Effects of weight loss and weight regain on androgen levels and insulin resistance in PCOS.

The Effect and Mechanism Of Weight Cycling on Hyperandrogenemia And Insulin Resistance in Polycystic Ovary Syndrome

This program sees if a high-protein diet with exercise and behavioral support, and different amounts of weight loss or regain, improve androgen levels and insulin resistance in women with PCOS.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 425 (estimated)
• Ages: 18 Years to 45 Years
• Sex: All
• Sponsor: Peking Union Medical College Hospital (Academic / other)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06545721 on ClinicalTrials.gov

What this trial studies

This is a single-center, prospective cohort enrolling about 425 women with PCOS split into a normal-weight group and an overweight/obese group. Overweight/obese participants receive an intensive high-protein diet plus exercise and behavioral interventions for weight loss, while normal-weight participants receive energy-control and behavior support to prevent weight gain. Participants are followed at 3 and 6 months and categorized by percent weight change (<2%, 2–5%, 5–10%, ≥10%) to compare changes in insulin resistance, androgen levels, and inflammatory markers. The study also includes genetic/transcriptome analyses to explore molecular mechanisms linking weight change and weight cycling to PCOS manifestations.

Who should consider this trial

Good fit: Women aged 18–45 with PCOS by Rotterdam criteria who are willing to follow dietary, exercise, and behavioral programs and who fall into the study BMI ranges (normal 18.5–<24 kg/m2 or BMI ≥24 kg/m2) are ideal candidates.

Not a fit: Women who are pregnant, breastfeeding, planning pregnancy within six months, currently using prescription weight‑loss medications, with prior bariatric surgery, or with severe cardiovascular, cerebrovascular, or liver disease are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, the results could clarify how much weight loss is needed to improve hormones and insulin resistance in PCOS and help set personalized weight‑loss targets.

How similar studies have performed: Previous research shows that modest weight loss often improves metabolic and reproductive outcomes in PCOS, but the specific effects of different weight‑loss thresholds and of weight cycling, especially at the transcriptome level, are less well characterized.

Eligibility criteria

Inclusion Criteria:

1. Women aged 18-45 years in the reproductive period;
2. Women who have previously met the Rotterdam diagnostic criteria (at least 2 of the following 3 criteria have been confirmed, and have been diagnosed with PCOS): 1) Oligomenorrhea and/or anovulation; 2) clinical and/or biochemical evidence of hyperandrogenism; 3) ultrasound showing the presence of unilateral or bilateral polycystic ovaries;
3. Inclusion of 50 women in the normal weight group: 18.5 kg/m² ≤ BMI \< 24 kg/m²; Inclusion of 400 women in the overweight/obese group: BMI ≥ 24 kg/m²;
4. Voluntarily participate in the intervention and sign an informed consent form.

Exclusion Criteria:

1. Currently pregnant or lactating, or have had a recent (within 6 months) plan for pregnancy;
2. Currently using known prescription weight loss medications (such as GLP-1RA, orlistat, topiramate, etc.);
3. History of weight loss surgery;
4. History of severe cardiovascular or cerebrovascular diseases; severe liver or kidney dysfunction (ALT \> 3 times the upper limit of normal, or creatinine \> 1.5 times the upper limit of normal); chronic or active gastrointestinal inflammatory diseases; severe systemic diseases; active malignant tumors;
5. Secondary obesity: including hypothalamic or pituitary obesity, obesity secondary to glucocorticoid use, hypogonadism-induced obesity, etc.;
6. Known history of serious endocrine system diseases;
7. Poor compliance with planned dietary interventions (psychiatric disorders such as binge eating disorder, anorexia nervosa, severe anxiety/depression);
8. Unable to follow up on time or deemed non-cooperative by the investigator.

Where this trial is running

Beijing, Beijing Municipality

• Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Wei Chen, PhD — Peking Union Medical College Hospital
• Study coordinator: Wei Chen, PhD

Conditions Polycystic Ovary Syndrome; Weight Cycling; Hyperandrogenemia; Insulin Resistance; High-protein diet; Transcriptome; Metabolome; Inflammatory status