Role of Insulin Action and Free Fatty Acids in Hyperandrogenism of Women With Polycystic Ovary Syndrome
Condition: Polycystic Ovary Syndrome
MeSH terms: Polycystic Ovary Syndrome; Hyperandrogenism; Syndrome
Study type: Interventional

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.
    

Detailed description: 
      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 women.

      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.
    

Intervention name(s): Rosiglitazone; Acarbose
Intervention type(s): Drug; Drug
Intervention description(s): 4 mg twice daily for 8 weeks orally; 100 mg three times daily for 8 weeks orally
Other intervention name(s): Avandia; Prandase
Intervention MeSH terms: Rosiglitazone; Acarbose
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: PCOS