Effect of Orlistat on Metabolic and Hormonal Features in Women With Polycystic Ovary Syndrome (PCOS): a Randomized Controlled Clinical Trial

Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders affecting women of reproductive age and is frequently associated with obesity, insulin resistance, dyslipidemia, and hormonal imbalance. Lifestyle modification remains the cornerstone of management; however, additional therapeutic options are needed to improve metabolic and reproductive outcomes. Orlistat, a gastrointestinal lipase inhibitor, promotes weight reduction by decreasing dietary fat absorption and has demonstrated potential benefits in improving insulin resistance and lipid metabolism.

This study is a single-center, randomized controlled clinical trial to be conducted at Ayub Teaching Hospital, Abbottabad. A total of 120 women aged 18-45 years with PCOS diagnosed according to the Rotterdam criteria will be enrolled and randomly allocated in a 1:1 ratio to either the intervention group or the control group. Participants in the intervention group will receive orlistat capsules twice daily in addition to standard lifestyle advice, while participants in the control group will receive placebo together with the same lifestyle recommendations, including a healthy diet and regular physical activity. The intervention period will last three months.

Participants will undergo baseline assessment, telephone follow-up visits at one and two months to monitor treatment adherence, and a final in-person assessment after three months. The primary outcome is improvement in at least one abnormality defined by the Rotterdam diagnostic criteria. Secondary outcomes include changes in sex hormone profile (LH, FSH, LH/FSH ratio, AMH, and free testosterone), fasting glucose and insulin parameters, HbA1c, lipid profile, liver function tests, lipid accumulation product, hepatic steatosis index, ultrasound grading of non-alcoholic fatty liver disease, anthropometric measures, and PCOS-related quality of life. The findings of this study will provide evidence regarding the effectiveness of orlistat as an adjunct to lifestyle modification for improving the metabolic and hormonal manifestations of PCOS in women.

Inclusion criteria

• Females aged 18-45 years.
• Diagnosis of polycystic ovary syndrome (PCOS) according to the Rotterdam Criteria (presence of any two of the following):
• Oligomenorrhea or amenorrhea.
• Clinical or biochemical hyperandrogenism.
• Polycystic ovaries on ultrasonography.
• Body mass index (BMI) between 18.5 and 35 kg/m² (Asian criteria).

Exclusion criteria

• Current or recent use of oral contraceptives, ovulation induction medications, anti-obesity medications, cholesterol-lowering medications, or other therapies/supplements known to affect insulin physiology or androgen metabolism (e.g., inositols, curcumin, lipoic acid, cinnamon, gymnemic, or other botanical extracts).
• Women undergoing in vitro fertilization (IVF) treatment.
• Known congenital adrenal hyperplasia, thyroid disorders, hyperprolactinemia, or diabetes mellitus.
• Presence of severe renal or liver disease.
• Menopausal, pregnant, or breastfeeding women.
• Anti-Müllerian Hormone (AMH) < 0.7 ng/mL.