMD were evaluated in 1,038 women, while the time to fracture in relation to the final menstrual period was separately evaluated in 1,554 women.
In both cohorts, the women had a known final menstrual period at age 45 or older, and on average, their final menstrual period occurred at age 52.
After a multivariate adjustment for age, body mass index, and various other factors, they found that each additional year after a woman’s final menstrual period was associated with a significant (0.006 g/cm2) reduction in postmenopausal lumbar spine BMD and a 0.004 g/cm2 reduction femoral neck BMD (both P < .0001).
Conversely, chronological age was not associated with a change in femoral neck BMD when evaluated independently of years since the final menstrual period, the researchers reported in the Journal of Clinical Endocrinology and Metabolism.
Regarding lumbar spine BMD, chronological age was unexpectedly associated not just with change, but in fact with increases in lumbar spine BMD (P < .0001 per year). However, the authors speculate the change “is likely a reflection of age-associated degenerative changes causing false elevations in BMD measured by dual-energy x-ray absorptiometry.”
Fracture risk with earlier menopause
In terms of the fracture risk analysis, despite the women all being aged 45 or older, earlier age at menopause was still tied to an increased risk of incident fracture, with a 5% increase in risk for each earlier year in age at the time of the final menstrual period (P = .02).
Compared with women who had their final menstrual period at age 55, for instance, those who finished menstruating at age 47 had a 6.3% greater 20-year cumulative fracture risk, the authors note.
While previous findings from the Malmo Perimenopausal Study showed menopause prior to the age of 47 to be associated with an 83% and 59% greater risk of densitometric osteoporosis and fracture, respectively, by age 77, the authors note that the new study is unique in including only women who had a final menstrual period over the age of 45, therefore reducing the potential confounding of data on women under 45.
The new results “add to a growing body of literature suggesting that the endocrine changes that occur during the menopause transition trigger a pathophysiologic cascade that leads to organ dysfunction,” the authors note.
In terms of implications in risk assessment, “future studies should examine whether years since the final menstrual period predicts major osteoporotic fractures and hip fractures, specifically, and, if so, whether replacing chronological age with years since the final menstrual period improves the performance of clinical prediction tools, such as FRAX [Fracture Risk Assessment Tool],” they add.
Addition to guidelines?
Commenting on the findings, Peter Ebeling, MD, the current president of the American Society of Bone and Mineral Research, noted that the study importantly “confirms what we had previously anticipated, that in women with menopause who are 45 years of age or older a lower age of final menstrual period is associated with lower spine and hip BMD and more fractures.”
“We had already known this for women with premature ovarian insufficiency or an early menopause, and this extends the observation to the vast majority of women – more than 90% – with a normal menopause age,” said Dr. Ebeling, professor of medicine at Monash Health, Monash University, in Melbourne.
Despite the known importance of the time since final menstrual period, guidelines still focus on age in terms of chronology, rather than biology, emphasizing the risk among women over 50, in general, rather than the time since the last menstrual period, he noted.
“There is an important difference [between those two], as shown by this study,” he said. “Guidelines could be easily adapted to reflect this.”
Specifically, the association between lower age of final menstrual period and lower spine and hip BMD and more fractures requires “more formal assessment to determine whether adding age of final menstrual period to existing fracture risk calculator tools, like FRAX, can improve absolute fracture risk prediction,” Dr. Ebeling noted.
The authors and Dr. Ebeling had no disclosures to report.
FROM JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
White House unveils plan to combat endocrine-disrupting PFAS pollution
The federal government is stepping up actions to protect Americans from per- and polyfluoroalkyl substances that continue to threaten health through pollution in the air, water, and foods, according to a statement from the White House on Oct. 18.
The comprehensive plan includes efforts to prevent per- and polyfluoroalkyl substances (PFAS) from being released into the air, drinking and ground water, and the food supply chain, according to the statement. Other efforts will expand cleanup and remediation of the impact of PFAS already present in the environment.
PFAS are a category of endocrine-disrupting chemicals (EDCs) that have been used for decades in a range of consumer products including cookware, stain-resistant clothes, fast food wrappers, treatments for carpets and furniture, and firefighting foams. PFAS can be released into the air, and also into surface water, drinking water, and ground water, because of how they are disposed, according to a 2020 report from the Endocrine Society and the International Pollutants Elimination Network. The report suggested that creation of more plastic products will likely increase exposure to PFAS and other EDCs.
