Role of Semaglutide in Restoring Ovulation in Youth and Adults With Polycystic Ovary Syndrome

Study Overview
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Brief Summary
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Girls and women 12-35 years old with obesity and polycystic ovarian syndrome who are on or off metformin, will receive a glucagon like peptide-1 receptor agonist intervention for 10 months to induce metabolic changes, weight loss and improve reproductive abnormalities.

Detailed Description
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Polycystic ovary syndrome is one of the most common endocrinopathies in women, presents with anovulation in adolescence, and reproductive dysfunction is related to excess weight. After a 4-month observation period of either no medication or metformin treatment, females aged 12-35 years with obesity and polycystic ovary syndrome will receive 10 months of a glucagon-like peptide-1 receptor agonist to induce metabolic changes, weight loss and improve reproductive abnormalities. We will assess the relationship between weight loss and reproductive function, as well as identify if age, hormonal and metabolic measures and such insulin sensitivity and insulin secretion predict the response to glucagon-like peptide-1 receptor agonist therapy.

Official Title
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Role of Semaglutide in Restoring Ovulation in Youth and Adults With Polycystic Ovary Syndrome

Conditions
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PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries, Obese

Intervention / Treatment
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* Drug: Wegovy Injectable Product
* Drug: Metformin and Wegovy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Female Ages 12-35 years Sedentary- less than 2 hours of moderate (jogging, swimming etc.) exercise a week. Oligomenorrhea, on or off metformin, as defined per age category in the most recent 2018 PCOS international guidelines Initial BMI based on age and weight: If <18 years, initial BMI percentile ≥95 If 18-35 years, initial BMI ≥30 kg/m2 OR initial BMI ≥27 kg/m2 with at least one weight-related comorbid condition, e.g., hypertension or dyslipidemia Must be weight stable within ±5kg in the 3 months prior to enrollment Diagnosed with PCOS per the most stringent NIH criteria with adaptation for adolescents (oligomenorrhea >24 months post-menarche or primary amenorrhea after age 15 years and clinical/ biochemical hypertestosteronemia Participants cannot be on hormonal contraception, so participants should remain abstinent or use reliable non-hormonal contraception (e.g., copper IUD) for the entire study period. For participants who receive semaglutide, they should avoid pregnancy for at least 2 months after stopping medication to avoid fetal exposure to the medication. For participants in the metformin + semaglutide group, participants must have been stable on ≥ 1500 mg of metformin a day for at least 3 months by time of screening Exclusion Criteria: Diagnosed with or have a family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2). Family history of medullary thyroid cancer or thyroid nodule palpated by endocrinologist at screening. - Per approved drug label Use of medications known to affect insulin sensitivity: metformin (cannot have been used in the 3 months prior to screening for the untreated arm of the study), chronic oral steroids, oral glucocorticoids within 10 days, atypical antipsychotics, immunosuppressant agents, HIV medications, estrogen-containing hormonal contraception (cannot have been used in the 6 months prior to screening), progesterone-containing hormonal contraception (cannot have been used in the 3 months prior to screening). Dermal patch or vaginal ring contraception methods. Weight loss medications or stimulants. Use of other products containing other GLP-1 agonists. Weight loss medications in the last 6 months Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study. Severe illness requiring hospitalization within 60 days. Diabetes, defined as Hemoglobin A1C ≥6.5% Anemia, defined as Hemoglobin < 12 mg/dL Diagnosed major psychiatric or developmental disorder limiting informed consent. 10) Known liver disease other than NAFLD, or AST or ALT >125 IU/L. 11) Personal history of pancreatitis 12) Known renal disease of any severity or an eGFR at screening of <45ml/min/1.73m2 13) History of severe GI disease (e.g., gastroparesis) 14) History of gallstones 15) Untreated thyroid disease 16) History of hypersensitivity to semaglutide 17) Other causes of hyperandrogenism (example: tumor, CAH) or amenorrhea (untreated thyroid disease, tumor, primary ovarian failure, prolactinoma). 18) Active symptoms or undergoing treatment for anorexia nervosa or binging/purging disorder 19) Desiring pregnancy in the next 12-18 months. 20) Bariatric surgery

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin + Semaglutide<br>Participants with PCOS who are currently on metformin and still not having regular menses, will receive 10-months of semaglutide intervention | Drug: Metformin and Wegovy<br>* Participants already on Metformin as part of their clinical care, and still having irregular periods will be enrolled in the Metformin and Semaglutide arm. Semaglutide will be added in addition to the Metformin they are currently taking. 10 months of semaglutide, with dose escalation as recommended by manufacturer. Maximum dose used will be 1.7mg<br>* Other names: Glucophage and Semaglutide;|
| Experimental: Semaglutide<br>Participants with PCOS who are not on metformin or hormonal therapy, will receive 10-months of semaglutide intervention | Drug: Wegovy Injectable Product<br>* 10 months of semaglutide, with dose escalation as recommended by manufacturer. Maximum dose used will be 1.7mg<br>* Other names: Semaglutide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of ovulation | Number of ovulations as assessed by urinary progesterone in 4 month before and during treatment | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCOS, semaglutide