Jeff Craven

PHILADELPHIA – When the male partner used marijuana one or more times per week before conception, couples had a higher rate of spontaneous abortion, compared with infrequent use or no use of marijuana by the male partner, Alyssa F. Harlow, MPH, reported at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The male partner’s use of marijuana “one or more times per week in the past 2 months during the preconception period in our study was associated with an increased risk of spontaneous abortion,” said Ms. Harlow, a PhD candidate at Boston University. “The association attenuated for later pregnancy losses, and persisted for those with shorter [pregnancy] attempt time at [study] entry.”

Ms. Harlow and colleagues prospectively collected data from 1,535 couples in the Pregnancy Study Online (PRESTO) study, a preconception cohort study examining risk factors for adverse pregnancy outcomes. PRESTO enrolled women aged 21-45 years and their male partners aged 21 years or older who were attempting to conceive without the use of fertility treatment.

The researchers administered a screening and baseline questionnaire to the women, who then included their male partners in the study. The male partners completed their own baseline questionnaire that asked about demographics, medical history, and lifestyle or behavioral factors including marijuana use. The questions centering around marijuana use asked whether the partner had used marijuana within the past 2 months, and the frequency of marijuana use during that period.

Women in PRESTO were followed every 8 weeks until a pregnancy occurred, or up to 12 months if no pregnancy occurred. If they became pregnant, the women were asked additional questions at less than 12 weeks’ gestation and then again at 32 weeks’ gestation, including questions about any miscarriages, and how long a pregnancy lasted if a miscarriage did occur.

At baseline, 1,267 couples (83%) reported no marijuana use by male partners, 140 couples (9%) reported use less than 1 time per week, and 128 couples (8%) reported marijuana use at least 1 time per week. Men at baseline were similar in age and body mass index among groups, but men who used marijuana were more likely to be cigarette smokers (24% vs. 4%), were more likely to have partners who were cigarette smokers (11% vs. 2%), and were more likely to have partners who use marijuana (43% vs. 3%), compared with couples where the male partners did not use marijuana. Male partners who used marijuana also were less likely to be taking a daily multivitamin (25% vs. 37%), and were more likely to have been diagnosed with anxiety (14% vs. 7%) or depression (20% vs. 9%) compared with male partners who did not use marijuana.

Overall, 269 spontaneous abortions (17.5%) occurred during the study period, and couples where male partners used marijuana one or more times per week had approximately twice the rate of spontaneous abortions, compared with no marijuana use (hazard ratio, 1.99; 95% confidence interval).

Couples in which men who used marijuana less than 1 time per week had a slightly increased risk of spontaneous abortion, but this did not reach statistical significance.

When the results were adjusted for female nonusers of marijuana, the results were “essentially identical,” said Ms. Harlow.

Couples who were trying to conceive for three or fewer cycles at baseline (1,045 couples) had a lower rate of spontaneous abortion than that of couples trying for three or more cycles (490 couples). When the results were stratified by gestational age at loss, the results persisted for couples with a pregnancy loss at less than 8 weeks (1,533 couples), but the effect of marijuana use was reduced for couples with a loss at 8 weeks or more (1,113 couples).

Ms. Harlow noted several limitations to the study, including lack of data on time-varying marijuana use, potential selection bias, and residual confounding. There also is likely misclassification of exposure among some participants because marijuana use was self-reported, she added.

Ms. Harlow reported no relevant conflicts of interest.

SOURCE: Harlow AF et al. ASRM 2019. Abstract O-4.

PHILADELPHIA – When the male partner used marijuana one or more times per week before conception, couples had a higher rate of spontaneous abortion, compared with infrequent use or no use of marijuana by the male partner, Alyssa F. Harlow, MPH, reported at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The male partner’s use of marijuana “one or more times per week in the past 2 months during the preconception period in our study was associated with an increased risk of spontaneous abortion,” said Ms. Harlow, a PhD candidate at Boston University. “The association attenuated for later pregnancy losses, and persisted for those with shorter [pregnancy] attempt time at [study] entry.”

Ms. Harlow and colleagues prospectively collected data from 1,535 couples in the Pregnancy Study Online (PRESTO) study, a preconception cohort study examining risk factors for adverse pregnancy outcomes. PRESTO enrolled women aged 21-45 years and their male partners aged 21 years or older who were attempting to conceive without the use of fertility treatment.

The researchers administered a screening and baseline questionnaire to the women, who then included their male partners in the study. The male partners completed their own baseline questionnaire that asked about demographics, medical history, and lifestyle or behavioral factors including marijuana use. The questions centering around marijuana use asked whether the partner had used marijuana within the past 2 months, and the frequency of marijuana use during that period.

Women in PRESTO were followed every 8 weeks until a pregnancy occurred, or up to 12 months if no pregnancy occurred. If they became pregnant, the women were asked additional questions at less than 12 weeks’ gestation and then again at 32 weeks’ gestation, including questions about any miscarriages, and how long a pregnancy lasted if a miscarriage did occur.

At baseline, 1,267 couples (83%) reported no marijuana use by male partners, 140 couples (9%) reported use less than 1 time per week, and 128 couples (8%) reported marijuana use at least 1 time per week. Men at baseline were similar in age and body mass index among groups, but men who used marijuana were more likely to be cigarette smokers (24% vs. 4%), were more likely to have partners who were cigarette smokers (11% vs. 2%), and were more likely to have partners who use marijuana (43% vs. 3%), compared with couples where the male partners did not use marijuana. Male partners who used marijuana also were less likely to be taking a daily multivitamin (25% vs. 37%), and were more likely to have been diagnosed with anxiety (14% vs. 7%) or depression (20% vs. 9%) compared with male partners who did not use marijuana.

Overall, 269 spontaneous abortions (17.5%) occurred during the study period, and couples where male partners used marijuana one or more times per week had approximately twice the rate of spontaneous abortions, compared with no marijuana use (hazard ratio, 1.99; 95% confidence interval).

Couples in which men who used marijuana less than 1 time per week had a slightly increased risk of spontaneous abortion, but this did not reach statistical significance.

When the results were adjusted for female nonusers of marijuana, the results were “essentially identical,” said Ms. Harlow.

Couples who were trying to conceive for three or fewer cycles at baseline (1,045 couples) had a lower rate of spontaneous abortion than that of couples trying for three or more cycles (490 couples). When the results were stratified by gestational age at loss, the results persisted for couples with a pregnancy loss at less than 8 weeks (1,533 couples), but the effect of marijuana use was reduced for couples with a loss at 8 weeks or more (1,113 couples).

Ms. Harlow noted several limitations to the study, including lack of data on time-varying marijuana use, potential selection bias, and residual confounding. There also is likely misclassification of exposure among some participants because marijuana use was self-reported, she added.

Ms. Harlow reported no relevant conflicts of interest.

SOURCE: Harlow AF et al. ASRM 2019. Abstract O-4.

PHILADELPHIA – When the male partner used marijuana one or more times per week before conception, couples had a higher rate of spontaneous abortion, compared with infrequent use or no use of marijuana by the male partner, Alyssa F. Harlow, MPH, reported at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The male partner’s use of marijuana “one or more times per week in the past 2 months during the preconception period in our study was associated with an increased risk of spontaneous abortion,” said Ms. Harlow, a PhD candidate at Boston University. “The association attenuated for later pregnancy losses, and persisted for those with shorter [pregnancy] attempt time at [study] entry.”

Ms. Harlow and colleagues prospectively collected data from 1,535 couples in the Pregnancy Study Online (PRESTO) study, a preconception cohort study examining risk factors for adverse pregnancy outcomes. PRESTO enrolled women aged 21-45 years and their male partners aged 21 years or older who were attempting to conceive without the use of fertility treatment.

The researchers administered a screening and baseline questionnaire to the women, who then included their male partners in the study. The male partners completed their own baseline questionnaire that asked about demographics, medical history, and lifestyle or behavioral factors including marijuana use. The questions centering around marijuana use asked whether the partner had used marijuana within the past 2 months, and the frequency of marijuana use during that period.

Women in PRESTO were followed every 8 weeks until a pregnancy occurred, or up to 12 months if no pregnancy occurred. If they became pregnant, the women were asked additional questions at less than 12 weeks’ gestation and then again at 32 weeks’ gestation, including questions about any miscarriages, and how long a pregnancy lasted if a miscarriage did occur.

At baseline, 1,267 couples (83%) reported no marijuana use by male partners, 140 couples (9%) reported use less than 1 time per week, and 128 couples (8%) reported marijuana use at least 1 time per week. Men at baseline were similar in age and body mass index among groups, but men who used marijuana were more likely to be cigarette smokers (24% vs. 4%), were more likely to have partners who were cigarette smokers (11% vs. 2%), and were more likely to have partners who use marijuana (43% vs. 3%), compared with couples where the male partners did not use marijuana. Male partners who used marijuana also were less likely to be taking a daily multivitamin (25% vs. 37%), and were more likely to have been diagnosed with anxiety (14% vs. 7%) or depression (20% vs. 9%) compared with male partners who did not use marijuana.

Overall, 269 spontaneous abortions (17.5%) occurred during the study period, and couples where male partners used marijuana one or more times per week had approximately twice the rate of spontaneous abortions, compared with no marijuana use (hazard ratio, 1.99; 95% confidence interval).

Couples in which men who used marijuana less than 1 time per week had a slightly increased risk of spontaneous abortion, but this did not reach statistical significance.

When the results were adjusted for female nonusers of marijuana, the results were “essentially identical,” said Ms. Harlow.

Couples who were trying to conceive for three or fewer cycles at baseline (1,045 couples) had a lower rate of spontaneous abortion than that of couples trying for three or more cycles (490 couples). When the results were stratified by gestational age at loss, the results persisted for couples with a pregnancy loss at less than 8 weeks (1,533 couples), but the effect of marijuana use was reduced for couples with a loss at 8 weeks or more (1,113 couples).

Ms. Harlow noted several limitations to the study, including lack of data on time-varying marijuana use, potential selection bias, and residual confounding. There also is likely misclassification of exposure among some participants because marijuana use was self-reported, she added.

Ms. Harlow reported no relevant conflicts of interest.

SOURCE: Harlow AF et al. ASRM 2019. Abstract O-4.

PHILADELPHIA – Women with obesity who underwent a lifestyle program targeting healthy eating and physical activity were significantly more likely to achieve pregnancy or become spontaneously pregnant, Jean-Patrice Baillargeon, MD, MSc, reported at the annual meeting of the American Society for Reproductive Medicine.

World Obesity Federation

However, women with polycystic ovary syndrome (PCOS) in the study appeared to benefit more than did women without PCOS who participated in the lifestyle program, said Dr. Baillargeon, from the University of Sherbrooke (Que.).

“Our lifestyle program targeting women with obesity seeking fertility treatments increased the chances of conceiving, mainly spontaneously. Women with PCOS seemed to benefit more from such a program,” said Dr. Baillargeon.

“These benefits occur along with small changes in weight, but important improvements in lifestyle, so lifestyle seems to be more important than weight change here,” he added.

The researchers randomized 130 women to receive the Fit-For-Fertility lifestyle program or usual care for infertility. The lifestyle program consisted of a low-intensity weekly intervention for 6 weeks in which patients met individually with a kinesiologist and nutritionist every week and also attended group sessions each week. Women in the intervention did not receive fertility treatment for the first 6 months while on the lifestyle program, and if they did not conceive during that time, they continued the program in combination with fertility treatments.

Patients were included if they were aged 18-40 years and had either infertility and a body mass index of 30 kg/m² or greater or PCOS and a BMI of 27 kg/m² or greater. Researchers excluded women planning to undergo bariatric surgery, women who were already undergoing another lifestyle intervention, and women with severe infertility or who had a male partner with severe infertility for whom in vitro fertilization was their only option for conceiving. Researchers collected data from patients at baseline and every 6 months up to 18 months, with additional visits for pregnant women scheduled at the beginning of pregnancy and at 26 weeks’ gestation. They collected baseline data on age, BMI, waist circumference, fat mass percentage, daily energy expenditure, and food frequency using the Healthy Eating Index (HEI).

Overall, 46 women in the intervention group and 52 women in the control group had a research visit at 6 months or pregnancy research visit at less than 6 months; of these, 33 women in the intervention group (65%) and 35 women in the control group (61%) had PCOS. At baseline, both PCOS and non-PCOS groups were similar; however, women in the PCOS intervention group had a lower BMI than did women without PCOS in the intervention group (37 kg/m² vs. 41 kg/m²; P less than .05), while women without PCOS in the intervention group had a higher fat mass percentage than did women with PCOS in the intervention group (46% vs. 49%; P less than .05).

With regard to weight loss, there was a 2.4% reduction in weight among all patients in the intervention group, compared with the control group (P = .003), with a 2.7% reduction in weight for the PCOS group (P = .015) and a 1.8% reduction in the non-PCOS group (P = .139). However, there were no significant differences between PCOS status and the lifestyle intervention, said Dr. Baillargeon.

At 6 months, the quality of women’s diets in the combined PCOS and non-PCOS group that participated in the lifestyle program showed significant improvement, compared with control groups (HEI, 18% vs. 5%; P less than .001). The PCOS group on its own showed significant improvement with the intervention (20% vs. 4%; P less than .001), whereas women without PCOS showed a nonsignificant improvement with the intervention (14% vs. 6%; P = .055). Daily energy expenditure improved in all groups that received the intervention, compared with the control groups, but there were no significant between-group differences in energy expenditure.

When analyzing fertility outcomes at 18 months, the pregnancy rate for all patients who received lifestyle interventions was 61%, compared with 39% in the control group (P = .02; number needed to treat, 4.5). In women with PCOS, those who underwent the lifestyle intervention had a pregnancy rate of 58%, compared with 34% in the control group (P = .05; NNT, 4.3); although women without PCOS who participated in the lifestyle program had an improved pregnancy rate over women in the control group, the results were not significant (67% vs. 46%; P = .18; NNT, 4.7).

The researchers also looked at the spontaneous pregnancy rate and found women who received the intervention had nearly three times the rate of spontaneous pregnancy, compared with women in the control group (33% vs. 12%; P = .01), while women with PCOS in the lifestyle program had nearly five times the rate of spontaneous pregnancy, compared with the control group (27% vs. 6%; P = .02). Women without PCOS in the lifestyle program had nearly twice the increased likelihood of spontaneous pregnancy, but the results were not significant (44% vs. 23%; P = .15).

Women with PCOS in the lifestyle program also had a higher live birth rate, compared with women in the control group (55% vs. 31%; P = .05; NNT, 4.3). Although women without PCOS in the lifestyle program (67% vs. 46%; P = .18; NNT, 4.7) and women in the study overall experienced higher live birth rates (51% vs. 37%; P = .14; NNT, 7.0), compared with the control group, these results were not significant, said Dr. Baillargeon.