The Environmental Protection Agency will take the lead on the Biden administration’s PFAS reduction efforts. The agency announced a PFAS Roadmap, which outlines actions to control PFAS over the next 3 years. The Roadmap’s goals include keeping PFAS out of the environment, holding polluters accountable for their actions, investing in scientific research to learn more about the impact of PFAS on human health, and prioritizing protection for disadvantaged communities. The EPA described its approach to PFAS as three pronged (Research, Restrict, Remediate). Planned actions noted on the EPA website include publication of a national PFAS testing strategy, establishing an improved review process for new PFAS, reviewing existing PFAS, and enhancing reporting to track sources and quantities of PFAS.
White House statement noted that other agencies committed to controlling PFAS include the Department of Defense, which will conduct cleanups and assessments at DOD and National Guard locations; the Food and Drug Administration, which will to expand its food supply testing to estimate dietary exposure to PFAS; and the Department of Agriculture, which is investigating causes and impacts of PFAS in the food system, and supporting research on environmental contaminants including PFAS.
The Department of Homeland Security has conducted an inventory of PFAS use, notably the use of PFAS in firefighting foams, and established an Emerging Contaminants Working Group to remediate PFAS and other contaminants. In addition, the Department of Health & Human Services monitors the evolving science on human health and PFAS and anticipates a report by the Centers for Disease Control and Prevention on the health effects of PFAS exposure, with data from eight states.
The American Chemistry Council (ACC), a trade association for American chemistry companies, issued a statement in response to the EPA’s PFAS Strategic Roadmap in which they supported the value of science-based regulation, but emphasized that PFAS are distinct from one another, and should not be grouped together for regulation purposes.
“According to EPA, approximately 600 PFAS substances are manufactured or in use today, each with its own unique properties and uses, from cellphones to solar panels, for which alternatives are not always available,” according to the ACC statement. “EPA’s Roadmap reinforces the differences between these chemistries and that they should not all be grouped together.” The newly formed Interagency Policy Committee on PFAS will coordinate PFAS response efforts across agencies and “help develop new policy strategies to support research, remediation, and removal of PFAS in communities across the country,” according to the White House statement.
The federal government is stepping up actions to protect Americans from per- and polyfluoroalkyl substances that continue to threaten health through pollution in the air, water, and foods, according to a statement from the White House on Oct. 18.
The comprehensive plan includes efforts to prevent per- and polyfluoroalkyl substances (PFAS) from being released into the air, drinking and ground water, and the food supply chain, according to the statement. Other efforts will expand cleanup and remediation of the impact of PFAS already present in the environment.
PFAS are a category of endocrine-disrupting chemicals (EDCs) that have been used for decades in a range of consumer products including cookware, stain-resistant clothes, fast food wrappers, treatments for carpets and furniture, and firefighting foams. PFAS can be released into the air, and also into surface water, drinking water, and ground water, because of how they are disposed, according to a 2020 report from the Endocrine Society and the International Pollutants Elimination Network. The report suggested that creation of more plastic products will likely increase exposure to PFAS and other EDCs.
The Environmental Protection Agency will take the lead on the Biden administration’s PFAS reduction efforts. The agency announced a PFAS Roadmap, which outlines actions to control PFAS over the next 3 years. The Roadmap’s goals include keeping PFAS out of the environment, holding polluters accountable for their actions, investing in scientific research to learn more about the impact of PFAS on human health, and prioritizing protection for disadvantaged communities. The EPA described its approach to PFAS as three pronged (Research, Restrict, Remediate). Planned actions noted on the EPA website include publication of a national PFAS testing strategy, establishing an improved review process for new PFAS, reviewing existing PFAS, and enhancing reporting to track sources and quantities of PFAS.
White House statement noted that other agencies committed to controlling PFAS include the Department of Defense, which will conduct cleanups and assessments at DOD and National Guard locations; the Food and Drug Administration, which will to expand its food supply testing to estimate dietary exposure to PFAS; and the Department of Agriculture, which is investigating causes and impacts of PFAS in the food system, and supporting research on environmental contaminants including PFAS.
The Department of Homeland Security has conducted an inventory of PFAS use, notably the use of PFAS in firefighting foams, and established an Emerging Contaminants Working Group to remediate PFAS and other contaminants. In addition, the Department of Health & Human Services monitors the evolving science on human health and PFAS and anticipates a report by the Centers for Disease Control and Prevention on the health effects of PFAS exposure, with data from eight states.
The American Chemistry Council (ACC), a trade association for American chemistry companies, issued a statement in response to the EPA’s PFAS Strategic Roadmap in which they supported the value of science-based regulation, but emphasized that PFAS are distinct from one another, and should not be grouped together for regulation purposes.
