Unexpected effects of GLP-1 drugs on women's health

GLP-1 RA has emerged as a promising therapeutic agent in the management of PCOS metabolism and hormonal disorders. Originally developed for T2D, these agents increase insulin sensitivity by reducing insulin resistance, as demonstrated by a significant reduction in the homeostatic model assessment of insulin resistance (HOMA-IR) scores.

Improved insulin sensitivity is closely associated with positive changes in body composition, important for PCOS patients with frequent obesity, such as reduced BMI and reduced waist perimeter.²

Furthermore, GLP-1 RAS has been shown to regulate the hormonal environment of PCOS. They are demonstrated by a reduction in total testosterone and dehydroepiandrosterone sulfate (DHEAS), simultaneously increasing sex hormone-binding globulin (SHBG) levels, while contributing to a mild reduction in androgen levels. These shifts can help restore a more balanced hormonal profile and may alleviate hyperandrogenism, which underlies many PCOS symptoms.²

In addition to improving metabolism and androgens, GLP-1 RA appears to have a positive effect on the menstrual cycle. Improved insulin sensitivity and direct effects on the hypothalamus-pituitary-avian axis may promote more regular ovulation cycles and improve fertility outcomes.²

GLP-1RA shows benefits in restoring ovulation, particularly in women with PCOS, by improving insulin sensitivity and lowering androgen levels. However, endometrial acceptability and its impact on implantation remained unknown.^2,3

GLP-1RA affects the hypothalamus-pituitary avian axis, promotes gonadotropin secretion and improves ovarian function. This supports fertility, but there are continuing concerns about the impact on early pregnancy.

Limited data suggest that GLP-1RA may alter endometrial acceptability and may potentially affect the success rate of implantation. Animal studies show that GLP-1RA treatment improves ovarian morphology in PCOS models, but human data is sparse.^2,3

During pregnancy, GLP-1RA can affect fetal development due to its metabolic effects. Current guidelines advise that teratogenicity risk be cancelled before conception because of unknown risk of teratogenicity. Furthermore, the effect on placental function and fetal growth requires further investigation.³

Overall, GLP-1RA offers the promise of reproductive medicine, particularly for obesity-related infertility. However, safety and efficacy in pregnancy requires more research to determine optimal use in fertile treatment and assisted breeding techniques (ART).³

GLP-1RA can affect bone metabolism and reduce the risk of osteoporosis by promoting bone formation and reducing resorption. However, some studies have shown that the risk of fractures is increased, possibly due to weight loss-related reductions in bone mineral density (BMD).⁴

Postmenopausal women who are already at increased risk of osteoporosis may benefit from the anabolic effect of GLP-1RA on bone, but data on long-term fracture risk remain conclusive.

The cardiovascular benefits of GLP-1RAS have been established, with clinical trials showing reduced major adverse cardiovascular events (MACEs), improved endothelial function, and lower blood pressure. These benefits are particularly relevant in women who are often at high risk for atypical cardiovascular symptoms and heart failure.^4,5

Despite these benefits, concerns about potential adverse effects, including gastrointestinal intolerance and cardiovascular indications that may affect bone health, ensure further investigation.

When prescribing GLP-1RA to women, especially those with osteoporosis or high cardiovascular risk, a personalized approach that considers individual bone and cardiovascular risk profiles is essential.^4,5

The role of GLP-1 receptor agonists for weight lossplay