Evidence That Semaglutide Represents an Important Tool for Treatment of Irregular Menses and Chronic Anovulation in Women with Polyendocrine Metabolic Ovarian Syndrome
Carmina E,Longo RA
Published July 2, 2026Journal of clinical medicine, 15(13)
Carmina, E., & Longo, R. A. (2026). Evidence That Semaglutide Represents an Important Tool for Treatment of Irregular Menses and Chronic Anovulation in Women with Polyendocrine Metabolic Ovarian Syndrome. Journal of clinical medicine, 15(13). https://doi.org/10.3390/jcm15135165
Carmina E, Longo RA. Evidence That Semaglutide Represents an Important Tool for Treatment of Irregular Menses and Chronic Anovulation in Women with Polyendocrine Metabolic Ovarian Syndrome. Journal of clinical medicine. 2026;15(13). doi:10.3390/jcm15135165
Carmina, Enrico, and Rosa Alba Longo. "Evidence That Semaglutide Represents an Important Tool for Treatment of Irregular Menses and Chronic Anovulation in Women with Polyendocrine Metabolic Ovarian Syndrome." Journal of clinical medicine, vol. 15, no. 13, 2026.
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Half of heavier non-ovulating women with PMOS / PCOS ovulated after semaglutide
In this before-and-after study, about half of 80 non-ovulating women ovulated after six months of semaglutide. The 96 women who finished treatment had polyendocrine metabolic ovarian syndrome (PMOS), formerly polycystic ovary syndrome (PCOS), and excess weight, and lifestyle programs had failed. Mean body weight fell by 11.3%.
Key Findings
Ninety-six women with PMOS / PCOS and excess body weight completed six months of semaglutide, and mean body weight decreased by 11.3% (p < 0.01).
Before treatment, 80 of the 96 women (83%) had irregular periods with cycles in which they did not ovulate. After six months, 42 of those 80 (52.5%) had ovulatory cycles.
Ovulatory cycles after treatment were present in 30 of 32 overweight women, 20 of 32 mildly obese women, and 8 of 32 women with moderate or severe obesity.
Fasting glucose, insulin, and insulin resistance (HOMA-IR) decreased significantly (p < 0.01). Of 22 women with raised fasting glucose, 16 (73%) reached normal levels.
Of 105 women selected, nine did not complete treatment: four stopped after a rise in pancreatic amylase, and five stopped because of severe gastrointestinal effects.
Interpretation
This team in Palermo, Italy tracked 96 women with PMOS / PCOS and extra body weight for six months on semaglutide, a weekly injected medicine. Each woman had tried diet and exercise first, without lasting success. Doctors checked for ovulation with a hormone blood test. They timed it to the second half of each monthly cycle, month by month, as the dose was slowly raised. Semaglutide has no safety record in human pregnancy. So every woman used birth control for all six months of the study. The authors call this a meaningful step for women who carry both PMOS / PCOS and extra weight. They say larger trials comparing semaglutide to other treatments would help confirm these numbers.
RRM Context
Restorative reproductive medicine starts by asking why a woman's body has stopped ovulating, then treats that cause so her cycles return on their own. Extra body weight and high insulin sit behind missed ovulation for many women with PMOS / PCOS. Birth control pills can hide irregular cycles for years without touching what drives them, so a woman may not learn her cycles are not ovulating until she is ready to conceive. NaProTechnology uses daily cycle charting to track, month by month, whether ovulation returns once a weight or insulin treatment begins.
Our editorial summary of this paper, not the article's abstract.
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
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