“According to EPA, approximately 600 PFAS substances are manufactured or in use today, each with its own unique properties and uses, from cellphones to solar panels, for which alternatives are not always available,” according to the ACC statement. “EPA’s Roadmap reinforces the differences between these chemistries and that they should not all be grouped together.” The newly formed Interagency Policy Committee on PFAS will coordinate PFAS response efforts across agencies and “help develop new policy strategies to support research, remediation, and removal of PFAS in communities across the country,” according to the White House statement.
The federal government is stepping up actions to protect Americans from per- and polyfluoroalkyl substances that continue to threaten health through pollution in the air, water, and foods, according to a statement from the White House on Oct. 18.
The comprehensive plan includes efforts to prevent per- and polyfluoroalkyl substances (PFAS) from being released into the air, drinking and ground water, and the food supply chain, according to the statement. Other efforts will expand cleanup and remediation of the impact of PFAS already present in the environment.
PFAS are a category of endocrine-disrupting chemicals (EDCs) that have been used for decades in a range of consumer products including cookware, stain-resistant clothes, fast food wrappers, treatments for carpets and furniture, and firefighting foams. PFAS can be released into the air, and also into surface water, drinking water, and ground water, because of how they are disposed, according to a 2020 report from the Endocrine Society and the International Pollutants Elimination Network. The report suggested that creation of more plastic products will likely increase exposure to PFAS and other EDCs.
The Environmental Protection Agency will take the lead on the Biden administration’s PFAS reduction efforts. The agency announced a PFAS Roadmap, which outlines actions to control PFAS over the next 3 years. The Roadmap’s goals include keeping PFAS out of the environment, holding polluters accountable for their actions, investing in scientific research to learn more about the impact of PFAS on human health, and prioritizing protection for disadvantaged communities. The EPA described its approach to PFAS as three pronged (Research, Restrict, Remediate). Planned actions noted on the EPA website include publication of a national PFAS testing strategy, establishing an improved review process for new PFAS, reviewing existing PFAS, and enhancing reporting to track sources and quantities of PFAS.
White House statement noted that other agencies committed to controlling PFAS include the Department of Defense, which will conduct cleanups and assessments at DOD and National Guard locations; the Food and Drug Administration, which will to expand its food supply testing to estimate dietary exposure to PFAS; and the Department of Agriculture, which is investigating causes and impacts of PFAS in the food system, and supporting research on environmental contaminants including PFAS.
The Department of Homeland Security has conducted an inventory of PFAS use, notably the use of PFAS in firefighting foams, and established an Emerging Contaminants Working Group to remediate PFAS and other contaminants. In addition, the Department of Health & Human Services monitors the evolving science on human health and PFAS and anticipates a report by the Centers for Disease Control and Prevention on the health effects of PFAS exposure, with data from eight states.
The American Chemistry Council (ACC), a trade association for American chemistry companies, issued a statement in response to the EPA’s PFAS Strategic Roadmap in which they supported the value of science-based regulation, but emphasized that PFAS are distinct from one another, and should not be grouped together for regulation purposes.
“According to EPA, approximately 600 PFAS substances are manufactured or in use today, each with its own unique properties and uses, from cellphones to solar panels, for which alternatives are not always available,” according to the ACC statement. “EPA’s Roadmap reinforces the differences between these chemistries and that they should not all be grouped together.” The newly formed Interagency Policy Committee on PFAS will coordinate PFAS response efforts across agencies and “help develop new policy strategies to support research, remediation, and removal of PFAS in communities across the country,” according to the White House statement.
Synthetic chemical in consumer products linked to early death, study says
Daily exposure to phthalates, which are synthetic chemicals founds in many consumer products, may lead to hundreds of thousands of early deaths each year among older adults in the United States, according to a new study published Oct. 12, 2021, in the peer-reviewed journal Environmental Pollution.
The chemicals are found in hundreds of types of products, including children’s toys, food storage containers, makeup, perfume, and shampoo. In the study, those with the highest levels of phthalates had a greater risk of death from any cause, especially heart disease.
“This study adds to the growing database on the impact of plastics on the human body and bolsters public health and business cases for reducing or eliminating the use of plastics,” Leonardo Trasande, MD, the lead author and a professor of environmental medicine and population health at New York University Langone Health, told CNN.
Dr. Trasande and colleagues measured the urine concentration of phthalates in more than 5,000 adults aged 55-64 and compared the levels with the risk of early death over an average of 10 years. The research team controlled for preexisting heart diseases, diabetes, cancer, poor eating habits, physical activity, body mass, and other known hormone disruptors such as bisphenol A, or BPA, an industrial chemical that’s been used since the 1950s to make certain plastics and resins, according to the Mayo Clinic
The research team found that phthalates could contribute to 91,000-107,000 premature deaths per year in the United States. These early deaths could cost the nation $40 billion to $47 billion each year in lost economic productivity.
