GLP1RAs treatment may improve reproductive health in obese PCOS patients

The study findings published in BMC Endocrine Disorders showed that GLP1RA prescription improves hormonal parameters, natural pregnancy rate, menstrual regularity, and insulin sensitivity in patients with PCOS. Glucagon-like peptide 1 is one of the most thoroughly studied incretins and its receptors are expressed widely in the gastrointestinal tract, pancreas, heart, and brain.

Polycystic ovary syndrome is a common disorder that affects 4 to 21% of reproductive-age women and is the leading cause of anovulatory infertility. PCOS also affects the overall health of women with long-lasting effects even in the post-menstrual period, apart from its impact on ovulatory dysfunction.

PCOS women are suggested to benefit from GLP1RA treatment, particularly the obese population. A few clinical trials have shown that the administration of GLP1RAs improves obesity, menstrual frequency, pregnancy rate, excess of insulin and androgen levels in patients with PCOS.

The main focus of the former meta-analysis was on metabolic, anthropometric, and hormonal changes after GLP1RA administration. None investigated pregnancy outcomes or conception rate changes which disturbed most patients. Lan Shou, Hangzhou Normal University, Hangzhou, China, and colleagues aimed to evaluate the role of GLP1RAs in PCOS management, especially in reproductive health by conducting a meta-analysis.

For this purpose, the researchers conducted searches of the published literature up to September 2022. Data was obtained from randomized controlled trials (RCTs) to assess the effects of GLP1RAs in PCOS women. Standardized mean difference, weighted mean difference and risk ratios were employed for effect size estimation using a random-effects model. Eight hundred and forty patients were included; 469 individuals in the GLP1RAs group and 371 individuals in the control group from 11 RCTs.

The researchers reported the following findings:

• GLP1RA usage was associated with an improvement in natural pregnancy rate (RR: 1.72) and menstrual regularity (SMD: 1.72).
• There were no statistically significant differences in total pregnancy rate or IVF pregnancy rate between the two groups, but total PR elevated in a short time after GLP1RAs as shown in subgroup analysis.
• Randomization to GLP1RAs treatment was associated with great improvement in BMI, HOMA-IR, waist circumference (WC), sex hormone binding globulin (SHBG) and a slight reduction in TT compared to the control group.
• In the European population, a reduction in total body fat (TBF) was seen.
• GLP1RAs monotherapy was not superior to metformin when it came to fT, DHEAS, and free androgen index (FAI).

Our findings reveal that GLP-1RA use contributes to a more regular menstrual frequency and a higher natural pregnancy rate, improvement in insulin resistance, obesity, and gonadal parameters, mainly on SHBG. The researchers noted that GLP1RA in obese PCOS patients can be a new treatment option beyond the goal of weight loss.

"A more large-scale, long-term, phenotype-specific, multi-ethnic, well-designed trials are warranted to confirm the safety and efficacy of GLP1RAs in pre-conceptional PCOS women," the researchers wrote. "Besides, there is a need for intensive research into the mechanisms by which GLP1RAs affect reproductive health."

Reference:

Zhou, L., Qu, H., Yang, L. et al. Effects of GLP1RAs on pregnancy rate and menstrual cyclicity in women with polycystic ovary syndrome: a meta-analysis and systematic review. BMC Endocr Disord 23, 245 (2023). https://doi.org/10.1186/s12902-023-01500-5