“Such lifestyle interventions in women with obesity could significantly lower costs of fertility treatments, which is important,” concluded Dr. Baillargeon.

The Fit-For-Fertility program was funded by an unrestricted grant from Ferring.

SOURCE: Baillargeon J-P, et al. ASRM 2019. Abstract O-95.

PHILADELPHIA – Women with obesity who underwent a lifestyle program targeting healthy eating and physical activity were significantly more likely to achieve pregnancy or become spontaneously pregnant, Jean-Patrice Baillargeon, MD, MSc, reported at the annual meeting of the American Society for Reproductive Medicine.

World Obesity Federation

However, women with polycystic ovary syndrome (PCOS) in the study appeared to benefit more than did women without PCOS who participated in the lifestyle program, said Dr. Baillargeon, from the University of Sherbrooke (Que.).

“Our lifestyle program targeting women with obesity seeking fertility treatments increased the chances of conceiving, mainly spontaneously. Women with PCOS seemed to benefit more from such a program,” said Dr. Baillargeon.

“These benefits occur along with small changes in weight, but important improvements in lifestyle, so lifestyle seems to be more important than weight change here,” he added.

The researchers randomized 130 women to receive the Fit-For-Fertility lifestyle program or usual care for infertility. The lifestyle program consisted of a low-intensity weekly intervention for 6 weeks in which patients met individually with a kinesiologist and nutritionist every week and also attended group sessions each week. Women in the intervention did not receive fertility treatment for the first 6 months while on the lifestyle program, and if they did not conceive during that time, they continued the program in combination with fertility treatments.

Patients were included if they were aged 18-40 years and had either infertility and a body mass index of 30 kg/m² or greater or PCOS and a BMI of 27 kg/m² or greater. Researchers excluded women planning to undergo bariatric surgery, women who were already undergoing another lifestyle intervention, and women with severe infertility or who had a male partner with severe infertility for whom in vitro fertilization was their only option for conceiving. Researchers collected data from patients at baseline and every 6 months up to 18 months, with additional visits for pregnant women scheduled at the beginning of pregnancy and at 26 weeks’ gestation. They collected baseline data on age, BMI, waist circumference, fat mass percentage, daily energy expenditure, and food frequency using the Healthy Eating Index (HEI).

Overall, 46 women in the intervention group and 52 women in the control group had a research visit at 6 months or pregnancy research visit at less than 6 months; of these, 33 women in the intervention group (65%) and 35 women in the control group (61%) had PCOS. At baseline, both PCOS and non-PCOS groups were similar; however, women in the PCOS intervention group had a lower BMI than did women without PCOS in the intervention group (37 kg/m² vs. 41 kg/m²; P less than .05), while women without PCOS in the intervention group had a higher fat mass percentage than did women with PCOS in the intervention group (46% vs. 49%; P less than .05).

With regard to weight loss, there was a 2.4% reduction in weight among all patients in the intervention group, compared with the control group (P = .003), with a 2.7% reduction in weight for the PCOS group (P = .015) and a 1.8% reduction in the non-PCOS group (P = .139). However, there were no significant differences between PCOS status and the lifestyle intervention, said Dr. Baillargeon.

At 6 months, the quality of women’s diets in the combined PCOS and non-PCOS group that participated in the lifestyle program showed significant improvement, compared with control groups (HEI, 18% vs. 5%; P less than .001). The PCOS group on its own showed significant improvement with the intervention (20% vs. 4%; P less than .001), whereas women without PCOS showed a nonsignificant improvement with the intervention (14% vs. 6%; P = .055). Daily energy expenditure improved in all groups that received the intervention, compared with the control groups, but there were no significant between-group differences in energy expenditure.

When analyzing fertility outcomes at 18 months, the pregnancy rate for all patients who received lifestyle interventions was 61%, compared with 39% in the control group (P = .02; number needed to treat, 4.5). In women with PCOS, those who underwent the lifestyle intervention had a pregnancy rate of 58%, compared with 34% in the control group (P = .05; NNT, 4.3); although women without PCOS who participated in the lifestyle program had an improved pregnancy rate over women in the control group, the results were not significant (67% vs. 46%; P = .18; NNT, 4.7).

The researchers also looked at the spontaneous pregnancy rate and found women who received the intervention had nearly three times the rate of spontaneous pregnancy, compared with women in the control group (33% vs. 12%; P = .01), while women with PCOS in the lifestyle program had nearly five times the rate of spontaneous pregnancy, compared with the control group (27% vs. 6%; P = .02). Women without PCOS in the lifestyle program had nearly twice the increased likelihood of spontaneous pregnancy, but the results were not significant (44% vs. 23%; P = .15).

Women with PCOS in the lifestyle program also had a higher live birth rate, compared with women in the control group (55% vs. 31%; P = .05; NNT, 4.3). Although women without PCOS in the lifestyle program (67% vs. 46%; P = .18; NNT, 4.7) and women in the study overall experienced higher live birth rates (51% vs. 37%; P = .14; NNT, 7.0), compared with the control group, these results were not significant, said Dr. Baillargeon.

“Such lifestyle interventions in women with obesity could significantly lower costs of fertility treatments, which is important,” concluded Dr. Baillargeon.

The Fit-For-Fertility program was funded by an unrestricted grant from Ferring.

SOURCE: Baillargeon J-P, et al. ASRM 2019. Abstract O-95.

PHILADELPHIA – Women with obesity who underwent a lifestyle program targeting healthy eating and physical activity were significantly more likely to achieve pregnancy or become spontaneously pregnant, Jean-Patrice Baillargeon, MD, MSc, reported at the annual meeting of the American Society for Reproductive Medicine.

World Obesity Federation

However, women with polycystic ovary syndrome (PCOS) in the study appeared to benefit more than did women without PCOS who participated in the lifestyle program, said Dr. Baillargeon, from the University of Sherbrooke (Que.).

“Our lifestyle program targeting women with obesity seeking fertility treatments increased the chances of conceiving, mainly spontaneously. Women with PCOS seemed to benefit more from such a program,” said Dr. Baillargeon.

“These benefits occur along with small changes in weight, but important improvements in lifestyle, so lifestyle seems to be more important than weight change here,” he added.

The researchers randomized 130 women to receive the Fit-For-Fertility lifestyle program or usual care for infertility. The lifestyle program consisted of a low-intensity weekly intervention for 6 weeks in which patients met individually with a kinesiologist and nutritionist every week and also attended group sessions each week. Women in the intervention did not receive fertility treatment for the first 6 months while on the lifestyle program, and if they did not conceive during that time, they continued the program in combination with fertility treatments.

Patients were included if they were aged 18-40 years and had either infertility and a body mass index of 30 kg/m² or greater or PCOS and a BMI of 27 kg/m² or greater. Researchers excluded women planning to undergo bariatric surgery, women who were already undergoing another lifestyle intervention, and women with severe infertility or who had a male partner with severe infertility for whom in vitro fertilization was their only option for conceiving. Researchers collected data from patients at baseline and every 6 months up to 18 months, with additional visits for pregnant women scheduled at the beginning of pregnancy and at 26 weeks’ gestation. They collected baseline data on age, BMI, waist circumference, fat mass percentage, daily energy expenditure, and food frequency using the Healthy Eating Index (HEI).

Overall, 46 women in the intervention group and 52 women in the control group had a research visit at 6 months or pregnancy research visit at less than 6 months; of these, 33 women in the intervention group (65%) and 35 women in the control group (61%) had PCOS. At baseline, both PCOS and non-PCOS groups were similar; however, women in the PCOS intervention group had a lower BMI than did women without PCOS in the intervention group (37 kg/m² vs. 41 kg/m²; P less than .05), while women without PCOS in the intervention group had a higher fat mass percentage than did women with PCOS in the intervention group (46% vs. 49%; P less than .05).

With regard to weight loss, there was a 2.4% reduction in weight among all patients in the intervention group, compared with the control group (P = .003), with a 2.7% reduction in weight for the PCOS group (P = .015) and a 1.8% reduction in the non-PCOS group (P = .139). However, there were no significant differences between PCOS status and the lifestyle intervention, said Dr. Baillargeon.

At 6 months, the quality of women’s diets in the combined PCOS and non-PCOS group that participated in the lifestyle program showed significant improvement, compared with control groups (HEI, 18% vs. 5%; P less than .001). The PCOS group on its own showed significant improvement with the intervention (20% vs. 4%; P less than .001), whereas women without PCOS showed a nonsignificant improvement with the intervention (14% vs. 6%; P = .055). Daily energy expenditure improved in all groups that received the intervention, compared with the control groups, but there were no significant between-group differences in energy expenditure.

When analyzing fertility outcomes at 18 months, the pregnancy rate for all patients who received lifestyle interventions was 61%, compared with 39% in the control group (P = .02; number needed to treat, 4.5). In women with PCOS, those who underwent the lifestyle intervention had a pregnancy rate of 58%, compared with 34% in the control group (P = .05; NNT, 4.3); although women without PCOS who participated in the lifestyle program had an improved pregnancy rate over women in the control group, the results were not significant (67% vs. 46%; P = .18; NNT, 4.7).

The researchers also looked at the spontaneous pregnancy rate and found women who received the intervention had nearly three times the rate of spontaneous pregnancy, compared with women in the control group (33% vs. 12%; P = .01), while women with PCOS in the lifestyle program had nearly five times the rate of spontaneous pregnancy, compared with the control group (27% vs. 6%; P = .02). Women without PCOS in the lifestyle program had nearly twice the increased likelihood of spontaneous pregnancy, but the results were not significant (44% vs. 23%; P = .15).

Women with PCOS in the lifestyle program also had a higher live birth rate, compared with women in the control group (55% vs. 31%; P = .05; NNT, 4.3). Although women without PCOS in the lifestyle program (67% vs. 46%; P = .18; NNT, 4.7) and women in the study overall experienced higher live birth rates (51% vs. 37%; P = .14; NNT, 7.0), compared with the control group, these results were not significant, said Dr. Baillargeon.

“Such lifestyle interventions in women with obesity could significantly lower costs of fertility treatments, which is important,” concluded Dr. Baillargeon.

The Fit-For-Fertility program was funded by an unrestricted grant from Ferring.

SOURCE: Baillargeon J-P, et al. ASRM 2019. Abstract O-95.

Patients with chronic obstructive pulmonary disease who received opioids or benzodiazepines had a greater risk of hospitalization for respiratory-related adverse events, according to recent research from Annals of the American Thoracic Society.

sdominick/Getty Images

In addition, the risk of hospitalization because of respiratory events for patients with chronic obstructive pulmonary disease (COPD) was greater when opioid and benzodiazepine medications were combined, compared with patients who did not take either medication, Jacques G. Baillargeon, PhD, of the department of preventive medicine and community health at the University of Texas, Galveston, and colleagues wrote.

“Patients with COPD and their physicians should judiciously assess the risks and benefits of opioids and benzodiazepines, alone and in combination, and preferentially recommend nonopioid and nonbenzodiazepine approaches for pain, sleep, and anxiety management in patients with COPD,” the investigators wrote.

The researchers performed a case-control study of 3,232 Medicare beneficiary cases of COPD patients who were aged at least 66 years. Patients were included if they experienced a hospitalization related to a COPD-related adverse event with a respiratory diagnosis in 2014 and then matched to one or two control patients (total, 6,247 patients) based on age at hospitalization, gender, COPD medication, COPD complexity, obstructive sleep apnea, and socioeconomic status. COPD complexity was assigned to three levels (low, moderate, high) and calculated using the patient’s comorbid respiratory conditions and associated medical procedures in the 12 months prior to their hospitalization.

They found that, in the 30 days before COPD-related hospitalization, use of opioids was associated with greater likelihood of hospitalization (adjusted odds ratio, 1.73; 95% confidence interval, 1.52-1.97), as was use of benzodiazepines (aOR, 1.42; 95% CI, 1.21-1.66). When patients used both opioids and benzodiazepines, they had a significantly higher risk of hospitalization, compared with patients who did not use opioids or benzodiazepines (aOR, 2.32; 95% CI, 1.94-2.77).

In the 60 days prior to hospitalization, there was also a greater likelihood of hospitalization among COPD patients who used opioids (aOR, 1.66; 95% CI, 1.47-1.88), benzodiazepines (aOR, 1.44; 95% CI, 1.24-1.67), and both opioids and benzodiazepines (aOR, 2.27; 95% CI, 1.93-2.67); at 90 days, this higher risk of hospitalization persisted among COPD patients taking opioids (aOR, 1.58; 95% CI, 1.40-1.78), benzodiazepines (aOR, 1.40; 95% CI, 1.20-1.63), and both opioids and benzodiazepines (aOR, 2.21; 95% CI, 1.88-2.59).

The researchers acknowledged that one potential limitation in the study was how COPD diagnoses were obtained through coding performed by clinicians instead of from laboratory testing. Confounding by COPD indication and severity; use of over-the-counter medication or opioids and benzodiazepines received illegally; and lack of analyses of potential confounders such as diet, alcohol use, smoking status and herbal supplement use were other limitations.

This study was supported by an award from the National Center for Advancing Translational Sciences and National Institutes of Health. Dr. Baillargeon had no disclosures.

SOURCE: Baillargeon JG et al. Ann Am Thorac Soc. 2019 Oct 1. doi: 10.1513/AnnalsATS.201901-024OC.

Patients with chronic obstructive pulmonary disease who received opioids or benzodiazepines had a greater risk of hospitalization for respiratory-related adverse events, according to recent research from Annals of the American Thoracic Society.

sdominick/Getty Images

In addition, the risk of hospitalization because of respiratory events for patients with chronic obstructive pulmonary disease (COPD) was greater when opioid and benzodiazepine medications were combined, compared with patients who did not take either medication, Jacques G. Baillargeon, PhD, of the department of preventive medicine and community health at the University of Texas, Galveston, and colleagues wrote.

“Patients with COPD and their physicians should judiciously assess the risks and benefits of opioids and benzodiazepines, alone and in combination, and preferentially recommend nonopioid and nonbenzodiazepine approaches for pain, sleep, and anxiety management in patients with COPD,” the investigators wrote.

The researchers performed a case-control study of 3,232 Medicare beneficiary cases of COPD patients who were aged at least 66 years. Patients were included if they experienced a hospitalization related to a COPD-related adverse event with a respiratory diagnosis in 2014 and then matched to one or two control patients (total, 6,247 patients) based on age at hospitalization, gender, COPD medication, COPD complexity, obstructive sleep apnea, and socioeconomic status. COPD complexity was assigned to three levels (low, moderate, high) and calculated using the patient’s comorbid respiratory conditions and associated medical procedures in the 12 months prior to their hospitalization.

They found that, in the 30 days before COPD-related hospitalization, use of opioids was associated with greater likelihood of hospitalization (adjusted odds ratio, 1.73; 95% confidence interval, 1.52-1.97), as was use of benzodiazepines (aOR, 1.42; 95% CI, 1.21-1.66). When patients used both opioids and benzodiazepines, they had a significantly higher risk of hospitalization, compared with patients who did not use opioids or benzodiazepines (aOR, 2.32; 95% CI, 1.94-2.77).