Phthalates interrupt the body’s endocrine system and hormone production. Previous studies have found that the chemicals are linked with developmental, reproductive, and immune system problems, according to NYU Langone Health. They’ve also been linked with asthma, childhood obesity, heart issues, and cancer.
“These chemicals have a rap sheet,” Dr. Trasande told CNN. “And the fact of the matter is that when you look at the entire body of evidence, it provides a haunting pattern of concern.”
Phthalates are often called “everywhere chemicals” because they are so common, CNN reported. Also called “plasticizers,” they are added to products to make them more durable, including PVC plumbing, vinyl flooring, medical tubing, garden hoses, food packaging, detergents, clothing, furniture, and automotive materials.
People are often exposed when they breathe contaminated air or consume food that comes into contact with the chemical, according to the Centers for Disease Control and Prevention. Children may be exposed by touching plastic items and putting their hands in their mouth.
Dr. Trasande told CNN that it’s possible to lessen exposure to phthalates and other endocrine disruptors such as BPA by using unscented lotions, laundry detergents, and cleaning supplies, as well as substituting glass, stainless steel, ceramic, and wood for plastic food storage.
“First, avoid plastics as much as you can. Never put plastic containers in the microwave or dishwasher, where the heat can break down the linings so they might be absorbed more readily,” he said. “In addition, cooking at home and reducing your use of processed foods can reduce the levels of the chemical exposures you come in contact with.”
A version of this article first appeared on WebMD.com.
Daily exposure to phthalates, which are synthetic chemicals founds in many consumer products, may lead to hundreds of thousands of early deaths each year among older adults in the United States, according to a new study published Oct. 12, 2021, in the peer-reviewed journal Environmental Pollution.
The chemicals are found in hundreds of types of products, including children’s toys, food storage containers, makeup, perfume, and shampoo. In the study, those with the highest levels of phthalates had a greater risk of death from any cause, especially heart disease.
“This study adds to the growing database on the impact of plastics on the human body and bolsters public health and business cases for reducing or eliminating the use of plastics,” Leonardo Trasande, MD, the lead author and a professor of environmental medicine and population health at New York University Langone Health, told CNN.
Dr. Trasande and colleagues measured the urine concentration of phthalates in more than 5,000 adults aged 55-64 and compared the levels with the risk of early death over an average of 10 years. The research team controlled for preexisting heart diseases, diabetes, cancer, poor eating habits, physical activity, body mass, and other known hormone disruptors such as bisphenol A, or BPA, an industrial chemical that’s been used since the 1950s to make certain plastics and resins, according to the Mayo Clinic
The research team found that phthalates could contribute to 91,000-107,000 premature deaths per year in the United States. These early deaths could cost the nation $40 billion to $47 billion each year in lost economic productivity.
Phthalates interrupt the body’s endocrine system and hormone production. Previous studies have found that the chemicals are linked with developmental, reproductive, and immune system problems, according to NYU Langone Health. They’ve also been linked with asthma, childhood obesity, heart issues, and cancer.
“These chemicals have a rap sheet,” Dr. Trasande told CNN. “And the fact of the matter is that when you look at the entire body of evidence, it provides a haunting pattern of concern.”
Phthalates are often called “everywhere chemicals” because they are so common, CNN reported. Also called “plasticizers,” they are added to products to make them more durable, including PVC plumbing, vinyl flooring, medical tubing, garden hoses, food packaging, detergents, clothing, furniture, and automotive materials.
People are often exposed when they breathe contaminated air or consume food that comes into contact with the chemical, according to the Centers for Disease Control and Prevention. Children may be exposed by touching plastic items and putting their hands in their mouth.
Dr. Trasande told CNN that it’s possible to lessen exposure to phthalates and other endocrine disruptors such as BPA by using unscented lotions, laundry detergents, and cleaning supplies, as well as substituting glass, stainless steel, ceramic, and wood for plastic food storage.
“First, avoid plastics as much as you can. Never put plastic containers in the microwave or dishwasher, where the heat can break down the linings so they might be absorbed more readily,” he said. “In addition, cooking at home and reducing your use of processed foods can reduce the levels of the chemical exposures you come in contact with.”
A version of this article first appeared on WebMD.com.
Daily exposure to phthalates, which are synthetic chemicals founds in many consumer products, may lead to hundreds of thousands of early deaths each year among older adults in the United States, according to a new study published Oct. 12, 2021, in the peer-reviewed journal Environmental Pollution.
