Weight loss and exercise improve ovulation rates and live birth rates in overweight or obese women with polycystic ovarian syndrome (PCOS), according to a randomized open label study published online September 24 in the Journal of Clinical Endocrinology & Metabolism.
"Our study provides proof of concept that preconception lifestyle modification is possible and effective with beneficial metabolic and reproductive effects and minimal risk to participants," write Richard S. Legro, MD, from the Department of Obstetrics and Gynecology and the Department of Public Health Sciences at Penn State College of Medicine in Hershey, Pennsylvania, and colleagues. "In contrast, use of preconception oral contraception alone may worsen the metabolic profile with no benefit to ovulation, and possibly detriment to fertility."
The researchers randomly assigned 149 overweight or obese (body mass index, 27 - 42 kg/m2) women, aged 18 to 40 years, to one of three interventions for 16 weeks. Other than PCOS, the women had no major medical conditions or contraindications to drugs used in the study.
Fifty women were assigned to a lifestyle modification intervention aimed at achieving 7% weight loss through exercise, calorie restriction, meal replacements, and either sibutramine or orlistat weight loss drugs. Safety concerns about sibutramine led to a temporary halt in study enrollment until orlistat replaced sibutramine in March 2010. The physical activity began as aerobic activity for 5 days a week for 10 minutes' duration, which increased gradually to 30 to 35 minutes' duration.
Another group of 49 women took birth control pills (ethinyl estradiol 20 μg/1 mg norethindrone acetate), and the third group of 50 women both took oral birth control and underwent the lifestyle modifications.
At baseline, 29% of women in the oral contraception group had metabolic syndrome, as did 37% of women in the lifestyle modification group and 42% of women in the combination treatment group.
After 16 weeks, all the women received clomiphene citrate to induce ovulation and used timed intercourse for four cycles. Women in the combined intervention group had the highest cumulative ovulation rate (67.1%), followed closely by the lifestyle group (60.3%), compared with less than half the women in the oral contraception group (46.1%). The rate was significantly higher in the combined group compared with the oral contraception group, but the differences were not significant in the other two pairwise comparisons.
Approximately a quarter of the women in the lifestyle group (26.0%) and the combined intervention group (24.0%) had live births compared with 10.2% of women taking birth control only. However, the difference in live birth rates, which was the primary endpoint of the trial, did not reach statistical significance.
Five adverse events occurred, nearly all of which were associated with pregnancy.
The women in the lifestyle group lost an average 6.2% of their body weight (95% confidence interval [CI], −7.4% to −5.0%), and the women in the combined intervention group lost an average 6.4% of their body weight (95% CI, −7.6 to −5.2; P < .001).
No increased prevalence of metabolic syndrome appeared in either the lifestyle modification or combination groups, but women only taking oral contraception had more than twice the odds for having metabolic syndrome compared with baseline (odds ratio [OR], 2.47; 95% CI, 1.42 - 4.27). Women in the oral contraception group experienced an increase in triglycerides levels compared with the women in the lifestyle group, and they had poorer insulin sensitivity compared with women in the lifestyle and combination groups.
A data safety monitoring board halted enrollment in December 2012 because the live birth rates in the lifestyle modification and combination groups were so similar. "[A] value of information analysis supported that additional study would not lead to the ability to detect the difference we hypothesized," the authors note.
"The results of our preconception intervention are relevant for women with PCOS not seeking pregnancy given that these same treatments are commonly used for hirsutism, obesity, and menstrual disorders," the authors write. "The primary weakness is that our study was underpowered to detect a difference in live birth between the two lifestyle modification groups."
The research was funded by the Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Center for Research Resources, and National Center for Advancing Translational Sciences at the National Institutes of Health. Dr Legro reported receiving consulting fees from Euroscreen, Astra Zeneca, Clarus Therapeutics, Takeda, and Kindex and research funding from Ferring and Astra Zeneca. One coauthor has received research funding from AbbVie. Another coauthor serves on the Medical Advisory Board of NORA Therapeutics. Another coauthor received consulting fees from BAROnova, EnteroMedics, and Ethicon. Another coauthor owns Merck stock. The other authors have disclosed no relevant financial relationships.
J Clin Endocrinol Metabol. Published online September 24, 2015. Full text
Medscape Medical News © 2015 WebMD, LLC
Send comments and news tips to email@example.com.
Cite this: Exercise, Weight Loss Improve Fertility in Women With PCOS - Medscape - Oct 05, 2015.