In the 60 days prior to hospitalization, there was also a greater likelihood of hospitalization among COPD patients who used opioids (aOR, 1.66; 95% CI, 1.47-1.88), benzodiazepines (aOR, 1.44; 95% CI, 1.24-1.67), and both opioids and benzodiazepines (aOR, 2.27; 95% CI, 1.93-2.67); at 90 days, this higher risk of hospitalization persisted among COPD patients taking opioids (aOR, 1.58; 95% CI, 1.40-1.78), benzodiazepines (aOR, 1.40; 95% CI, 1.20-1.63), and both opioids and benzodiazepines (aOR, 2.21; 95% CI, 1.88-2.59).

The researchers acknowledged that one potential limitation in the study was how COPD diagnoses were obtained through coding performed by clinicians instead of from laboratory testing. Confounding by COPD indication and severity; use of over-the-counter medication or opioids and benzodiazepines received illegally; and lack of analyses of potential confounders such as diet, alcohol use, smoking status and herbal supplement use were other limitations.

This study was supported by an award from the National Center for Advancing Translational Sciences and National Institutes of Health. Dr. Baillargeon had no disclosures.

SOURCE: Baillargeon JG et al. Ann Am Thorac Soc. 2019 Oct 1. doi: 10.1513/AnnalsATS.201901-024OC.

Patients with chronic obstructive pulmonary disease who received opioids or benzodiazepines had a greater risk of hospitalization for respiratory-related adverse events, according to recent research from Annals of the American Thoracic Society.

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In addition, the risk of hospitalization because of respiratory events for patients with chronic obstructive pulmonary disease (COPD) was greater when opioid and benzodiazepine medications were combined, compared with patients who did not take either medication, Jacques G. Baillargeon, PhD, of the department of preventive medicine and community health at the University of Texas, Galveston, and colleagues wrote.

“Patients with COPD and their physicians should judiciously assess the risks and benefits of opioids and benzodiazepines, alone and in combination, and preferentially recommend nonopioid and nonbenzodiazepine approaches for pain, sleep, and anxiety management in patients with COPD,” the investigators wrote.

The researchers performed a case-control study of 3,232 Medicare beneficiary cases of COPD patients who were aged at least 66 years. Patients were included if they experienced a hospitalization related to a COPD-related adverse event with a respiratory diagnosis in 2014 and then matched to one or two control patients (total, 6,247 patients) based on age at hospitalization, gender, COPD medication, COPD complexity, obstructive sleep apnea, and socioeconomic status. COPD complexity was assigned to three levels (low, moderate, high) and calculated using the patient’s comorbid respiratory conditions and associated medical procedures in the 12 months prior to their hospitalization.

They found that, in the 30 days before COPD-related hospitalization, use of opioids was associated with greater likelihood of hospitalization (adjusted odds ratio, 1.73; 95% confidence interval, 1.52-1.97), as was use of benzodiazepines (aOR, 1.42; 95% CI, 1.21-1.66). When patients used both opioids and benzodiazepines, they had a significantly higher risk of hospitalization, compared with patients who did not use opioids or benzodiazepines (aOR, 2.32; 95% CI, 1.94-2.77).

In the 60 days prior to hospitalization, there was also a greater likelihood of hospitalization among COPD patients who used opioids (aOR, 1.66; 95% CI, 1.47-1.88), benzodiazepines (aOR, 1.44; 95% CI, 1.24-1.67), and both opioids and benzodiazepines (aOR, 2.27; 95% CI, 1.93-2.67); at 90 days, this higher risk of hospitalization persisted among COPD patients taking opioids (aOR, 1.58; 95% CI, 1.40-1.78), benzodiazepines (aOR, 1.40; 95% CI, 1.20-1.63), and both opioids and benzodiazepines (aOR, 2.21; 95% CI, 1.88-2.59).

The researchers acknowledged that one potential limitation in the study was how COPD diagnoses were obtained through coding performed by clinicians instead of from laboratory testing. Confounding by COPD indication and severity; use of over-the-counter medication or opioids and benzodiazepines received illegally; and lack of analyses of potential confounders such as diet, alcohol use, smoking status and herbal supplement use were other limitations.

This study was supported by an award from the National Center for Advancing Translational Sciences and National Institutes of Health. Dr. Baillargeon had no disclosures.

SOURCE: Baillargeon JG et al. Ann Am Thorac Soc. 2019 Oct 1. doi: 10.1513/AnnalsATS.201901-024OC.

Patients with moderate to severe atopic dermatitis who received the immunoglobulin G1 anti–interleukin-33 monoclonal antibody etokimab showed significant disease improvement 29 days after receiving a single systemic administration, according to results from a recent proof-of-concept, phase IIa study.

“Most of the focus for IL-33 pathway inhibition has been on the type 2 cytokine axis because of significant supporting genetic and functional data in both human and murine systems,” Yi-Ling Chen, a DPhil student at the University of Oxford (England), and colleagues wrote in Science Translational Medicine. “Our findings might also provide a further dimension to explain how etokimab, by inhibiting IL-33, could provide such a rapid and persistent clinical benefit as described in this report.”

In their study, 12 patients with moderate to severe AD received etokimab in a single intravenous dose of 300 mg. Prior to receiving etokimab, patients received a placebo dose and then underwent saline or house dust mite intraepidermal challenge, with researchers obtaining blister samples 1 day after challenge following placebo administration and again after patients received etokimab.

At 29 days, 83% of patients reached rapid and sustained clinical benefit under Eczema Area and Severity Index (EASI ) 50 and 33% in EASI 75, including peripheral eosinophil reduction. There also was significant reduction in skin neutrophil infiltration after patients received etokimab and then house dust mite challenge, compared with after they received placebo, .

“These findings open new therapeutic possible applications of etokimab to sterile neutrophilic disease as well as other inflammatory diseases with a clear neutrophilic involvement such as neutrophilic asthma,” the researchers said. “This first-in-class experimental medicine study has shown that in vivo in human tissue IL-33 has key upstream effects which broadly influence different and relevant inflammatory cascades and thus widen the potential of this treatment to a larger than anticipated group of diseases.

“Although excellent previous studies have demonstrated in vitro and in murine models that IL-33 is involved in neutrophil migration, the translation here to human tissue immunology shows that IL-33 plays a dominant role and effects are in part likely to be mediated instead by CXCR1,” concluded Ms. Chen and colleagues. “Therefore, specific IL-33 therapeutic intervention is not targeting a redundant system and is worthy of further investigation.”

This study was funded by AnaptysBio, which was responsible for the conception and design of the study. AnaptysBio also helped in part to analyze and interpret the data from the study, and approved it for submission. Dr. Ogg reported having served on an advisory board, as a consultant, or holds equity in Eli Lilly, Novartis, Janssen, Orbit Discovery, and UCB Pharma. Ms. Marquette and Dr. Londei reported being employees of AnaptysBio.

SOURCE: Chen Y-L et al. Sci Transl Med. 2019. doi: 10.1126/scitranslmed.aax2945.

Patients with moderate to severe atopic dermatitis who received the immunoglobulin G1 anti–interleukin-33 monoclonal antibody etokimab showed significant disease improvement 29 days after receiving a single systemic administration, according to results from a recent proof-of-concept, phase IIa study.

“Most of the focus for IL-33 pathway inhibition has been on the type 2 cytokine axis because of significant supporting genetic and functional data in both human and murine systems,” Yi-Ling Chen, a DPhil student at the University of Oxford (England), and colleagues wrote in Science Translational Medicine. “Our findings might also provide a further dimension to explain how etokimab, by inhibiting IL-33, could provide such a rapid and persistent clinical benefit as described in this report.”

In their study, 12 patients with moderate to severe AD received etokimab in a single intravenous dose of 300 mg. Prior to receiving etokimab, patients received a placebo dose and then underwent saline or house dust mite intraepidermal challenge, with researchers obtaining blister samples 1 day after challenge following placebo administration and again after patients received etokimab.

At 29 days, 83% of patients reached rapid and sustained clinical benefit under Eczema Area and Severity Index (EASI ) 50 and 33% in EASI 75, including peripheral eosinophil reduction. There also was significant reduction in skin neutrophil infiltration after patients received etokimab and then house dust mite challenge, compared with after they received placebo, .

“These findings open new therapeutic possible applications of etokimab to sterile neutrophilic disease as well as other inflammatory diseases with a clear neutrophilic involvement such as neutrophilic asthma,” the researchers said. “This first-in-class experimental medicine study has shown that in vivo in human tissue IL-33 has key upstream effects which broadly influence different and relevant inflammatory cascades and thus widen the potential of this treatment to a larger than anticipated group of diseases.

“Although excellent previous studies have demonstrated in vitro and in murine models that IL-33 is involved in neutrophil migration, the translation here to human tissue immunology shows that IL-33 plays a dominant role and effects are in part likely to be mediated instead by CXCR1,” concluded Ms. Chen and colleagues. “Therefore, specific IL-33 therapeutic intervention is not targeting a redundant system and is worthy of further investigation.”

This study was funded by AnaptysBio, which was responsible for the conception and design of the study. AnaptysBio also helped in part to analyze and interpret the data from the study, and approved it for submission. Dr. Ogg reported having served on an advisory board, as a consultant, or holds equity in Eli Lilly, Novartis, Janssen, Orbit Discovery, and UCB Pharma. Ms. Marquette and Dr. Londei reported being employees of AnaptysBio.

SOURCE: Chen Y-L et al. Sci Transl Med. 2019. doi: 10.1126/scitranslmed.aax2945.

Patients with moderate to severe atopic dermatitis who received the immunoglobulin G1 anti–interleukin-33 monoclonal antibody etokimab showed significant disease improvement 29 days after receiving a single systemic administration, according to results from a recent proof-of-concept, phase IIa study.

“Most of the focus for IL-33 pathway inhibition has been on the type 2 cytokine axis because of significant supporting genetic and functional data in both human and murine systems,” Yi-Ling Chen, a DPhil student at the University of Oxford (England), and colleagues wrote in Science Translational Medicine. “Our findings might also provide a further dimension to explain how etokimab, by inhibiting IL-33, could provide such a rapid and persistent clinical benefit as described in this report.”

In their study, 12 patients with moderate to severe AD received etokimab in a single intravenous dose of 300 mg. Prior to receiving etokimab, patients received a placebo dose and then underwent saline or house dust mite intraepidermal challenge, with researchers obtaining blister samples 1 day after challenge following placebo administration and again after patients received etokimab.

At 29 days, 83% of patients reached rapid and sustained clinical benefit under Eczema Area and Severity Index (EASI ) 50 and 33% in EASI 75, including peripheral eosinophil reduction. There also was significant reduction in skin neutrophil infiltration after patients received etokimab and then house dust mite challenge, compared with after they received placebo, .

“These findings open new therapeutic possible applications of etokimab to sterile neutrophilic disease as well as other inflammatory diseases with a clear neutrophilic involvement such as neutrophilic asthma,” the researchers said. “This first-in-class experimental medicine study has shown that in vivo in human tissue IL-33 has key upstream effects which broadly influence different and relevant inflammatory cascades and thus widen the potential of this treatment to a larger than anticipated group of diseases.

“Although excellent previous studies have demonstrated in vitro and in murine models that IL-33 is involved in neutrophil migration, the translation here to human tissue immunology shows that IL-33 plays a dominant role and effects are in part likely to be mediated instead by CXCR1,” concluded Ms. Chen and colleagues. “Therefore, specific IL-33 therapeutic intervention is not targeting a redundant system and is worthy of further investigation.”

This study was funded by AnaptysBio, which was responsible for the conception and design of the study. AnaptysBio also helped in part to analyze and interpret the data from the study, and approved it for submission. Dr. Ogg reported having served on an advisory board, as a consultant, or holds equity in Eli Lilly, Novartis, Janssen, Orbit Discovery, and UCB Pharma. Ms. Marquette and Dr. Londei reported being employees of AnaptysBio.

SOURCE: Chen Y-L et al. Sci Transl Med. 2019. doi: 10.1126/scitranslmed.aax2945.

ORLANDO – Transwomen are more likely to have a lower bone mineral density (BMD) before beginning hormone therapy, compared with male reference populations, but there are no short- or long-term risks to bone health over the life of a transperson who receives hormone therapy, according to a presentation at the annual meeting of the American Society for Bone and Mineral Research.

“Hormonal treatment of transgender people is safe with respect to bone,” said Martin den Heijer, MD, PhD, of the VU University Medical Center in Amsterdam.

At baseline, transwomen have lower bone mass than do male reference populations, said Dr. den Heijer, citing a study that found 25 transwomen had less muscle mass (P less than or equal to .001), strength (P less than or equal to .05), and lower BMD at the hip, femoral neck, and spine (P less than .001), compared with 25 cisgender men in a control group and 941 men in a male reference population (Bone. 2013;54[1]:92-7). In a 2019 study from his own group, Dr. den Heijer said the z score in the lumbar spine for 711 transwomen was -0.9 and the incidence of osteoporosis was 14.2%, compared with a z score of 0.0 and 2.4% incidence of osteoporosis in 543 transmen (J Bone Min Res. 2019;34[3]:447-54).

In the prospective European Network for the Investigation of Gender Incongruence (ENIGI) study, researchers examined short-term effects of hormone therapy on BMD in 144 transwomen and 162 transmen who had a normal body mass index and were mostly white. The percentage of patients who reported they were current smokers was between 25% and 30%, and fewer than 10% said they consumed more than seven units of alcohol per week. Transwomen received estradiol (an oral estradiol valerate at a dose of 4 mg/day or an estradiol patch) together with 100 mg/day of cyproterone acetate, and transmen received testosterone in the form of a gel (50 mg/day), intramuscular esters (250 mg every 2-3 weeks), or intramuscular undecanoate at a dose of 1,000 mg every 12 weeks (J Sex Med. 2016;13[6]:994-9).

After 1 year of treatment, there were significant increases in BMD in transwomen in the lumbar spine (3.67%; 95% confidence interval, 3.20%-4.13%), femoral neck (1.86%; 95% CI, 1.41%-2.31%), and total hip (0.97%; 95% CI, 0.62%-1.31%). Transmen also had increased BMD in the lumbar spine (0.86%; 95% CI, 0.38%-1.35%) and total hip (1.04%; 95% CI, 0.64%-1.44%), with a slight decrease in femoral neck BMD (–0.46%; 95% CI, –1.07% to 0.16%).

