Role of Insulin Action and Free Fatty Acids in Hyperandrogenism of Women With Polycystic Ovary Syndrome

• Status: Suspended
• Trial end date: 2021-10-01
• Target enrollment: 0
• Participant gender: Female

Summary

The investigators hypothesis is that free fatty acids (FFA) accumulation in non fatty tissues would lead to insulin resistance and hyperandrogenism in PCOS women. Accordingly, Peroxisome Proliferator-Activated Receptor gamma (PPARγ) agonist (rosiglitazone) would be a great therapeutic option for PCOS as their activation induces transcription factors of gene implicated in fatty acids metabolism.

The aim is to verify if insulin-related hyperandrogenism can be reversed in women having polycystic ovary syndrome following an 8-week treatment with rosiglitazone compared to simple insulin reduction with acarbose.

For the purpose of this study, 14 lean women (BMI ≤ 25 kg/m2) and 36 obese women (BMI 30-39 kg/m2) with PCOS as well as 14 lean and 14 obese control women will be recruited to determine their insulin sensibility (insulin levels, M-value, metabolic clearance rate of glucose)and FFA metabolism (FFA levels, rythm of apparition and disapearance of FFA) during a 75g oral glucose tolerance test and a 2-step insulin-glucose clamp.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Jean-Patrice Baillargeon
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Treatments: Acarbose; Insulin; Rosiglitazone

Criteria

Inclusion Criteria:

PCOS :

• Biochemical hyperandrogenism (free testosterone ≥ 50 pmol/l)

• Oligomenorhea (≤ 8 menstrual cycle per year)

Health volunteers :

• Normal menstrual cycle

• Normal levels of free and total testosterone

• No family history with PCOS

Exclusion Criteria:

• Diabetes or glucose intolerance

• Current or past use within 3 months of oral contraceptives

• Current or past use within 3 months of medications known to affect insulin sensitivity (metformin, PPARy agonists, b-blockers, thiazides, calcium channel blockers, glucocorticoids, etc.)

• Pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious or neoplastic disease (other than non-melanoma skin cancer)

• Documented or suspected recent (within one year) history of drug abuse or alcoholism

• Use of any investigational drug within three months prior to study onset

Healthy volunteers :

• History of gestational diabetes

• Positive family history for first-degree relative with diabetes

• Disorders linked to insulin resistance (hypertension, dyslipidemia or acanthosis nigricans)