The chemicals are found in hundreds of types of products, including children’s toys, food storage containers, makeup, perfume, and shampoo. In the study, those with the highest levels of phthalates had a greater risk of death from any cause, especially heart disease.
“This study adds to the growing database on the impact of plastics on the human body and bolsters public health and business cases for reducing or eliminating the use of plastics,” Leonardo Trasande, MD, the lead author and a professor of environmental medicine and population health at New York University Langone Health, told CNN.
Dr. Trasande and colleagues measured the urine concentration of phthalates in more than 5,000 adults aged 55-64 and compared the levels with the risk of early death over an average of 10 years. The research team controlled for preexisting heart diseases, diabetes, cancer, poor eating habits, physical activity, body mass, and other known hormone disruptors such as bisphenol A, or BPA, an industrial chemical that’s been used since the 1950s to make certain plastics and resins, according to the Mayo Clinic
The research team found that phthalates could contribute to 91,000-107,000 premature deaths per year in the United States. These early deaths could cost the nation $40 billion to $47 billion each year in lost economic productivity.
Phthalates interrupt the body’s endocrine system and hormone production. Previous studies have found that the chemicals are linked with developmental, reproductive, and immune system problems, according to NYU Langone Health. They’ve also been linked with asthma, childhood obesity, heart issues, and cancer.
“These chemicals have a rap sheet,” Dr. Trasande told CNN. “And the fact of the matter is that when you look at the entire body of evidence, it provides a haunting pattern of concern.”
Phthalates are often called “everywhere chemicals” because they are so common, CNN reported. Also called “plasticizers,” they are added to products to make them more durable, including PVC plumbing, vinyl flooring, medical tubing, garden hoses, food packaging, detergents, clothing, furniture, and automotive materials.
People are often exposed when they breathe contaminated air or consume food that comes into contact with the chemical, according to the Centers for Disease Control and Prevention. Children may be exposed by touching plastic items and putting their hands in their mouth.
Dr. Trasande told CNN that it’s possible to lessen exposure to phthalates and other endocrine disruptors such as BPA by using unscented lotions, laundry detergents, and cleaning supplies, as well as substituting glass, stainless steel, ceramic, and wood for plastic food storage.
“First, avoid plastics as much as you can. Never put plastic containers in the microwave or dishwasher, where the heat can break down the linings so they might be absorbed more readily,” he said. “In addition, cooking at home and reducing your use of processed foods can reduce the levels of the chemical exposures you come in contact with.”
A version of this article first appeared on WebMD.com.
Optimizing thyroid management in reproduction
The attraction of reproductive endocrinology and infertility (REI), personally, is the hormonal interplay of the hypothalamus and pituitary with the end organs that are intimately involved in female reproduction. While the sex hormone–producing organs, such as the ovaries and adrenal glands, are directly related to reproductive function, the thyroid gland is typically overlooked until dysfunction occurs, resulting in ovulation dysfunction and pregnancy complications, namely miscarriage and preterm labor. This month we address thyroid function, given its vital role for fertility and pregnancy health and the fetus’ reliance on maternal thyroid hormone during the first trimester to ensure normal neurologic development.
Thyroid disease is the second most common endocrine disorder affecting women of reproductive age; the first being polycystic ovary syndrome (PCOS). Thyroid dysfunction can impair ovulation and, consequently, fertility. Hyperthyroidism is found in approximately 2.3% of women presenting with fertility problems, compared with 1.5% of women in the general population. Hypothyroidism affects 0.5% of women of reproductive age and has been shown to result in impaired reproductive outcomes, including miscarriage, along with adverse obstetric and fetal outcomes. Subclinical hypothyroidism (SCH), defined as an elevated thyroid-stimulating hormone (TSH) level with a normal free T4, has an incidence of 4%-8% in the reproductive-age population. While there is fair evidence SCH increases miscarriage, treatment may result in improved outcomes.
The prevalence of thyroid autoimmunity (TAI) among women of reproductive age is 8%-14% worldwide and it is increased in the infertility population. TAI, defined as the presence of thyroid peroxidase and thyroglobulin antibodies, has been shown to be associated with a reduced live birth rate, increase in preterm birth, and a two- to threefold increase in miscarriage.
The endocrinologic “pendulum” of guidance regarding the effect on and management of thyroid function regarding fertility, pregnancy, and baby has conflicting results. Controlled ovarian hyperstimulation for in vitro fertilization appears to alter TSH levels and levothyroxine requirements increase in the first trimester by approximately 50%. The controversy lies in which population of women should be tested for TAI, which TSH level is acceptable, and how to manage, if at all, euthyroid women with TAI or women with SCH who are trying to conceive. Ultimately, which women would benefit from levothyroxine while trying to conceive and during pregnancy?
