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

Overview

This randomized controlled clinical trial aims to evaluate the effect of orlistat on the metabolic and hormonal features of women with polycystic ovary syndrome (PCOS). Eligible women diagnosed with PCOS according to the Rotterdam criteria will be randomly assigned to receive either orlistat plus standard lifestyle advice or placebo plus standard lifestyle advice for three months. The study will assess the effect of orlistat on hormonal parameters, glucose metabolism, lipid profile, liver function, anthropometric measures, non-alcoholic fatty liver disease, and quality of life to determine its effectiveness as an adjunctive treatment for women with PCOS.

Detailed description

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.

Interventions

• Drug Orlistat
  Oral Orlistat capsules administered twice daily between lunch and dinner for 3 months as an adjunct to the recommended care plan for women with polycystic ovary syndrome (PCOS). Participants will also receive standard lifestyle advice, including a healthy diet, regular physical activity, walking, and cycling.
• Drug Placebo
  Matching placebo capsules administered twice daily for 3 months in addition to standard lifestyle advice, including a healthy diet, regular physical activity, walking, and cycling, for women with polycystic ovary syndrome (PCOS).
• Behavioral Standard Lifestyle Advice
  Participants will receive standardized lifestyle advice, including maintaining a healthy diet, engaging in regular physical activity, and performing at least 30 minutes of walking or cycling daily throughout the 3-month study period.

Primary outcome measures

• Polycystic Ovary Syndrome (PCOS) Features [Time frame: Baseline and 3 months]
• Luteinizing Hormone/Follicle Stimulating Hormone (LH/FSH) Ratio [Time frame: Baseline and 3 months]
• Anti-Müllerian Hormone (AMH) [Time frame: Baseline and 3 months]
• Follicle Stimulating Hormone (FSH) [Time frame: Baseline and 3 months]
• Luteinizing Hormone (LH) [Time frame: Baseline and 3 months]
• Free Testosterone [Time frame: Baseline and 3 months]
• Fasting Blood Glucose [Time frame: Baseline and 3 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Pakistan · 1 center

• Ayub Teaching Hospital — Abbottābād

Publications

• March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010 Feb;25(2):544-51. doi: 10.1093/humrep/dep399. Epub 2009 Nov 12. PMID 19910321
• Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005 Oct 25;112(17):2735-52. doi: PMID 16157765
• Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metaboli PMID 19805654
• Teede HJ, Misso ML, Deeks AA, Moran LJ, Stuckey BG, Wong JL, Norman RJ, Costello MF; Guideline Development Groups. Assessment and management of polycystic ovary syndrome: summary of an evidence-based guideline. Med J Aust. 2011 Sep 19;195(6):S65-112. doi: 10.5694/mja11.10915. No abstract available. PMID 21929505
• Croze ML, Soulage CO. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013 Oct;95(10):1811-27. doi: 10.1016/j.biochi.2013.05.011. Epub 2013 Jun 10. PMID 23764390

Identifiers

NCT: NCT07747909 · KMU/DIR/CTU/2026/09

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