Dr. den Heijer also discussed the long-term effects of hormone therapy on BMD in the Amsterdam Cohort of Dysphoria (ACOG) study, which consisted of 711 transwomen and 543 transmen and followed some patients out to 2 years, 5 years, and 10 years after beginning hormone therapy (J Sex Med. 2018;15[4]:582-90). Among transwomen, the median age was 33 years, 68.9% had begun hormone therapy, and 75.3% received a gonadectomy; among transmen, the median age was 25 years, 72.9% had begun hormone therapy, and 83.8% received a gonadectomy. Of these patients, dual-energy x-ray absorptiometry data were available for the lumbar spine BMD for 234 transwomen and 236 transmen at 2 years, 174 transwomen and 95 transmen at 5 years, and 102 transwomen and 70 transmen at 10 years.

Although there was no significant mean change in absolute BMD over the 10-year period, the concentration of estradiol in transwomen and transmen affected change in BMD the longer the transperson was receiving hormone therapy: Transwomen who received an estradiol concentration of 118 pmol/L had a decrease of –0.026% at 2 years, –0.044% at 5 years, and –0.009% at 10 years, compared with a dose of 443 pmol/L (+0.044% at 2 years, +0.025% at 5 years, +0.063% at 10 years), whereas transmen also had decreased BMD at the lowest estradiol concentrations of 95 pmol/L (–0.007% at 2 years, –0.024% at 5 years, +0.010% at 10 years), compared with transmen receiving the highest doses of 323 pmol/L (+0.028% at 2 years, +0.002% at 5 years, +0.053% at 10 years). There was no significant change in BMD in either group at any time point with regard to testosterone concentration.

When the investigators linked these patients to a national statistics database in the Netherlands to evaluate fracture incidence (J Bone Miner Res. 2019 Sep 5. doi: 10.1002/jbmr.3862), pairing five cisgender female controls and five cisgender male controls to every transgender patient, the researchers found transwomen had a higher incidence of osteoporotic fracture of the hip, spine, forearm, and humerus (41.8%), compared with cisgender men (26.6%; P = .014) and cisgender women (36.0%; P = .381). There was not enough information in the study to examine fracture information for transmen, Dr. den Heijer said. Transwomen and transmen who experienced a fracture were more likely to be a current smoker and have lower estradiol concentrations than were transwomen and transmen, respectively, who did not have a fracture.

“Attention for lifestyle factors remains important, especially smoking cessation, vitamin D intake, and regular exercise,” Dr. den Heijer said. “It remains important for everybody, but especially for transgender women.”

Dr. den Heijer reported no relevant conflicts of interest.
 

ORLANDO – Transwomen are more likely to have a lower bone mineral density (BMD) before beginning hormone therapy, compared with male reference populations, but there are no short- or long-term risks to bone health over the life of a transperson who receives hormone therapy, according to a presentation at the annual meeting of the American Society for Bone and Mineral Research.

“Hormonal treatment of transgender people is safe with respect to bone,” said Martin den Heijer, MD, PhD, of the VU University Medical Center in Amsterdam.

At baseline, transwomen have lower bone mass than do male reference populations, said Dr. den Heijer, citing a study that found 25 transwomen had less muscle mass (P less than or equal to .001), strength (P less than or equal to .05), and lower BMD at the hip, femoral neck, and spine (P less than .001), compared with 25 cisgender men in a control group and 941 men in a male reference population (Bone. 2013;54[1]:92-7). In a 2019 study from his own group, Dr. den Heijer said the z score in the lumbar spine for 711 transwomen was -0.9 and the incidence of osteoporosis was 14.2%, compared with a z score of 0.0 and 2.4% incidence of osteoporosis in 543 transmen (J Bone Min Res. 2019;34[3]:447-54).

In the prospective European Network for the Investigation of Gender Incongruence (ENIGI) study, researchers examined short-term effects of hormone therapy on BMD in 144 transwomen and 162 transmen who had a normal body mass index and were mostly white. The percentage of patients who reported they were current smokers was between 25% and 30%, and fewer than 10% said they consumed more than seven units of alcohol per week. Transwomen received estradiol (an oral estradiol valerate at a dose of 4 mg/day or an estradiol patch) together with 100 mg/day of cyproterone acetate, and transmen received testosterone in the form of a gel (50 mg/day), intramuscular esters (250 mg every 2-3 weeks), or intramuscular undecanoate at a dose of 1,000 mg every 12 weeks (J Sex Med. 2016;13[6]:994-9).

After 1 year of treatment, there were significant increases in BMD in transwomen in the lumbar spine (3.67%; 95% confidence interval, 3.20%-4.13%), femoral neck (1.86%; 95% CI, 1.41%-2.31%), and total hip (0.97%; 95% CI, 0.62%-1.31%). Transmen also had increased BMD in the lumbar spine (0.86%; 95% CI, 0.38%-1.35%) and total hip (1.04%; 95% CI, 0.64%-1.44%), with a slight decrease in femoral neck BMD (–0.46%; 95% CI, –1.07% to 0.16%).

Dr. den Heijer also discussed the long-term effects of hormone therapy on BMD in the Amsterdam Cohort of Dysphoria (ACOG) study, which consisted of 711 transwomen and 543 transmen and followed some patients out to 2 years, 5 years, and 10 years after beginning hormone therapy (J Sex Med. 2018;15[4]:582-90). Among transwomen, the median age was 33 years, 68.9% had begun hormone therapy, and 75.3% received a gonadectomy; among transmen, the median age was 25 years, 72.9% had begun hormone therapy, and 83.8% received a gonadectomy. Of these patients, dual-energy x-ray absorptiometry data were available for the lumbar spine BMD for 234 transwomen and 236 transmen at 2 years, 174 transwomen and 95 transmen at 5 years, and 102 transwomen and 70 transmen at 10 years.

Although there was no significant mean change in absolute BMD over the 10-year period, the concentration of estradiol in transwomen and transmen affected change in BMD the longer the transperson was receiving hormone therapy: Transwomen who received an estradiol concentration of 118 pmol/L had a decrease of –0.026% at 2 years, –0.044% at 5 years, and –0.009% at 10 years, compared with a dose of 443 pmol/L (+0.044% at 2 years, +0.025% at 5 years, +0.063% at 10 years), whereas transmen also had decreased BMD at the lowest estradiol concentrations of 95 pmol/L (–0.007% at 2 years, –0.024% at 5 years, +0.010% at 10 years), compared with transmen receiving the highest doses of 323 pmol/L (+0.028% at 2 years, +0.002% at 5 years, +0.053% at 10 years). There was no significant change in BMD in either group at any time point with regard to testosterone concentration.

When the investigators linked these patients to a national statistics database in the Netherlands to evaluate fracture incidence (J Bone Miner Res. 2019 Sep 5. doi: 10.1002/jbmr.3862), pairing five cisgender female controls and five cisgender male controls to every transgender patient, the researchers found transwomen had a higher incidence of osteoporotic fracture of the hip, spine, forearm, and humerus (41.8%), compared with cisgender men (26.6%; P = .014) and cisgender women (36.0%; P = .381). There was not enough information in the study to examine fracture information for transmen, Dr. den Heijer said. Transwomen and transmen who experienced a fracture were more likely to be a current smoker and have lower estradiol concentrations than were transwomen and transmen, respectively, who did not have a fracture.

“Attention for lifestyle factors remains important, especially smoking cessation, vitamin D intake, and regular exercise,” Dr. den Heijer said. “It remains important for everybody, but especially for transgender women.”

Dr. den Heijer reported no relevant conflicts of interest.
 

ORLANDO – Transwomen are more likely to have a lower bone mineral density (BMD) before beginning hormone therapy, compared with male reference populations, but there are no short- or long-term risks to bone health over the life of a transperson who receives hormone therapy, according to a presentation at the annual meeting of the American Society for Bone and Mineral Research.

“Hormonal treatment of transgender people is safe with respect to bone,” said Martin den Heijer, MD, PhD, of the VU University Medical Center in Amsterdam.

At baseline, transwomen have lower bone mass than do male reference populations, said Dr. den Heijer, citing a study that found 25 transwomen had less muscle mass (P less than or equal to .001), strength (P less than or equal to .05), and lower BMD at the hip, femoral neck, and spine (P less than .001), compared with 25 cisgender men in a control group and 941 men in a male reference population (Bone. 2013;54[1]:92-7). In a 2019 study from his own group, Dr. den Heijer said the z score in the lumbar spine for 711 transwomen was -0.9 and the incidence of osteoporosis was 14.2%, compared with a z score of 0.0 and 2.4% incidence of osteoporosis in 543 transmen (J Bone Min Res. 2019;34[3]:447-54).

In the prospective European Network for the Investigation of Gender Incongruence (ENIGI) study, researchers examined short-term effects of hormone therapy on BMD in 144 transwomen and 162 transmen who had a normal body mass index and were mostly white. The percentage of patients who reported they were current smokers was between 25% and 30%, and fewer than 10% said they consumed more than seven units of alcohol per week. Transwomen received estradiol (an oral estradiol valerate at a dose of 4 mg/day or an estradiol patch) together with 100 mg/day of cyproterone acetate, and transmen received testosterone in the form of a gel (50 mg/day), intramuscular esters (250 mg every 2-3 weeks), or intramuscular undecanoate at a dose of 1,000 mg every 12 weeks (J Sex Med. 2016;13[6]:994-9).

After 1 year of treatment, there were significant increases in BMD in transwomen in the lumbar spine (3.67%; 95% confidence interval, 3.20%-4.13%), femoral neck (1.86%; 95% CI, 1.41%-2.31%), and total hip (0.97%; 95% CI, 0.62%-1.31%). Transmen also had increased BMD in the lumbar spine (0.86%; 95% CI, 0.38%-1.35%) and total hip (1.04%; 95% CI, 0.64%-1.44%), with a slight decrease in femoral neck BMD (–0.46%; 95% CI, –1.07% to 0.16%).

Dr. den Heijer also discussed the long-term effects of hormone therapy on BMD in the Amsterdam Cohort of Dysphoria (ACOG) study, which consisted of 711 transwomen and 543 transmen and followed some patients out to 2 years, 5 years, and 10 years after beginning hormone therapy (J Sex Med. 2018;15[4]:582-90). Among transwomen, the median age was 33 years, 68.9% had begun hormone therapy, and 75.3% received a gonadectomy; among transmen, the median age was 25 years, 72.9% had begun hormone therapy, and 83.8% received a gonadectomy. Of these patients, dual-energy x-ray absorptiometry data were available for the lumbar spine BMD for 234 transwomen and 236 transmen at 2 years, 174 transwomen and 95 transmen at 5 years, and 102 transwomen and 70 transmen at 10 years.

Although there was no significant mean change in absolute BMD over the 10-year period, the concentration of estradiol in transwomen and transmen affected change in BMD the longer the transperson was receiving hormone therapy: Transwomen who received an estradiol concentration of 118 pmol/L had a decrease of –0.026% at 2 years, –0.044% at 5 years, and –0.009% at 10 years, compared with a dose of 443 pmol/L (+0.044% at 2 years, +0.025% at 5 years, +0.063% at 10 years), whereas transmen also had decreased BMD at the lowest estradiol concentrations of 95 pmol/L (–0.007% at 2 years, –0.024% at 5 years, +0.010% at 10 years), compared with transmen receiving the highest doses of 323 pmol/L (+0.028% at 2 years, +0.002% at 5 years, +0.053% at 10 years). There was no significant change in BMD in either group at any time point with regard to testosterone concentration.

When the investigators linked these patients to a national statistics database in the Netherlands to evaluate fracture incidence (J Bone Miner Res. 2019 Sep 5. doi: 10.1002/jbmr.3862), pairing five cisgender female controls and five cisgender male controls to every transgender patient, the researchers found transwomen had a higher incidence of osteoporotic fracture of the hip, spine, forearm, and humerus (41.8%), compared with cisgender men (26.6%; P = .014) and cisgender women (36.0%; P = .381). There was not enough information in the study to examine fracture information for transmen, Dr. den Heijer said. Transwomen and transmen who experienced a fracture were more likely to be a current smoker and have lower estradiol concentrations than were transwomen and transmen, respectively, who did not have a fracture.

“Attention for lifestyle factors remains important, especially smoking cessation, vitamin D intake, and regular exercise,” Dr. den Heijer said. “It remains important for everybody, but especially for transgender women.”

Dr. den Heijer reported no relevant conflicts of interest.
 

PHILADELPHIA – Women with polycystic ovary syndrome (PCOS) are at a higher risk for metabolic and psychiatric comorbidities prior to pregnancy, cardiometabolic complications during pregnancy, and cardiometabolic and psychiatric complications in the postpartum period, according to results from a prize paper at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

“Our findings do support the ACOG [American College of Obstetricians and Gynecologists] recommendations that women with PCOS should be considered a high-risk group, and during the postpartum period should be screened for cardiovascular as well as psychiatric comorbidities,” Anuja Dokras, MD, PhD, director of the Penn Polycystic Ovary Syndrome Center at the University of Pennsylvania, Philadelphia, said in her presentation.

Dr. Dokras and colleagues performed a retrospective cohort study during 2000-2016 of patients aged 18-50 years, in the Optum claims database, which comprised 42,391 women with PCOS and 795,480 women without PCOS in 50 U.S. states. Women were included in the analysis if there were data available for at least 6 months to 1 year before pregnancy and between 6 weeks and 1 year after pregnancy. The researchers looked at risk factors prior to pregnancy, such as depression, hypertension, hyperlipidemia, diabetes, obesity, smoking, and use of assisted reproductive technology. During pregnancy, Dr. Dokras and colleagues analyzed complications such as preterm birth, multiple gestation, cesarean section, gestational hypertension and diabetes, preeclampsia and eclampsia, and depression in addition to outcomes in the postpartum period, such as hypertensive complications, thrombotic disease, peripartum cardiomyopathy, heart failure, arterial complications, perinatal and postpartum depression.

“Realizing that PCOS is underreported in administrative data sets, we looked at not only the diagnosis of PCOS but also tried to combine any menstrual irregularity and hirsutism occurring simultaneously, and then doing a sensitivity analysis and looking at the population,” said Dr. Dokras. “Similarly, knowing that misclassification can be an issue in these datasets, we did the same thing amongst the controls, looking for a single diagnosis of irregular menses and hirsutism.”

Prior to pregnancy, women with PCOS in the dataset tended to have a higher rate of obesity (14.7% vs. 4.7%), hyperlipidemia (11.3% vs. 5.3%), hypertension (6.2% vs. 2.5%), diabetes (5.3% vs. 1.2%), and depression (4.3% vs. 3.1%) and were also more likely to use assisted reproductive technology (5.2% vs. 1.0%) than were patients without PCOS (all P less than .001). During pregnancy, there was a higher rate of gestational diabetes (13.7% vs. 7.7%), preeclampsia (5.0% vs. 2.6%), preterm birth (16.9% vs. 12.2%), multiple gestation (6.6% vs. 2.5%), and cesarean section (45.1% vs. 32.9%) in patients with PCOS, compared with those without PCOS (all P less than .001).

