Weight loss remains one of the most important arms in obese patients with polycystic ovary syndrome (PCOS). Further studies are needed to identify the best treatment.
Objective
To evaluate the effects of exenatide (EXE) on reproductive and metabolic function in overweight/obese (OW/OB) PCOS.
Design
This is a 24-week open-label prospective, randomized, clinical study.
PATIENTS AND MEASUREMENTS: This study randomized 176 OW/OB women diagnosed with PCOS to receive either EXE 10 μg BID (n = 88) or metformin (MET) 1000 mg BID (n = 88) for the first 12 weeks. Then all patients were treated with MET alone during the second 12 weeks. We observed metabolic parameters at 0 and 12 weeks, and then tracked the rate of pregnancy during the second 12 weeks.
Results
After the first 12 weeks of intervention, compared with MET, subjects who received EXE had significantly decreased weight (4.29 ± 1.29 kg vs 2.28 ± 0.55 kg, P < .001) and total fat% (4.67 ± 0.09% vs 1.11 ± 0.32%, P < .001), improved the homeostasis model of assessment for insulin resistance (1.30 ± 0.58 vs 0.59 ± 0.12, P < .001) and increased the menstrual frequency ratio (0.62 ± 0.12 vs 0.37 ± 0.01, P < .001). During the second 12 weeks, the rate of natural pregnancy of EXE-treated patients was significantly higher than MET-treated patients (43.60% vs 18.70%, P < .05).
Conclusions
Short-term EXE therapy was linked to significant weight loss and central adiposity reduction, which may further explain the improvements in insulin resistance, inflammatory marker and menstrual cycle, which may contribute to increasing pregnancy rates in OW/OB women with PCOS.
PMID 28834553 28834553 DOI 10.1111/cen.13454 10.1111/cen.13454 Liu et al. 2017, Liu 2017
Cite this article
Liu, X., Zhang, Y., Zheng, S. Y., Lin, R., Xie, Y. J., Chen, H., Zheng, Y. X., Liu, E., Chen, L., Yan, J. H., Xu, W., Mai, T. T., & Gong, Y. (2017). Efficacy of exenatide on weight loss, metabolic parameters and pregnancy in overweight/obese polycystic ovary syndrome.. Clinical endocrinology, 87(6), 767-774. https://doi.org/10.1111/cen.13454
Liu X, Zhang Y, Zheng SY, Lin R, Xie YJ, Chen H, Zheng YX, Liu E, Chen L, Yan JH, Xu W, Mai TT, Gong Y. Efficacy of exenatide on weight loss, metabolic parameters and pregnancy in overweight/obese polycystic ovary syndrome.. Clinical endocrinology. 2017;87(6):767-774. doi:10.1111/cen.13454
Carmina E et al., 2026·Journal of clinical medicine
Irregular menses and chronic anovulation are key components of Polyendocrine Metabolic Ovarian Syndrome (PMOS), but available treatments generally only mask the clinical problem, which presents itself again when the drugs are stopped. Because reduction of body weight in these patients is often associated with improvement of menstrual cycles, we evaluated the effects of treatment with semaglutide, a GLP-1 agonist that has emerged as an effective treatment for obesity. A total of 96 women with PMOS and body mass index (BMI) > 25 kg/m2 completed a six-month treatment protocol with semaglutide using an individualized dose-escalation regimen. Body weight, fasting glucose, insulin levels, insulin resistance (HOMA-IR), and ovulatory function were assessed before and after treatment. After six months of treatment, mean body weight decreased significantly (-11.3 ± 5%, p < 0.01). Before treatment, 83% of PMOS patients presented with oligomenorrhea and anovulatory cycles. Following treatment, ovulatory cycles were observed in 52.5% of previously anovulatory women. The results were particularly good in overweight patients, with almost 95% of these PMOS patients achieving menstrual cycle normalization and ovulation, but also in patients with mild obesity. Results were less favorable in PMOS patients with moderate or severe obesity, but 25% of these patients achieved menstrual ovulatory cycle normalization when treated with semaglutide. This study represents an important therapeutic advancement, suggesting that women with PMOS and excessive body weight should be considered for treatment with GLP-1 receptor agonists before proceeding to therapies specifically aimed at inducing normal cycles and ovulation.
Vitamin D deficiency is common in women with polycystic ovary syndrome (PCOS), with the 67-85% of women with PCOS having serum concentrations of 25-hydroxy vitamin D (25OHD) <20 ng/ml. Vitamin D deficiency may exacerbate symptoms of PCOS, with observational studies showing lower 25OHD levels were associated with insulin resistance, ovulatory and menstrual irregularities, lower pregnancy success, hirsutism, hyperandrogenism, obesity and elevated cardiovascular disease risk factors. There is some, but limited, evidence for beneficial effects of vitamin D supplementation on menstrual dysfunction and insulin resistance in women with PCOS. Vitamin D deficiency may play a role in exacerbating PCOS, and there may be a place for vitamin D supplementation in the management of this syndrome, but current evidence is limited and additional randomized controlled trials are required to confirm the potential benefits of vitamin D supplementation in this population.