Summary of salient studies
- In a meta-analysis, untreated women with SCH had a higher prevalence of miscarriage, compared with euthyroid women (RR, 1.90). Miscarriage rates were even higher in SCH with TIA, compared with women with SCH. The authors recommend “early treatments to avoid adverse pregnancy outcomes and complications.”
- A randomized controlled trial from China studied women who were euthyroid with TAI undergoing IVF. The authors demonstrated levothyroxine did not reduce miscarriage rates or increase live birth rates. To dive further into their cohort, the authors addressed whether TSH above 2.5 mIU/L or above 4 mIU/L (per the American Society for Reproductive Medicine cutoff values) impaired reproductive outcome and found no benefit of levothyroxine in any subgroup. This is consistent with other studies that showed no detrimental effect on pregnancy outcome with TSH levels above 2.5 mIU/L in the normal range and no reduction in miscarriage with the addition of levothyroxine.
- An observational cohort study of IVF patients that underwent preimplantation genetic testing for aneuploidy did not demonstrate an association between chromosomally normal embryos that miscarried and maternal antithyroid antibodies in recurrent miscarriage patients.
- A double-blind, placebo-controlled trial on the use of levothyroxine in euthyroid women with TAI did not result in a higher rate of live births, lower rate of pregnancy loss, or preterm birth, compared with placebo.
Consensus statements
- The American Society for Reproductive Medicine considers it reasonable to test infertile women trying to conceive and to treat SCH with levothyroxine to maintain a TSH less than 2.5 mIU/L and within the normal range. Women who have TAI and TSH greater than 2.5 mIU/L can be considered for treatment with levothyroxine.
- The Endocrine Society recommends levothyroxine in women with SCH who have TAI.
- The American Thyroid Association guideline recommends women with SCH who are undergoing IVF be treated with levothyroxine to achieve a TSH concentration less than 2.5mIU/L.
- The 2011 guidelines of the American Thyroid Association and the 2012 guidelines of the Endocrine Society recommended the specific reference ranges for TSH in the early, middle, and late stages of pregnancy as 0.1-2.5 mIU/L, 0.2-3.0 mIU/L, and 0.3-3.0 mIU/L, respectively.
- The American College of Obstetricians & Gynecologists recommend avoiding universal thyroid screening in pregnancy since “identification and treatment of maternal subclinical hypothyroidism has not been shown to result in improved pregnancy outcomes and neurocognitive function in offspring.”
Conclusion
The 2019 Cochrane Database states there are no clear conclusions regarding treatment with levothyroxine in euthyroid TAI or SCH because of the low quality of evidence reported. While TAI and SCH have been associated with pregnancy complications, there is no apparent benefit of levothyroxine in women with TAI or TSH levels between 2.5 and 4 mIU/L.
So, the conundrum is which preconception women to test and how to manage nonovert thyroid disease. For now, it is reasonable to obtain a serum TSH on all women desiring fertility, to treat SCH with levothyroxine to maintain TSH less than 2.5 mIU/L in the normal range, and to adjust levothyroxine accordingly throughout pregnancy.
Dr. Trolice is director of fertility at CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no disclosures. Email him at [email protected].
The attraction of reproductive endocrinology and infertility (REI), personally, is the hormonal interplay of the hypothalamus and pituitary with the end organs that are intimately involved in female reproduction. While the sex hormone–producing organs, such as the ovaries and adrenal glands, are directly related to reproductive function, the thyroid gland is typically overlooked until dysfunction occurs, resulting in ovulation dysfunction and pregnancy complications, namely miscarriage and preterm labor. This month we address thyroid function, given its vital role for fertility and pregnancy health and the fetus’ reliance on maternal thyroid hormone during the first trimester to ensure normal neurologic development.
Thyroid disease is the second most common endocrine disorder affecting women of reproductive age; the first being polycystic ovary syndrome (PCOS). Thyroid dysfunction can impair ovulation and, consequently, fertility. Hyperthyroidism is found in approximately 2.3% of women presenting with fertility problems, compared with 1.5% of women in the general population. Hypothyroidism affects 0.5% of women of reproductive age and has been shown to result in impaired reproductive outcomes, including miscarriage, along with adverse obstetric and fetal outcomes. Subclinical hypothyroidism (SCH), defined as an elevated thyroid-stimulating hormone (TSH) level with a normal free T4, has an incidence of 4%-8% in the reproductive-age population. While there is fair evidence SCH increases miscarriage, treatment may result in improved outcomes.