For patients in the postpartum period, women with PCOS were more likely to experience postpartum thrombotic disease (adjusted odds ratio, 1.60; 95% confidence interval, 1.23-2.09; P = .001), hypertensive heart disease (aOR, 1.45; 95% CI, 1.04-2.01; P = .027), eclampsia (aOR, 1.45; 95% CI, 1.14-1.86; P = .003), heart failure (aOR, 1.33; 95% CI, 1.08-1.64; P = .007), preeclampsia (aOR, 1.30; 95% CI, 1.17-1.45; P = than .001), and peripartum cardiomyopathy (aOR, 1.26; 95% CI, 1.03-1.54; P = .027).

With regard to depression, women with PCOS also were at greater risk of developing perinatal (aOR, 1.27; 95% CI, 1.22-1.33) and postpartum (aOR, 1.46; 95% CI, 1.36-1.57) depression, compared with women without PCOS (both P less than .001).

Dr. Dokras acknowledged the limitations of administrative datasets and noted that prospective studies need to be conducted to verify their findings.

This study was funded by a grant from the National Institutes of Health. Dr. Dokras reported being a consultant for Medtronic, AbbVie, and Ferring.

SOURCE: Dokras A, et al. ASRM 2019. Abstract O-93.

PHILADELPHIA – Women with polycystic ovary syndrome (PCOS) are at a higher risk for metabolic and psychiatric comorbidities prior to pregnancy, cardiometabolic complications during pregnancy, and cardiometabolic and psychiatric complications in the postpartum period, according to results from a prize paper at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

“Our findings do support the ACOG [American College of Obstetricians and Gynecologists] recommendations that women with PCOS should be considered a high-risk group, and during the postpartum period should be screened for cardiovascular as well as psychiatric comorbidities,” Anuja Dokras, MD, PhD, director of the Penn Polycystic Ovary Syndrome Center at the University of Pennsylvania, Philadelphia, said in her presentation.

Dr. Dokras and colleagues performed a retrospective cohort study during 2000-2016 of patients aged 18-50 years, in the Optum claims database, which comprised 42,391 women with PCOS and 795,480 women without PCOS in 50 U.S. states. Women were included in the analysis if there were data available for at least 6 months to 1 year before pregnancy and between 6 weeks and 1 year after pregnancy. The researchers looked at risk factors prior to pregnancy, such as depression, hypertension, hyperlipidemia, diabetes, obesity, smoking, and use of assisted reproductive technology. During pregnancy, Dr. Dokras and colleagues analyzed complications such as preterm birth, multiple gestation, cesarean section, gestational hypertension and diabetes, preeclampsia and eclampsia, and depression in addition to outcomes in the postpartum period, such as hypertensive complications, thrombotic disease, peripartum cardiomyopathy, heart failure, arterial complications, perinatal and postpartum depression.

“Realizing that PCOS is underreported in administrative data sets, we looked at not only the diagnosis of PCOS but also tried to combine any menstrual irregularity and hirsutism occurring simultaneously, and then doing a sensitivity analysis and looking at the population,” said Dr. Dokras. “Similarly, knowing that misclassification can be an issue in these datasets, we did the same thing amongst the controls, looking for a single diagnosis of irregular menses and hirsutism.”

Prior to pregnancy, women with PCOS in the dataset tended to have a higher rate of obesity (14.7% vs. 4.7%), hyperlipidemia (11.3% vs. 5.3%), hypertension (6.2% vs. 2.5%), diabetes (5.3% vs. 1.2%), and depression (4.3% vs. 3.1%) and were also more likely to use assisted reproductive technology (5.2% vs. 1.0%) than were patients without PCOS (all P less than .001). During pregnancy, there was a higher rate of gestational diabetes (13.7% vs. 7.7%), preeclampsia (5.0% vs. 2.6%), preterm birth (16.9% vs. 12.2%), multiple gestation (6.6% vs. 2.5%), and cesarean section (45.1% vs. 32.9%) in patients with PCOS, compared with those without PCOS (all P less than .001).

For patients in the postpartum period, women with PCOS were more likely to experience postpartum thrombotic disease (adjusted odds ratio, 1.60; 95% confidence interval, 1.23-2.09; P = .001), hypertensive heart disease (aOR, 1.45; 95% CI, 1.04-2.01; P = .027), eclampsia (aOR, 1.45; 95% CI, 1.14-1.86; P = .003), heart failure (aOR, 1.33; 95% CI, 1.08-1.64; P = .007), preeclampsia (aOR, 1.30; 95% CI, 1.17-1.45; P = than .001), and peripartum cardiomyopathy (aOR, 1.26; 95% CI, 1.03-1.54; P = .027).

With regard to depression, women with PCOS also were at greater risk of developing perinatal (aOR, 1.27; 95% CI, 1.22-1.33) and postpartum (aOR, 1.46; 95% CI, 1.36-1.57) depression, compared with women without PCOS (both P less than .001).

Dr. Dokras acknowledged the limitations of administrative datasets and noted that prospective studies need to be conducted to verify their findings.

This study was funded by a grant from the National Institutes of Health. Dr. Dokras reported being a consultant for Medtronic, AbbVie, and Ferring.

SOURCE: Dokras A, et al. ASRM 2019. Abstract O-93.

PHILADELPHIA – Women with polycystic ovary syndrome (PCOS) are at a higher risk for metabolic and psychiatric comorbidities prior to pregnancy, cardiometabolic complications during pregnancy, and cardiometabolic and psychiatric complications in the postpartum period, according to results from a prize paper at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

“Our findings do support the ACOG [American College of Obstetricians and Gynecologists] recommendations that women with PCOS should be considered a high-risk group, and during the postpartum period should be screened for cardiovascular as well as psychiatric comorbidities,” Anuja Dokras, MD, PhD, director of the Penn Polycystic Ovary Syndrome Center at the University of Pennsylvania, Philadelphia, said in her presentation.

Dr. Dokras and colleagues performed a retrospective cohort study during 2000-2016 of patients aged 18-50 years, in the Optum claims database, which comprised 42,391 women with PCOS and 795,480 women without PCOS in 50 U.S. states. Women were included in the analysis if there were data available for at least 6 months to 1 year before pregnancy and between 6 weeks and 1 year after pregnancy. The researchers looked at risk factors prior to pregnancy, such as depression, hypertension, hyperlipidemia, diabetes, obesity, smoking, and use of assisted reproductive technology. During pregnancy, Dr. Dokras and colleagues analyzed complications such as preterm birth, multiple gestation, cesarean section, gestational hypertension and diabetes, preeclampsia and eclampsia, and depression in addition to outcomes in the postpartum period, such as hypertensive complications, thrombotic disease, peripartum cardiomyopathy, heart failure, arterial complications, perinatal and postpartum depression.

“Realizing that PCOS is underreported in administrative data sets, we looked at not only the diagnosis of PCOS but also tried to combine any menstrual irregularity and hirsutism occurring simultaneously, and then doing a sensitivity analysis and looking at the population,” said Dr. Dokras. “Similarly, knowing that misclassification can be an issue in these datasets, we did the same thing amongst the controls, looking for a single diagnosis of irregular menses and hirsutism.”

Prior to pregnancy, women with PCOS in the dataset tended to have a higher rate of obesity (14.7% vs. 4.7%), hyperlipidemia (11.3% vs. 5.3%), hypertension (6.2% vs. 2.5%), diabetes (5.3% vs. 1.2%), and depression (4.3% vs. 3.1%) and were also more likely to use assisted reproductive technology (5.2% vs. 1.0%) than were patients without PCOS (all P less than .001). During pregnancy, there was a higher rate of gestational diabetes (13.7% vs. 7.7%), preeclampsia (5.0% vs. 2.6%), preterm birth (16.9% vs. 12.2%), multiple gestation (6.6% vs. 2.5%), and cesarean section (45.1% vs. 32.9%) in patients with PCOS, compared with those without PCOS (all P less than .001).

For patients in the postpartum period, women with PCOS were more likely to experience postpartum thrombotic disease (adjusted odds ratio, 1.60; 95% confidence interval, 1.23-2.09; P = .001), hypertensive heart disease (aOR, 1.45; 95% CI, 1.04-2.01; P = .027), eclampsia (aOR, 1.45; 95% CI, 1.14-1.86; P = .003), heart failure (aOR, 1.33; 95% CI, 1.08-1.64; P = .007), preeclampsia (aOR, 1.30; 95% CI, 1.17-1.45; P = than .001), and peripartum cardiomyopathy (aOR, 1.26; 95% CI, 1.03-1.54; P = .027).

With regard to depression, women with PCOS also were at greater risk of developing perinatal (aOR, 1.27; 95% CI, 1.22-1.33) and postpartum (aOR, 1.46; 95% CI, 1.36-1.57) depression, compared with women without PCOS (both P less than .001).

Dr. Dokras acknowledged the limitations of administrative datasets and noted that prospective studies need to be conducted to verify their findings.

This study was funded by a grant from the National Institutes of Health. Dr. Dokras reported being a consultant for Medtronic, AbbVie, and Ferring.

SOURCE: Dokras A, et al. ASRM 2019. Abstract O-93.

PHILADELPHIA – Factors such as primary fibroid volume, fibroid stage, and uterine volume did not appear to affect the efficacy of elagolix in improving heavy menstrual bleeding associated with uterine fibroids, according to results presented at the annual meeting of the American Society for Reproductive Medicine.

Ayman Al-Hendy, MD, PhD, director of translational research at the University of Illinois at Chicago, and associates, analyzed a pooled subgroup of 790 patients from the Elaris UF-1 and UF-2 trials who received elagolix twice daily at a dose of 300 mg (199 patients), elagolix 300 mg twice daily with add-back therapy (1 mg of estradiol plus 0.5 mg of norethindrone acetate; 395 patients), and a placebo group (196 patients) for treatment of heavy menstrual bleeding. Patients were premenopausal women aged 18-51 years with more than 80 mL of menstrual blood loss per cycle. The study design included a washout period, followed by a 2.5-month to 3.5-month screening period, and patients were randomized to 6 months of treatment with placebo, elagolix alone, or elagolix with add-back therapy in a 1:1:2 ratio. Researchers evaluated whether patients had less than 80 mL of menstrual blood loss per cycle and a 50% or more reduction in menstrual blood loss per cycle by the end of the study.

In a subgroup analysis, they also analyzed primary fibroid volume, fibroid stage, and uterine volume. The median primary fibroid volume was 36.2 cm³ (range, 1.0-1,081.5 cm³). Fibroid location was classified using the International Federation of Gynecology and Obstetrics (FIGO) staging system, and researchers placed fibroids into FIGO 0-3, FIGO 4, and FIGO 5-8 groups. At baseline, characteristics between groups were similar, but the patients who received elagolix alone had a lower number of fibroids classified as FIGO 0-3 and had a greater percentage of fibroids less than 36.2 cm³. The median uterine volume was 356.5 cm³ (range, 71.6-3,347.9 cm³).

At final follow-up, 81% of patients receiving elagolix alone and 72% of patients receiving elagolix with add-back therapy responded to treatment, compared with placebo (9%).

Patients receiving elagolix plus add-back therapy responded to treatment better than placebo, and there were no significant differences in outcomes in terms of FIGO stage: Response was as follows for patients with FIGO 0-3 classified fibroids (78% of 47 patients vs. 9% of 25 patients), FIGO 4 fibroids (68% of 177 patients vs. 15% of 85 patients) and FIGO 5-8 fibroids (74% of 165 patients vs. 4% of 82 patients). The same was true in terms of both primary fibroid volume and uterine volume in patients who received elagolix plus add-back therapy, compared with those who received placebo: Patients with a primary fibroid volume of less than 36.2 cm³ (74% of 189 patients vs. 15% of 92 patients) responded similarly to elagolix plus add-back therapy as did patients with a primary fibroid volume greater than 36.2 cm³ (70% of 200 patients vs. 5% of 100 patients), and there were no significant differences between the treatment response of patients with a uterine volume less than 365.5 cm³ (75% of 203 patients vs. 15% of 88 patients) and a uterine volume greater than 365.5 cm³ (70% of 192 patients vs. 5% of 108 patients).

“These really are very encouraging results and suggests that, in women with different fibroids, elagolix with add-back therapy would be an effective treatment option despite uterine and fibroid volume and location of fibroids,” said Dr. Al-Hendy.

Dr. Al-Hendy noted there are ongoing studies analyzing elagolix with add-back in women with fibroids, in women with endometriosis, and elagolix in women with polycystic ovary syndrome.

AbbVie recently submitted a new drug application to the Food and Drug Administration for elagolix based on results from these two trials. Elagolix, an oral GnRh receptor antagonist, is an FDA-approved oral medication for the management of endometriosis with associated moderate to severe pain.

This study was funded by AbbVie, and the company was involved in the study design, research, data collection, analysis and interpretation of the data, as well as the writing, reviewing and approving of the study for publication. The authors reported various relationships with industry, pharmaceutical companies, government entities, and other organizations.
 

SOURCE: Al-Hendy A et al. ASRM 2019, Abstract O-205.

PHILADELPHIA – Factors such as primary fibroid volume, fibroid stage, and uterine volume did not appear to affect the efficacy of elagolix in improving heavy menstrual bleeding associated with uterine fibroids, according to results presented at the annual meeting of the American Society for Reproductive Medicine.

Ayman Al-Hendy, MD, PhD, director of translational research at the University of Illinois at Chicago, and associates, analyzed a pooled subgroup of 790 patients from the Elaris UF-1 and UF-2 trials who received elagolix twice daily at a dose of 300 mg (199 patients), elagolix 300 mg twice daily with add-back therapy (1 mg of estradiol plus 0.5 mg of norethindrone acetate; 395 patients), and a placebo group (196 patients) for treatment of heavy menstrual bleeding. Patients were premenopausal women aged 18-51 years with more than 80 mL of menstrual blood loss per cycle. The study design included a washout period, followed by a 2.5-month to 3.5-month screening period, and patients were randomized to 6 months of treatment with placebo, elagolix alone, or elagolix with add-back therapy in a 1:1:2 ratio. Researchers evaluated whether patients had less than 80 mL of menstrual blood loss per cycle and a 50% or more reduction in menstrual blood loss per cycle by the end of the study.

In a subgroup analysis, they also analyzed primary fibroid volume, fibroid stage, and uterine volume. The median primary fibroid volume was 36.2 cm³ (range, 1.0-1,081.5 cm³). Fibroid location was classified using the International Federation of Gynecology and Obstetrics (FIGO) staging system, and researchers placed fibroids into FIGO 0-3, FIGO 4, and FIGO 5-8 groups. At baseline, characteristics between groups were similar, but the patients who received elagolix alone had a lower number of fibroids classified as FIGO 0-3 and had a greater percentage of fibroids less than 36.2 cm³. The median uterine volume was 356.5 cm³ (range, 71.6-3,347.9 cm³).