Few subjects have provoked such controversy in the field of reproductive endocrinology as polycystic ovary syndrome (PCOS). It is characterized by heterogeneous clinical and endocrine features and this has led to considerable debate about its definition. The controversy has been fuelled by uncertainty about the aetiology of the syndrome. It seems probable that there are several causes of the typical ovarian appearance although, as will be discussed later, a familial basis for the disorder appears to be the most common of these. Traditionally, since the classic description of the syndrome by Stein and Leventhal in 1935, the diagnosis has rested primarily on the typical appearance of bilateral sclerocystic ovaries in women presenting with anovulation or hirsutism (or both). But the results from subsequent publications indicated that there could be a wide variety of clinical presentations in women who had evidence of polycystic ovaries (PCO) at ovarian biopsy (Goldzieher & Axelrod, 1963; Goldzicher & Green, 1962; Jeffcoate, 1963; Smith et al.. 1965; Givens, 1977, 1984; Yen, 1980). Although most of the women had menstrual disorders or hirsutism, there were also those who had evidence of ovulatory cycles and others who were non-hirsute. McArthur, Ingersoll and Worcester (1958) made the important observation that women with bilateral PCO characteristically had elevated urinary excretion of luteinizing hormone (LH). When radioimmunoassay became widely available in the early 1970s the emphasis changed from diagnosis by histology to use of biochemical markers of the syndrome. The typical endocrine abnormalities in PCS were raised serum concentrations of LH and testosterone (and/or androstenedione) to which could be added, in later studies, evidence of hypersecretion of adrenal androgens and abnormalities of estrogen secretion, particularly estrone (Yen et al., 1970; Gambrell et al., 1973; Rebar et al., 1976; Baird et al.. 1977; Kandeel et al.. 1978; Yen, 1980). So great was the reliance on biochemical diagnosis that, in some studies, the appearance of the ovaries was considered to be of secondary importance. One problem has been that there has seldom been total agreement as to the biochemical definition of PCOS. Some groups, for example, have taken a raised serum LH to be important for the diagnosis (Lobo, 1985; Waldstreicher et al.. 1988). However, it was clear from early biochemical studies that some women with all the other clinical and biochemical features of PCOS had normal serum LH concentra-
tions (Givens et al., 1976; Rebar er al., 1976).
Metabolic and Endocrine Agents · GLP-1 Receptor Agonists
Becker AS et al., 2026·JBRA assisted reproduction·
Open Access
GLP-1 receptor agonists (GLP-1RAs) have gained attention as a potential adjunct in preconception care for women with polycystic ovary syndrome (PCOS) and infertility. This narrative literature review (June 2025) searched PubMed, SciELO, and LILACS using the descriptors "weight loss medication," "GLP-1 receptor agonists," "liraglutide," "semaglutide," "fertility," "PCOS," and "reproductive outcomes," including studies published between 2014 and 2025, yielding 47 relevant articles. Overall, GLP-1RAs show consistent metabolic benefits and emerging evidence of improved reproductive outcomes in PCOS, with clinical trials reporting increased menstrual regularity, ovulation, and pregnancy rates-particularly when combined with metformin. Liraglutide (1.2-3.0 mg/day) and exenatide (10 µg twice daily) have been associated with improved follicular development and endometrial receptivity. Mechanistically, GLP-1 receptors are expressed in reproductive tissues, and these agents may exert anti-inflammatory, antifibrotic, and androgen-lowering effects; liraglutide has also been reported to restore granulosa-oocyte communication via suppression of CXCL10. In one randomized trial, pregnancy rates were higher with liraglutide plus metformin (69.2%) than with metformin alone (35.4%; p<0.05). Ovulation rates up to 86% have been described with exenatide plus metformin, exceeding those observed with monotherapy. Despite these signals of benefit, GLP-1RAs remain contraindicated during pregnancy due to limited human data and fetal risks observed in animal studies; semaglutide and tirzepatide require an 8-10 week washout period prior to conception, and tirzepatide may reduce oral contraceptive effectiveness because of delayed gastric emptying. In summary, GLP-1RAs are a promising strategy for preconception management in women with PCOS and obesity-related infertility, especially in combination with metformin, but they should be avoided during pregnancy and lactation, and individualized counseling is essential to align therapy with reproductive goals.