The prevalence of thyroid autoimmunity (TAI) among women of reproductive age is 8%-14% worldwide and it is increased in the infertility population. TAI, defined as the presence of thyroid peroxidase and thyroglobulin antibodies, has been shown to be associated with a reduced live birth rate, increase in preterm birth, and a two- to threefold increase in miscarriage.
The endocrinologic “pendulum” of guidance regarding the effect on and management of thyroid function regarding fertility, pregnancy, and baby has conflicting results. Controlled ovarian hyperstimulation for in vitro fertilization appears to alter TSH levels and levothyroxine requirements increase in the first trimester by approximately 50%. The controversy lies in which population of women should be tested for TAI, which TSH level is acceptable, and how to manage, if at all, euthyroid women with TAI or women with SCH who are trying to conceive. Ultimately, which women would benefit from levothyroxine while trying to conceive and during pregnancy?
Summary of salient studies
- In a meta-analysis, untreated women with SCH had a higher prevalence of miscarriage, compared with euthyroid women (RR, 1.90). Miscarriage rates were even higher in SCH with TIA, compared with women with SCH. The authors recommend “early treatments to avoid adverse pregnancy outcomes and complications.”
- A randomized controlled trial from China studied women who were euthyroid with TAI undergoing IVF. The authors demonstrated levothyroxine did not reduce miscarriage rates or increase live birth rates. To dive further into their cohort, the authors addressed whether TSH above 2.5 mIU/L or above 4 mIU/L (per the American Society for Reproductive Medicine cutoff values) impaired reproductive outcome and found no benefit of levothyroxine in any subgroup. This is consistent with other studies that showed no detrimental effect on pregnancy outcome with TSH levels above 2.5 mIU/L in the normal range and no reduction in miscarriage with the addition of levothyroxine.
- An observational cohort study of IVF patients that underwent preimplantation genetic testing for aneuploidy did not demonstrate an association between chromosomally normal embryos that miscarried and maternal antithyroid antibodies in recurrent miscarriage patients.
- A double-blind, placebo-controlled trial on the use of levothyroxine in euthyroid women with TAI did not result in a higher rate of live births, lower rate of pregnancy loss, or preterm birth, compared with placebo.
Consensus statements
- The American Society for Reproductive Medicine considers it reasonable to test infertile women trying to conceive and to treat SCH with levothyroxine to maintain a TSH less than 2.5 mIU/L and within the normal range. Women who have TAI and TSH greater than 2.5 mIU/L can be considered for treatment with levothyroxine.
- The Endocrine Society recommends levothyroxine in women with SCH who have TAI.
- The American Thyroid Association guideline recommends women with SCH who are undergoing IVF be treated with levothyroxine to achieve a TSH concentration less than 2.5mIU/L.
- The 2011 guidelines of the American Thyroid Association and the 2012 guidelines of the Endocrine Society recommended the specific reference ranges for TSH in the early, middle, and late stages of pregnancy as 0.1-2.5 mIU/L, 0.2-3.0 mIU/L, and 0.3-3.0 mIU/L, respectively.
- The American College of Obstetricians & Gynecologists recommend avoiding universal thyroid screening in pregnancy since “identification and treatment of maternal subclinical hypothyroidism has not been shown to result in improved pregnancy outcomes and neurocognitive function in offspring.”
Conclusion
The 2019 Cochrane Database states there are no clear conclusions regarding treatment with levothyroxine in euthyroid TAI or SCH because of the low quality of evidence reported. While TAI and SCH have been associated with pregnancy complications, there is no apparent benefit of levothyroxine in women with TAI or TSH levels between 2.5 and 4 mIU/L.
So, the conundrum is which preconception women to test and how to manage nonovert thyroid disease. For now, it is reasonable to obtain a serum TSH on all women desiring fertility, to treat SCH with levothyroxine to maintain TSH less than 2.5 mIU/L in the normal range, and to adjust levothyroxine accordingly throughout pregnancy.
Dr. Trolice is director of fertility at CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no disclosures. Email him at [email protected].
The attraction of reproductive endocrinology and infertility (REI), personally, is the hormonal interplay of the hypothalamus and pituitary with the end organs that are intimately involved in female reproduction. While the sex hormone–producing organs, such as the ovaries and adrenal glands, are directly related to reproductive function, the thyroid gland is typically overlooked until dysfunction occurs, resulting in ovulation dysfunction and pregnancy complications, namely miscarriage and preterm labor. This month we address thyroid function, given its vital role for fertility and pregnancy health and the fetus’ reliance on maternal thyroid hormone during the first trimester to ensure normal neurologic development.