At final follow-up, 81% of patients receiving elagolix alone and 72% of patients receiving elagolix with add-back therapy responded to treatment, compared with placebo (9%).

Patients receiving elagolix plus add-back therapy responded to treatment better than placebo, and there were no significant differences in outcomes in terms of FIGO stage: Response was as follows for patients with FIGO 0-3 classified fibroids (78% of 47 patients vs. 9% of 25 patients), FIGO 4 fibroids (68% of 177 patients vs. 15% of 85 patients) and FIGO 5-8 fibroids (74% of 165 patients vs. 4% of 82 patients). The same was true in terms of both primary fibroid volume and uterine volume in patients who received elagolix plus add-back therapy, compared with those who received placebo: Patients with a primary fibroid volume of less than 36.2 cm³ (74% of 189 patients vs. 15% of 92 patients) responded similarly to elagolix plus add-back therapy as did patients with a primary fibroid volume greater than 36.2 cm³ (70% of 200 patients vs. 5% of 100 patients), and there were no significant differences between the treatment response of patients with a uterine volume less than 365.5 cm³ (75% of 203 patients vs. 15% of 88 patients) and a uterine volume greater than 365.5 cm³ (70% of 192 patients vs. 5% of 108 patients).

“These really are very encouraging results and suggests that, in women with different fibroids, elagolix with add-back therapy would be an effective treatment option despite uterine and fibroid volume and location of fibroids,” said Dr. Al-Hendy.

Dr. Al-Hendy noted there are ongoing studies analyzing elagolix with add-back in women with fibroids, in women with endometriosis, and elagolix in women with polycystic ovary syndrome.

AbbVie recently submitted a new drug application to the Food and Drug Administration for elagolix based on results from these two trials. Elagolix, an oral GnRh receptor antagonist, is an FDA-approved oral medication for the management of endometriosis with associated moderate to severe pain.

This study was funded by AbbVie, and the company was involved in the study design, research, data collection, analysis and interpretation of the data, as well as the writing, reviewing and approving of the study for publication. The authors reported various relationships with industry, pharmaceutical companies, government entities, and other organizations.
 

SOURCE: Al-Hendy A et al. ASRM 2019, Abstract O-205.

PHILADELPHIA – Factors such as primary fibroid volume, fibroid stage, and uterine volume did not appear to affect the efficacy of elagolix in improving heavy menstrual bleeding associated with uterine fibroids, according to results presented at the annual meeting of the American Society for Reproductive Medicine.

Ayman Al-Hendy, MD, PhD, director of translational research at the University of Illinois at Chicago, and associates, analyzed a pooled subgroup of 790 patients from the Elaris UF-1 and UF-2 trials who received elagolix twice daily at a dose of 300 mg (199 patients), elagolix 300 mg twice daily with add-back therapy (1 mg of estradiol plus 0.5 mg of norethindrone acetate; 395 patients), and a placebo group (196 patients) for treatment of heavy menstrual bleeding. Patients were premenopausal women aged 18-51 years with more than 80 mL of menstrual blood loss per cycle. The study design included a washout period, followed by a 2.5-month to 3.5-month screening period, and patients were randomized to 6 months of treatment with placebo, elagolix alone, or elagolix with add-back therapy in a 1:1:2 ratio. Researchers evaluated whether patients had less than 80 mL of menstrual blood loss per cycle and a 50% or more reduction in menstrual blood loss per cycle by the end of the study.

In a subgroup analysis, they also analyzed primary fibroid volume, fibroid stage, and uterine volume. The median primary fibroid volume was 36.2 cm³ (range, 1.0-1,081.5 cm³). Fibroid location was classified using the International Federation of Gynecology and Obstetrics (FIGO) staging system, and researchers placed fibroids into FIGO 0-3, FIGO 4, and FIGO 5-8 groups. At baseline, characteristics between groups were similar, but the patients who received elagolix alone had a lower number of fibroids classified as FIGO 0-3 and had a greater percentage of fibroids less than 36.2 cm³. The median uterine volume was 356.5 cm³ (range, 71.6-3,347.9 cm³).

At final follow-up, 81% of patients receiving elagolix alone and 72% of patients receiving elagolix with add-back therapy responded to treatment, compared with placebo (9%).

Patients receiving elagolix plus add-back therapy responded to treatment better than placebo, and there were no significant differences in outcomes in terms of FIGO stage: Response was as follows for patients with FIGO 0-3 classified fibroids (78% of 47 patients vs. 9% of 25 patients), FIGO 4 fibroids (68% of 177 patients vs. 15% of 85 patients) and FIGO 5-8 fibroids (74% of 165 patients vs. 4% of 82 patients). The same was true in terms of both primary fibroid volume and uterine volume in patients who received elagolix plus add-back therapy, compared with those who received placebo: Patients with a primary fibroid volume of less than 36.2 cm³ (74% of 189 patients vs. 15% of 92 patients) responded similarly to elagolix plus add-back therapy as did patients with a primary fibroid volume greater than 36.2 cm³ (70% of 200 patients vs. 5% of 100 patients), and there were no significant differences between the treatment response of patients with a uterine volume less than 365.5 cm³ (75% of 203 patients vs. 15% of 88 patients) and a uterine volume greater than 365.5 cm³ (70% of 192 patients vs. 5% of 108 patients).

“These really are very encouraging results and suggests that, in women with different fibroids, elagolix with add-back therapy would be an effective treatment option despite uterine and fibroid volume and location of fibroids,” said Dr. Al-Hendy.

Dr. Al-Hendy noted there are ongoing studies analyzing elagolix with add-back in women with fibroids, in women with endometriosis, and elagolix in women with polycystic ovary syndrome.

AbbVie recently submitted a new drug application to the Food and Drug Administration for elagolix based on results from these two trials. Elagolix, an oral GnRh receptor antagonist, is an FDA-approved oral medication for the management of endometriosis with associated moderate to severe pain.

This study was funded by AbbVie, and the company was involved in the study design, research, data collection, analysis and interpretation of the data, as well as the writing, reviewing and approving of the study for publication. The authors reported various relationships with industry, pharmaceutical companies, government entities, and other organizations.
 

SOURCE: Al-Hendy A et al. ASRM 2019, Abstract O-205.

PHILADELPHIA – Women with ovarian torsion had a lower rate of perioperative complications when treated with conservative surgery, compared with oophorectomy, according to results from a retrospective study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The effectiveness of laparoscopy and conservative surgery has increased in recent years, but over 75% of women with ovarian torsion in the study were treated with oophorectomy and 60% underwent a laparotomy, said Rachel S. Mandelbaum, MD, of the department of obstetrics & gynecology at the University of Southern California, Los Angeles.

“We believe that conservative surgery should be performed whenever possible in young women with ovarian torsion regardless of the appearance of the ovary intraoperatively,” said Dr. Mandelbaum.

The researchers performed a retrospective, observational study of 89,801 women in the Nationwide Inpatient Sample who were younger than age 50 years, were diagnosed with ovarian torsion during Jan. 2001–Sept. 2015, and were treated with conservative surgery or oophorectomy. Patients were excluded if they had malignancy, were older than 50 years of age, or their surgery information was unavailable. The majority of patients in the study were white (46%), nonobese (91%), without comorbidities, privately insured (59%), and were seen at a large (61%) urban hospital (51% teaching; 38% nonteaching).

Dr. Mandelbaum and colleagues found 78% of patients received a cystectomy, 19% had cyst drainage, 11% had detorsion alone, and 0.5% had an oophoropexy, with less than 10% of patients having a combination of cystectomy, cyst drainage, and oophoropexy. According to a multivariable analysis, patients who were treated with conservative surgery were more likely to be young, have a high income, live in the northeastern United States, be treated with laparoscopy, and be seen at a large hospital or teaching hospital (P less than .001). Oophorectomy was more common in patients with a high number of comorbidities and in patients with morbid obesity (P less than .001).

Between 2001 and 2015, the rate of conservative surgery increased from 19% to 25% (P less than .001); however, the rate of conservative surgery by age was nearly 40% in pediatric patients up to 15 years old, while the rate of conservative surgery declined by almost half until 35 years, followed by a further decline until age 50 years, said Dr. Mandelbaum. Use of laparoscopy also increased from 31% in 2001 to 42% in 2015 (P less than .001).

Overall, 20,643 patients underwent conservative surgery and 69,157 patients received an oophorectomy. Patients in the conservative surgery group were more likely to undergo a conservative surgery with a laparoscopic surgical approach (51%) than a laparotomy (41%), while patients receiving an oophorectomy were more likely to have a laparotomy (67%) than a laparoscopic surgical approach (33%). In 1,663 conservative surgeries (8%), the approach was unknown.

Postoperative complications were higher in the oophorectomy group (12%) than the conservative surgery (8%) group (odds ratio, 0.57; 95% confidence interval, 0.57-0.78; P less than .001), but there was a similar rate of venous thromboembolism (0.3% vs. 0.2%; P equals .568) and sepsis (0.3% vs. 0.3%; P equals .865) in each group.

Dr. Mandelbaum attributed the high rate of oophorectomies in the study to “differential uptake of evidence” in different areas of the United States, fear of complications from leaving an infected ovary in situ, or the surgeon’s belief that the ovary is not viable because of its color intraoperatively. “We know from animal and human studies that the intraoperative appearance of the ovary does not correlate to viability, and that 90% of black or blue ovaries regain function and subsequently appear normal on both transvaginal ultrasound or on a second look grossly,” she said. Oophorectomy rates also vary by surgeon, and gynecologists are more likely to perform conservative surgery, she added.

The researchers said they were unable to obtain data on specific surgical variables such as the size of the mass, time to surgery, intraoperative appearance, laterality, fertility wishes of the patient, and surgeon type. There were also no postdischarge data, or information on the timing of complications.

Dr. Mandelbaum reported no relevant conflicts of interest.

SOURCE: Mandelbaum RS et al. ASRM 2019. Abstract O-96.

PHILADELPHIA – Women with ovarian torsion had a lower rate of perioperative complications when treated with conservative surgery, compared with oophorectomy, according to results from a retrospective study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The effectiveness of laparoscopy and conservative surgery has increased in recent years, but over 75% of women with ovarian torsion in the study were treated with oophorectomy and 60% underwent a laparotomy, said Rachel S. Mandelbaum, MD, of the department of obstetrics & gynecology at the University of Southern California, Los Angeles.

“We believe that conservative surgery should be performed whenever possible in young women with ovarian torsion regardless of the appearance of the ovary intraoperatively,” said Dr. Mandelbaum.

The researchers performed a retrospective, observational study of 89,801 women in the Nationwide Inpatient Sample who were younger than age 50 years, were diagnosed with ovarian torsion during Jan. 2001–Sept. 2015, and were treated with conservative surgery or oophorectomy. Patients were excluded if they had malignancy, were older than 50 years of age, or their surgery information was unavailable. The majority of patients in the study were white (46%), nonobese (91%), without comorbidities, privately insured (59%), and were seen at a large (61%) urban hospital (51% teaching; 38% nonteaching).

Dr. Mandelbaum and colleagues found 78% of patients received a cystectomy, 19% had cyst drainage, 11% had detorsion alone, and 0.5% had an oophoropexy, with less than 10% of patients having a combination of cystectomy, cyst drainage, and oophoropexy. According to a multivariable analysis, patients who were treated with conservative surgery were more likely to be young, have a high income, live in the northeastern United States, be treated with laparoscopy, and be seen at a large hospital or teaching hospital (P less than .001). Oophorectomy was more common in patients with a high number of comorbidities and in patients with morbid obesity (P less than .001).

Between 2001 and 2015, the rate of conservative surgery increased from 19% to 25% (P less than .001); however, the rate of conservative surgery by age was nearly 40% in pediatric patients up to 15 years old, while the rate of conservative surgery declined by almost half until 35 years, followed by a further decline until age 50 years, said Dr. Mandelbaum. Use of laparoscopy also increased from 31% in 2001 to 42% in 2015 (P less than .001).

Overall, 20,643 patients underwent conservative surgery and 69,157 patients received an oophorectomy. Patients in the conservative surgery group were more likely to undergo a conservative surgery with a laparoscopic surgical approach (51%) than a laparotomy (41%), while patients receiving an oophorectomy were more likely to have a laparotomy (67%) than a laparoscopic surgical approach (33%). In 1,663 conservative surgeries (8%), the approach was unknown.

Postoperative complications were higher in the oophorectomy group (12%) than the conservative surgery (8%) group (odds ratio, 0.57; 95% confidence interval, 0.57-0.78; P less than .001), but there was a similar rate of venous thromboembolism (0.3% vs. 0.2%; P equals .568) and sepsis (0.3% vs. 0.3%; P equals .865) in each group.

Dr. Mandelbaum attributed the high rate of oophorectomies in the study to “differential uptake of evidence” in different areas of the United States, fear of complications from leaving an infected ovary in situ, or the surgeon’s belief that the ovary is not viable because of its color intraoperatively. “We know from animal and human studies that the intraoperative appearance of the ovary does not correlate to viability, and that 90% of black or blue ovaries regain function and subsequently appear normal on both transvaginal ultrasound or on a second look grossly,” she said. Oophorectomy rates also vary by surgeon, and gynecologists are more likely to perform conservative surgery, she added.

The researchers said they were unable to obtain data on specific surgical variables such as the size of the mass, time to surgery, intraoperative appearance, laterality, fertility wishes of the patient, and surgeon type. There were also no postdischarge data, or information on the timing of complications.

Dr. Mandelbaum reported no relevant conflicts of interest.

SOURCE: Mandelbaum RS et al. ASRM 2019. Abstract O-96.

PHILADELPHIA – Women with ovarian torsion had a lower rate of perioperative complications when treated with conservative surgery, compared with oophorectomy, according to results from a retrospective study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The effectiveness of laparoscopy and conservative surgery has increased in recent years, but over 75% of women with ovarian torsion in the study were treated with oophorectomy and 60% underwent a laparotomy, said Rachel S. Mandelbaum, MD, of the department of obstetrics & gynecology at the University of Southern California, Los Angeles.

“We believe that conservative surgery should be performed whenever possible in young women with ovarian torsion regardless of the appearance of the ovary intraoperatively,” said Dr. Mandelbaum.

The researchers performed a retrospective, observational study of 89,801 women in the Nationwide Inpatient Sample who were younger than age 50 years, were diagnosed with ovarian torsion during Jan. 2001–Sept. 2015, and were treated with conservative surgery or oophorectomy. Patients were excluded if they had malignancy, were older than 50 years of age, or their surgery information was unavailable. The majority of patients in the study were white (46%), nonobese (91%), without comorbidities, privately insured (59%), and were seen at a large (61%) urban hospital (51% teaching; 38% nonteaching).

