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

18 Years
40 Years
Open (Enrolling)
Polycystic Ovary Syndrome

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Trial Information

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

Polycystic ovary syndrome (PCOS) is a very common but complex endocrine disorder affecting 6
to 10% of childbearing age women. To diagnose PCOS, women must display two of these three
symptoms: clinical or biochemical hyperandrogenism, oligoamenorrhea, and/or echographycally
confirmed polycystic ovary. Many studies have also demonstrated that PCOS women are more
insulin resistant than control women when matched for body mass index (BMI). Thus, insulin
resistance (IR) and secondary hyperinsulinemia would be important premises in the
development of PCOS. In fact, the prevalence of type 2 diabetes (T2D) is tripled in PCOS

Higher free fatty acid (FFA) concentrations were also observed in the circulation of PCOS
women. As FFA accumulates in liver and muscle instead of fat cells, this could be an
important cause of IR according to the theory of lipotoxicity. Some indirect evidences are
suggesting that FFA accumulation in androgen secreting cells (ovary and adrenal gland) could
enhance their androgen production. Based on these findings, our hypothesis is that FFA
accumulation in non fatty tissues would lead to IR 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 PCOS women
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.

Inclusion Criteria:


- 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

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science

Outcome Measure:

Androgen hyper-responsiveness to insulin, as determined by the relationship between testosterone and insulin levels (or the ratio of free testosterone to the area under the insulin curve) during an OGTT and 24h urinary clearance of DCI in PCOS women

Outcome Time Frame:

5 years

Safety Issue:


Principal Investigator

Jean-Patrice Baillargeon, MD, MSc

Investigator Role:

Principal Investigator

Investigator Affiliation:

Universitaire de Sherbrooke


Canada: Health Canada

Study ID:




Start Date:

August 2006

Completion Date:

September 2011

Related Keywords:

  • Polycystic Ovary Syndrome
  • PCOS
  • Polycystic Ovary Syndrome
  • Hyperandrogenism