Thyroid disease is the second most common endocrine disorder affecting women of reproductive age; the first being polycystic ovary syndrome (PCOS). Thyroid dysfunction can impair ovulation and, consequently, fertility. Hyperthyroidism is found in approximately 2.3% of women presenting with fertility problems, compared with 1.5% of women in the general population. Hypothyroidism affects 0.5% of women of reproductive age and has been shown to result in impaired reproductive outcomes, including miscarriage, along with adverse obstetric and fetal outcomes. Subclinical hypothyroidism (SCH), defined as an elevated thyroid-stimulating hormone (TSH) level with a normal free T4, has an incidence of 4%-8% in the reproductive-age population. While there is fair evidence SCH increases miscarriage, treatment may result in improved outcomes.
The prevalence of thyroid autoimmunity (TAI) among women of reproductive age is 8%-14% worldwide and it is increased in the infertility population. TAI, defined as the presence of thyroid peroxidase and thyroglobulin antibodies, has been shown to be associated with a reduced live birth rate, increase in preterm birth, and a two- to threefold increase in miscarriage.
The endocrinologic “pendulum” of guidance regarding the effect on and management of thyroid function regarding fertility, pregnancy, and baby has conflicting results. Controlled ovarian hyperstimulation for in vitro fertilization appears to alter TSH levels and levothyroxine requirements increase in the first trimester by approximately 50%. The controversy lies in which population of women should be tested for TAI, which TSH level is acceptable, and how to manage, if at all, euthyroid women with TAI or women with SCH who are trying to conceive. Ultimately, which women would benefit from levothyroxine while trying to conceive and during pregnancy?
Summary of salient studies
- In a meta-analysis, untreated women with SCH had a higher prevalence of miscarriage, compared with euthyroid women (RR, 1.90). Miscarriage rates were even higher in SCH with TIA, compared with women with SCH. The authors recommend “early treatments to avoid adverse pregnancy outcomes and complications.”
- A randomized controlled trial from China studied women who were euthyroid with TAI undergoing IVF. The authors demonstrated levothyroxine did not reduce miscarriage rates or increase live birth rates. To dive further into their cohort, the authors addressed whether TSH above 2.5 mIU/L or above 4 mIU/L (per the American Society for Reproductive Medicine cutoff values) impaired reproductive outcome and found no benefit of levothyroxine in any subgroup. This is consistent with other studies that showed no detrimental effect on pregnancy outcome with TSH levels above 2.5 mIU/L in the normal range and no reduction in miscarriage with the addition of levothyroxine.
- An observational cohort study of IVF patients that underwent preimplantation genetic testing for aneuploidy did not demonstrate an association between chromosomally normal embryos that miscarried and maternal antithyroid antibodies in recurrent miscarriage patients.
- A double-blind, placebo-controlled trial on the use of levothyroxine in euthyroid women with TAI did not result in a higher rate of live births, lower rate of pregnancy loss, or preterm birth, compared with placebo.
Consensus statements
- The American Society for Reproductive Medicine considers it reasonable to test infertile women trying to conceive and to treat SCH with levothyroxine to maintain a TSH less than 2.5 mIU/L and within the normal range. Women who have TAI and TSH greater than 2.5 mIU/L can be considered for treatment with levothyroxine.
- The Endocrine Society recommends levothyroxine in women with SCH who have TAI.
- The American Thyroid Association guideline recommends women with SCH who are undergoing IVF be treated with levothyroxine to achieve a TSH concentration less than 2.5mIU/L.
- The 2011 guidelines of the American Thyroid Association and the 2012 guidelines of the Endocrine Society recommended the specific reference ranges for TSH in the early, middle, and late stages of pregnancy as 0.1-2.5 mIU/L, 0.2-3.0 mIU/L, and 0.3-3.0 mIU/L, respectively.
- The American College of Obstetricians & Gynecologists recommend avoiding universal thyroid screening in pregnancy since “identification and treatment of maternal subclinical hypothyroidism has not been shown to result in improved pregnancy outcomes and neurocognitive function in offspring.”
Conclusion
The 2019 Cochrane Database states there are no clear conclusions regarding treatment with levothyroxine in euthyroid TAI or SCH because of the low quality of evidence reported. While TAI and SCH have been associated with pregnancy complications, there is no apparent benefit of levothyroxine in women with TAI or TSH levels between 2.5 and 4 mIU/L.
So, the conundrum is which preconception women to test and how to manage nonovert thyroid disease. For now, it is reasonable to obtain a serum TSH on all women desiring fertility, to treat SCH with levothyroxine to maintain TSH less than 2.5 mIU/L in the normal range, and to adjust levothyroxine accordingly throughout pregnancy.
Dr. Trolice is director of fertility at CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no disclosures. Email him at [email protected].