Dr. Mandelbaum and colleagues found 78% of patients received a cystectomy, 19% had cyst drainage, 11% had detorsion alone, and 0.5% had an oophoropexy, with less than 10% of patients having a combination of cystectomy, cyst drainage, and oophoropexy. According to a multivariable analysis, patients who were treated with conservative surgery were more likely to be young, have a high income, live in the northeastern United States, be treated with laparoscopy, and be seen at a large hospital or teaching hospital (P less than .001). Oophorectomy was more common in patients with a high number of comorbidities and in patients with morbid obesity (P less than .001).

Between 2001 and 2015, the rate of conservative surgery increased from 19% to 25% (P less than .001); however, the rate of conservative surgery by age was nearly 40% in pediatric patients up to 15 years old, while the rate of conservative surgery declined by almost half until 35 years, followed by a further decline until age 50 years, said Dr. Mandelbaum. Use of laparoscopy also increased from 31% in 2001 to 42% in 2015 (P less than .001).

Overall, 20,643 patients underwent conservative surgery and 69,157 patients received an oophorectomy. Patients in the conservative surgery group were more likely to undergo a conservative surgery with a laparoscopic surgical approach (51%) than a laparotomy (41%), while patients receiving an oophorectomy were more likely to have a laparotomy (67%) than a laparoscopic surgical approach (33%). In 1,663 conservative surgeries (8%), the approach was unknown.

Postoperative complications were higher in the oophorectomy group (12%) than the conservative surgery (8%) group (odds ratio, 0.57; 95% confidence interval, 0.57-0.78; P less than .001), but there was a similar rate of venous thromboembolism (0.3% vs. 0.2%; P equals .568) and sepsis (0.3% vs. 0.3%; P equals .865) in each group.

Dr. Mandelbaum attributed the high rate of oophorectomies in the study to “differential uptake of evidence” in different areas of the United States, fear of complications from leaving an infected ovary in situ, or the surgeon’s belief that the ovary is not viable because of its color intraoperatively. “We know from animal and human studies that the intraoperative appearance of the ovary does not correlate to viability, and that 90% of black or blue ovaries regain function and subsequently appear normal on both transvaginal ultrasound or on a second look grossly,” she said. Oophorectomy rates also vary by surgeon, and gynecologists are more likely to perform conservative surgery, she added.

The researchers said they were unable to obtain data on specific surgical variables such as the size of the mass, time to surgery, intraoperative appearance, laterality, fertility wishes of the patient, and surgeon type. There were also no postdischarge data, or information on the timing of complications.

Dr. Mandelbaum reported no relevant conflicts of interest.

SOURCE: Mandelbaum RS et al. ASRM 2019. Abstract O-96.

ORLANDO – Clinicians shouldn't let the lack of research on osteoporosis treatment compliance and barriers to care keep them from acting on what's already known about drug therapies' effectiveness in preventing fractures.

That's the advice from leaders at the American Society for Bone and Mineral Research, who discussed recent recommendations issued from a National Institutes of Health Pathways to Prevention Workshop on the “Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention.”

Speakers at a special session of the annual meeting were in agreement on the need for more research into current barriers of osteoporosis care and new methods for increasing patient and physician compliance with recommendations.

But the focus should also be on what researchers in bone health have already learned about treating osteoporosis, “which is quite a bit,” said Benjamin Z. Leder, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, who gave the ASBMR’s perspective at the session. Dr. Leder was also first author on a perspective paper that outlined the society’s concerns about the recommendations coming from the workshop (J Bone Miner Res. 2019;34[9]:1549-51).
 

Gaps in knowledge and treatment

“We thought that [not focusing on what is already known about osteoporosis treatment] perhaps would have the potential to exacerbate the treatment gap that exists in osteoporosis therapy,” Dr. Leder said in his presentation. “We also felt that any knowledge deficits must be understood in the context of what has been unequivocally demonstrated in terms of our knowledge of osteoporosis therapies.”

That includes knowing how to identify patients at the highest risk of fracture, which medications reduce the risk of osteoporotic and osteopenic fractures, and that using these medications saves lives, Dr. Leder noted.

With limited resources in osteoporosis and the absence of any large, randomized, controlled trials or new therapies because of lack of interest from industry, stakeholders should be examining what can be done outside of trials. In osteoporosis, as is the case with any other therapeutic area or disease state, the results of randomized, placebo-controlled trials will not address every patient subgroup of interest, he said.

“Some extrapolation is always required,” Dr. Leder said. “We have to – as we treat, as we practice medicine – use the evidence we have and then try to use that to guide us when the randomized, controlled trial doesn’t answer that specific question.”

Dr. Leder also emphasized that fear of side effects such as osteonecrosis of the jaw and atypical femoral fracture are not the only barriers in osteoporosis care. Adherence is generally poor with osteoporosis treatment, and physicians usually have competing priorities when seeing their patients. “Even in the absence of the idea that these side effects are potentially paralyzing patients and physicians, we have to remember that we started from a fairly low baseline,” Dr. Leder said.

Other issues that complicate the issue of osteoporosis care are misinformation available online that may cause patients to not use medications, overestimations of the benefits of not using osteoporosis medication in favor of nondrug interventions, and conflicting, faulty, or unhelpful guidelines from medical societies, he said.

“There are a lot of issues that need to be addressed. The [Pathways to Prevention] has really done us a great service, and the ASBMR hopes to continue supporting their efforts moving forward,” he said.
 

Recommendations for secondary fracture prevention

Although there are gaps in osteoporosis treatment, there is still room to act, which the ASBMR aimed to accomplish in its Secondary Fracture Prevention Initiative, Douglas P. Kiel, MD, MPH, said in his presentation.

In 2016, the ASBMR put out a Call to Action to intensify screening for high-risk patients to prevent fractures, and 39 organizations signed on to the effort. The target population for the initiative is men and women aged 65 years or older who have experienced a vertebral or hip fracture who would ideally be appropriately evaluated, managed, and treated in a multidisciplinary clinical system with case management through systems like a fracture liaison service.

“The bottom line is, if you have a patient in this age group who has already experienced one of these fractures, they should be treated,” said Dr. Kiel, director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston and a professor of medicine at Harvard Medical School. “It doesn’t mean we should ignore other populations, but we need to start somewhere, and this was a well-defined, at-risk population.”

Consensus clinical recommendations for the initiative were recently published in the Journal of Bone and Mineral Research (J Bone Miner Res. 2019 Sep 20. doi: 10.1002/jbmr.3877), and the ASBMR plans to spread the recommendations in a wide number of areas, including through stakeholder organizations, social media, webinars, educational sessions, and in other guidelines.

The next step for the initiative is to execute the ASBMR’s Action Plan, which prioritizes challenges such as reimbursement for fracture liaison services and care coordination, establishment of a national fracture registry, and sharing the society’s messaging on osteoporosis fracture–prevention in guidelines and education services. The ASBMR is also examining whether it could take advantage of a new National Institutes of Health grant for dissemination and implementation research in health to help fund the Secondary Fracture Prevention Initiative, Dr. Kiel said.

Dr. Leder and Dr. Kiel reported no relevant financial disclosures.

ORLANDO – Clinicians shouldn't let the lack of research on osteoporosis treatment compliance and barriers to care keep them from acting on what's already known about drug therapies' effectiveness in preventing fractures.

That's the advice from leaders at the American Society for Bone and Mineral Research, who discussed recent recommendations issued from a National Institutes of Health Pathways to Prevention Workshop on the “Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention.”

Speakers at a special session of the annual meeting were in agreement on the need for more research into current barriers of osteoporosis care and new methods for increasing patient and physician compliance with recommendations.

But the focus should also be on what researchers in bone health have already learned about treating osteoporosis, “which is quite a bit,” said Benjamin Z. Leder, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, who gave the ASBMR’s perspective at the session. Dr. Leder was also first author on a perspective paper that outlined the society’s concerns about the recommendations coming from the workshop (J Bone Miner Res. 2019;34[9]:1549-51).
 

Gaps in knowledge and treatment

“We thought that [not focusing on what is already known about osteoporosis treatment] perhaps would have the potential to exacerbate the treatment gap that exists in osteoporosis therapy,” Dr. Leder said in his presentation. “We also felt that any knowledge deficits must be understood in the context of what has been unequivocally demonstrated in terms of our knowledge of osteoporosis therapies.”

That includes knowing how to identify patients at the highest risk of fracture, which medications reduce the risk of osteoporotic and osteopenic fractures, and that using these medications saves lives, Dr. Leder noted.

With limited resources in osteoporosis and the absence of any large, randomized, controlled trials or new therapies because of lack of interest from industry, stakeholders should be examining what can be done outside of trials. In osteoporosis, as is the case with any other therapeutic area or disease state, the results of randomized, placebo-controlled trials will not address every patient subgroup of interest, he said.

“Some extrapolation is always required,” Dr. Leder said. “We have to – as we treat, as we practice medicine – use the evidence we have and then try to use that to guide us when the randomized, controlled trial doesn’t answer that specific question.”

Dr. Leder also emphasized that fear of side effects such as osteonecrosis of the jaw and atypical femoral fracture are not the only barriers in osteoporosis care. Adherence is generally poor with osteoporosis treatment, and physicians usually have competing priorities when seeing their patients. “Even in the absence of the idea that these side effects are potentially paralyzing patients and physicians, we have to remember that we started from a fairly low baseline,” Dr. Leder said.

Other issues that complicate the issue of osteoporosis care are misinformation available online that may cause patients to not use medications, overestimations of the benefits of not using osteoporosis medication in favor of nondrug interventions, and conflicting, faulty, or unhelpful guidelines from medical societies, he said.

“There are a lot of issues that need to be addressed. The [Pathways to Prevention] has really done us a great service, and the ASBMR hopes to continue supporting their efforts moving forward,” he said.
 

Recommendations for secondary fracture prevention

Although there are gaps in osteoporosis treatment, there is still room to act, which the ASBMR aimed to accomplish in its Secondary Fracture Prevention Initiative, Douglas P. Kiel, MD, MPH, said in his presentation.

In 2016, the ASBMR put out a Call to Action to intensify screening for high-risk patients to prevent fractures, and 39 organizations signed on to the effort. The target population for the initiative is men and women aged 65 years or older who have experienced a vertebral or hip fracture who would ideally be appropriately evaluated, managed, and treated in a multidisciplinary clinical system with case management through systems like a fracture liaison service.

“The bottom line is, if you have a patient in this age group who has already experienced one of these fractures, they should be treated,” said Dr. Kiel, director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston and a professor of medicine at Harvard Medical School. “It doesn’t mean we should ignore other populations, but we need to start somewhere, and this was a well-defined, at-risk population.”

Consensus clinical recommendations for the initiative were recently published in the Journal of Bone and Mineral Research (J Bone Miner Res. 2019 Sep 20. doi: 10.1002/jbmr.3877), and the ASBMR plans to spread the recommendations in a wide number of areas, including through stakeholder organizations, social media, webinars, educational sessions, and in other guidelines.

The next step for the initiative is to execute the ASBMR’s Action Plan, which prioritizes challenges such as reimbursement for fracture liaison services and care coordination, establishment of a national fracture registry, and sharing the society’s messaging on osteoporosis fracture–prevention in guidelines and education services. The ASBMR is also examining whether it could take advantage of a new National Institutes of Health grant for dissemination and implementation research in health to help fund the Secondary Fracture Prevention Initiative, Dr. Kiel said.

Dr. Leder and Dr. Kiel reported no relevant financial disclosures.

ORLANDO – Clinicians shouldn't let the lack of research on osteoporosis treatment compliance and barriers to care keep them from acting on what's already known about drug therapies' effectiveness in preventing fractures.

That's the advice from leaders at the American Society for Bone and Mineral Research, who discussed recent recommendations issued from a National Institutes of Health Pathways to Prevention Workshop on the “Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention.”

Speakers at a special session of the annual meeting were in agreement on the need for more research into current barriers of osteoporosis care and new methods for increasing patient and physician compliance with recommendations.

But the focus should also be on what researchers in bone health have already learned about treating osteoporosis, “which is quite a bit,” said Benjamin Z. Leder, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, who gave the ASBMR’s perspective at the session. Dr. Leder was also first author on a perspective paper that outlined the society’s concerns about the recommendations coming from the workshop (J Bone Miner Res. 2019;34[9]:1549-51).
 

Gaps in knowledge and treatment

“We thought that [not focusing on what is already known about osteoporosis treatment] perhaps would have the potential to exacerbate the treatment gap that exists in osteoporosis therapy,” Dr. Leder said in his presentation. “We also felt that any knowledge deficits must be understood in the context of what has been unequivocally demonstrated in terms of our knowledge of osteoporosis therapies.”

That includes knowing how to identify patients at the highest risk of fracture, which medications reduce the risk of osteoporotic and osteopenic fractures, and that using these medications saves lives, Dr. Leder noted.

With limited resources in osteoporosis and the absence of any large, randomized, controlled trials or new therapies because of lack of interest from industry, stakeholders should be examining what can be done outside of trials. In osteoporosis, as is the case with any other therapeutic area or disease state, the results of randomized, placebo-controlled trials will not address every patient subgroup of interest, he said.

“Some extrapolation is always required,” Dr. Leder said. “We have to – as we treat, as we practice medicine – use the evidence we have and then try to use that to guide us when the randomized, controlled trial doesn’t answer that specific question.”

Dr. Leder also emphasized that fear of side effects such as osteonecrosis of the jaw and atypical femoral fracture are not the only barriers in osteoporosis care. Adherence is generally poor with osteoporosis treatment, and physicians usually have competing priorities when seeing their patients. “Even in the absence of the idea that these side effects are potentially paralyzing patients and physicians, we have to remember that we started from a fairly low baseline,” Dr. Leder said.

Other issues that complicate the issue of osteoporosis care are misinformation available online that may cause patients to not use medications, overestimations of the benefits of not using osteoporosis medication in favor of nondrug interventions, and conflicting, faulty, or unhelpful guidelines from medical societies, he said.

“There are a lot of issues that need to be addressed. The [Pathways to Prevention] has really done us a great service, and the ASBMR hopes to continue supporting their efforts moving forward,” he said.
 

Recommendations for secondary fracture prevention

Although there are gaps in osteoporosis treatment, there is still room to act, which the ASBMR aimed to accomplish in its Secondary Fracture Prevention Initiative, Douglas P. Kiel, MD, MPH, said in his presentation.

In 2016, the ASBMR put out a Call to Action to intensify screening for high-risk patients to prevent fractures, and 39 organizations signed on to the effort. The target population for the initiative is men and women aged 65 years or older who have experienced a vertebral or hip fracture who would ideally be appropriately evaluated, managed, and treated in a multidisciplinary clinical system with case management through systems like a fracture liaison service.

“The bottom line is, if you have a patient in this age group who has already experienced one of these fractures, they should be treated,” said Dr. Kiel, director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston and a professor of medicine at Harvard Medical School. “It doesn’t mean we should ignore other populations, but we need to start somewhere, and this was a well-defined, at-risk population.”

Consensus clinical recommendations for the initiative were recently published in the Journal of Bone and Mineral Research (J Bone Miner Res. 2019 Sep 20. doi: 10.1002/jbmr.3877), and the ASBMR plans to spread the recommendations in a wide number of areas, including through stakeholder organizations, social media, webinars, educational sessions, and in other guidelines.

The next step for the initiative is to execute the ASBMR’s Action Plan, which prioritizes challenges such as reimbursement for fracture liaison services and care coordination, establishment of a national fracture registry, and sharing the society’s messaging on osteoporosis fracture–prevention in guidelines and education services. The ASBMR is also examining whether it could take advantage of a new National Institutes of Health grant for dissemination and implementation research in health to help fund the Secondary Fracture Prevention Initiative, Dr. Kiel said.

Dr. Leder and Dr. Kiel reported no relevant financial disclosures.

PHILADELPHIA – Women taking SSRIs may experience reduced fecundity and a lower live birth rate than women who were not exposed to antidepressants, Lindsey A. Sjaarda, PhD, reported at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

In addition, women in a subgroup receiving fluoxetine experienced a lower live birth rate and greater incidence of pregnancy loss than women taking other SSRIs, but the results were not statistically significant, said Dr. Sjaarda of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

“[It] is biologically plausible that fluoxetine might have some different effects,” she noted. “It does have some different interaction with [cytochrome] P-450 enzyme activity, and this translates to it having a much longer half-life as well. It’s different in terms of drug metabolism and in its interaction with the hormone biosynthesis pathway.”

Most of the research on antidepressants and SSRIs in pregnancy has focused on the safety of the agents, rather than the effect on pregnancy for women trying to conceive, explained Dr. Sjaarda. Previous research also has shown inconsistent findings for fecundability in women of reproductive age taking SSRIs, and the risk of specific SSRI compounds on pregnancy loss is unclear.

The researchers performed a longitudinal exposure assessment of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, which consisted of 1,228 women aged between 18 and 40 years trying to conceive. Patients were included if they had one to two prior pregnancy losses, up to two live births, and had been trying to become pregnant for six menstrual cycles; they were excluded if they had a severe history of mental illness. There were 1,035 women who had no preconception antidepressant exposure and 183 who did have preconception antidepressant exposure.

Patients provided longitudinal urine samples at various time points, including while trying to conceive and in early pregnancy, during the menses phase of each menstrual cycle and at their last menstrual cycle, and at 4 and 8 weeks’ gestation if they become pregnant. The urine samples were collected at home or in clinic; human chorionic gonadotropin levels were measured on the stored samples. The researchers defined pregnancy loss as any kind of loss measured after detecting human chorionic gonadotropin, and they used the patient’s medical record to determine live birth. The fecundability odds ratio was used to estimate the odds of conception in menstrual cycles.

Wavebreakmedia Ltd/Thinkstock

Aypical and tricyclic antidepressants and SSRIs such as sertraline, fluoxetine, and citalopram/escitalopram were analyzed, as well as use of opioids, cannabinoids, and benzodiazepines. In total, 172 women used SSRIs, which represented 94% of the patient group analyzed, said Dr. Sjaarda. “This cohort really represents women who are successfully controlled with first-line agents.”

Patients in both the SSRI and no-antidepressant groups had similar baseline characteristics, but there were differences with regard to body mass index (26 kg/m² vs. 28 kg/m²), employment status (77% vs. 67%), perceived stress (1.0 vs. 0.9), and opioid exposure (16% vs. 23%).

The researchers found use of any SSRI was associated with a 23% reduction in fecundability, with patients using fluoxetine, sertraline, and citalopram/escitalopram having a similar reduction in fecundability, compared with patients not using SSRIs.

Patients who received SSRIs also had approximately a 53% live birth rate overall. When analyzed by individual SSRI, however, there was a statistically significant reduction in the live birth rate for patients who were using fluoxetine, compared with patients using sertraline and citalopram/escitalopram. “This suggests that there was something besides just reduced fecundability going on with the fluoxetine-exposed women,” said Dr. Sjaarda.

When SSRI use was analyzed with regard to pregnancy loss, there was a generally null effect between women exposed to SSRIs overall versus those not exposed at the time before conception, at last menstrual period, and at 4 or 8 weeks’ gestation. But when grouped by specific SSRI, patients receiving fluoxetine had increased risk of pregnancy loss prior to conception, compared with patients not taking fluoxetine (34% vs. 24%; adjusted risk ratio, 1.41; 95% confidence interval, 0.94-2.12) , as well as at their last menstrual period (34% vs. 24%; adjusted RR, 1.48; 95% CI, 0.98-2.24) and at 4 weeks of pregnancy (31% vs. 22%; adjusted RR, 1.61; 95% CI, 0.94-2.78). “This was about a 40%-60% increase in pregnancy loss, even though the sample size is generally small when you divide it into these groups,” said Dr. Sjaarda.

Mental health care is an important public health and maternal health issue, and SSRIs as a drug class are essential for helping to appropriately manage mental health, noted Dr. Sjaarda.

Because “patients’ disease severities all vary and the reactions to different drugs vary, no one-size-fits-all recommendation can be made for people planning a pregnancy while using SSRIs,” concluded Dr. Sjaarda. “However, we’re hoping that women and their physicians can now consider these new data, which are based on objective and longitudinally measured exposure, as well as prospectively-assessed outcomes for these most common antidepressants and develop to a more informed and individualized plan for women who are trying to conceive and use SSRIs.”

Dr. Sjaarda reported no relevant conflicts of interest.

SOURCE: Sjaarda L et al. ASRM 2019, Abstract O-1.

PHILADELPHIA – Women taking SSRIs may experience reduced fecundity and a lower live birth rate than women who were not exposed to antidepressants, Lindsey A. Sjaarda, PhD, reported at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

In addition, women in a subgroup receiving fluoxetine experienced a lower live birth rate and greater incidence of pregnancy loss than women taking other SSRIs, but the results were not statistically significant, said Dr. Sjaarda of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

“[It] is biologically plausible that fluoxetine might have some different effects,” she noted. “It does have some different interaction with [cytochrome] P-450 enzyme activity, and this translates to it having a much longer half-life as well. It’s different in terms of drug metabolism and in its interaction with the hormone biosynthesis pathway.”

Most of the research on antidepressants and SSRIs in pregnancy has focused on the safety of the agents, rather than the effect on pregnancy for women trying to conceive, explained Dr. Sjaarda. Previous research also has shown inconsistent findings for fecundability in women of reproductive age taking SSRIs, and the risk of specific SSRI compounds on pregnancy loss is unclear.

The researchers performed a longitudinal exposure assessment of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, which consisted of 1,228 women aged between 18 and 40 years trying to conceive. Patients were included if they had one to two prior pregnancy losses, up to two live births, and had been trying to become pregnant for six menstrual cycles; they were excluded if they had a severe history of mental illness. There were 1,035 women who had no preconception antidepressant exposure and 183 who did have preconception antidepressant exposure.

Patients provided longitudinal urine samples at various time points, including while trying to conceive and in early pregnancy, during the menses phase of each menstrual cycle and at their last menstrual cycle, and at 4 and 8 weeks’ gestation if they become pregnant. The urine samples were collected at home or in clinic; human chorionic gonadotropin levels were measured on the stored samples. The researchers defined pregnancy loss as any kind of loss measured after detecting human chorionic gonadotropin, and they used the patient’s medical record to determine live birth. The fecundability odds ratio was used to estimate the odds of conception in menstrual cycles.

Wavebreakmedia Ltd/Thinkstock

Aypical and tricyclic antidepressants and SSRIs such as sertraline, fluoxetine, and citalopram/escitalopram were analyzed, as well as use of opioids, cannabinoids, and benzodiazepines. In total, 172 women used SSRIs, which represented 94% of the patient group analyzed, said Dr. Sjaarda. “This cohort really represents women who are successfully controlled with first-line agents.”

Patients in both the SSRI and no-antidepressant groups had similar baseline characteristics, but there were differences with regard to body mass index (26 kg/m² vs. 28 kg/m²), employment status (77% vs. 67%), perceived stress (1.0 vs. 0.9), and opioid exposure (16% vs. 23%).

The researchers found use of any SSRI was associated with a 23% reduction in fecundability, with patients using fluoxetine, sertraline, and citalopram/escitalopram having a similar reduction in fecundability, compared with patients not using SSRIs.

Patients who received SSRIs also had approximately a 53% live birth rate overall. When analyzed by individual SSRI, however, there was a statistically significant reduction in the live birth rate for patients who were using fluoxetine, compared with patients using sertraline and citalopram/escitalopram. “This suggests that there was something besides just reduced fecundability going on with the fluoxetine-exposed women,” said Dr. Sjaarda.

When SSRI use was analyzed with regard to pregnancy loss, there was a generally null effect between women exposed to SSRIs overall versus those not exposed at the time before conception, at last menstrual period, and at 4 or 8 weeks’ gestation. But when grouped by specific SSRI, patients receiving fluoxetine had increased risk of pregnancy loss prior to conception, compared with patients not taking fluoxetine (34% vs. 24%; adjusted risk ratio, 1.41; 95% confidence interval, 0.94-2.12) , as well as at their last menstrual period (34% vs. 24%; adjusted RR, 1.48; 95% CI, 0.98-2.24) and at 4 weeks of pregnancy (31% vs. 22%; adjusted RR, 1.61; 95% CI, 0.94-2.78). “This was about a 40%-60% increase in pregnancy loss, even though the sample size is generally small when you divide it into these groups,” said Dr. Sjaarda.

Mental health care is an important public health and maternal health issue, and SSRIs as a drug class are essential for helping to appropriately manage mental health, noted Dr. Sjaarda.

Because “patients’ disease severities all vary and the reactions to different drugs vary, no one-size-fits-all recommendation can be made for people planning a pregnancy while using SSRIs,” concluded Dr. Sjaarda. “However, we’re hoping that women and their physicians can now consider these new data, which are based on objective and longitudinally measured exposure, as well as prospectively-assessed outcomes for these most common antidepressants and develop to a more informed and individualized plan for women who are trying to conceive and use SSRIs.”

Dr. Sjaarda reported no relevant conflicts of interest.

SOURCE: Sjaarda L et al. ASRM 2019, Abstract O-1.

PHILADELPHIA – Women taking SSRIs may experience reduced fecundity and a lower live birth rate than women who were not exposed to antidepressants, Lindsey A. Sjaarda, PhD, reported at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

In addition, women in a subgroup receiving fluoxetine experienced a lower live birth rate and greater incidence of pregnancy loss than women taking other SSRIs, but the results were not statistically significant, said Dr. Sjaarda of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

“[It] is biologically plausible that fluoxetine might have some different effects,” she noted. “It does have some different interaction with [cytochrome] P-450 enzyme activity, and this translates to it having a much longer half-life as well. It’s different in terms of drug metabolism and in its interaction with the hormone biosynthesis pathway.”

Most of the research on antidepressants and SSRIs in pregnancy has focused on the safety of the agents, rather than the effect on pregnancy for women trying to conceive, explained Dr. Sjaarda. Previous research also has shown inconsistent findings for fecundability in women of reproductive age taking SSRIs, and the risk of specific SSRI compounds on pregnancy loss is unclear.

The researchers performed a longitudinal exposure assessment of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, which consisted of 1,228 women aged between 18 and 40 years trying to conceive. Patients were included if they had one to two prior pregnancy losses, up to two live births, and had been trying to become pregnant for six menstrual cycles; they were excluded if they had a severe history of mental illness. There were 1,035 women who had no preconception antidepressant exposure and 183 who did have preconception antidepressant exposure.

Patients provided longitudinal urine samples at various time points, including while trying to conceive and in early pregnancy, during the menses phase of each menstrual cycle and at their last menstrual cycle, and at 4 and 8 weeks’ gestation if they become pregnant. The urine samples were collected at home or in clinic; human chorionic gonadotropin levels were measured on the stored samples. The researchers defined pregnancy loss as any kind of loss measured after detecting human chorionic gonadotropin, and they used the patient’s medical record to determine live birth. The fecundability odds ratio was used to estimate the odds of conception in menstrual cycles.

Wavebreakmedia Ltd/Thinkstock

Aypical and tricyclic antidepressants and SSRIs such as sertraline, fluoxetine, and citalopram/escitalopram were analyzed, as well as use of opioids, cannabinoids, and benzodiazepines. In total, 172 women used SSRIs, which represented 94% of the patient group analyzed, said Dr. Sjaarda. “This cohort really represents women who are successfully controlled with first-line agents.”

Patients in both the SSRI and no-antidepressant groups had similar baseline characteristics, but there were differences with regard to body mass index (26 kg/m² vs. 28 kg/m²), employment status (77% vs. 67%), perceived stress (1.0 vs. 0.9), and opioid exposure (16% vs. 23%).

The researchers found use of any SSRI was associated with a 23% reduction in fecundability, with patients using fluoxetine, sertraline, and citalopram/escitalopram having a similar reduction in fecundability, compared with patients not using SSRIs.

Patients who received SSRIs also had approximately a 53% live birth rate overall. When analyzed by individual SSRI, however, there was a statistically significant reduction in the live birth rate for patients who were using fluoxetine, compared with patients using sertraline and citalopram/escitalopram. “This suggests that there was something besides just reduced fecundability going on with the fluoxetine-exposed women,” said Dr. Sjaarda.

When SSRI use was analyzed with regard to pregnancy loss, there was a generally null effect between women exposed to SSRIs overall versus those not exposed at the time before conception, at last menstrual period, and at 4 or 8 weeks’ gestation. But when grouped by specific SSRI, patients receiving fluoxetine had increased risk of pregnancy loss prior to conception, compared with patients not taking fluoxetine (34% vs. 24%; adjusted risk ratio, 1.41; 95% confidence interval, 0.94-2.12) , as well as at their last menstrual period (34% vs. 24%; adjusted RR, 1.48; 95% CI, 0.98-2.24) and at 4 weeks of pregnancy (31% vs. 22%; adjusted RR, 1.61; 95% CI, 0.94-2.78). “This was about a 40%-60% increase in pregnancy loss, even though the sample size is generally small when you divide it into these groups,” said Dr. Sjaarda.

Mental health care is an important public health and maternal health issue, and SSRIs as a drug class are essential for helping to appropriately manage mental health, noted Dr. Sjaarda.

Because “patients’ disease severities all vary and the reactions to different drugs vary, no one-size-fits-all recommendation can be made for people planning a pregnancy while using SSRIs,” concluded Dr. Sjaarda. “However, we’re hoping that women and their physicians can now consider these new data, which are based on objective and longitudinally measured exposure, as well as prospectively-assessed outcomes for these most common antidepressants and develop to a more informed and individualized plan for women who are trying to conceive and use SSRIs.”

Dr. Sjaarda reported no relevant conflicts of interest.

SOURCE: Sjaarda L et al. ASRM 2019, Abstract O-1.