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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.
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.
Allocation: Randomized, Control: Active Control, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science
Polycystic Ovary Syndrome
Université de Sherbrooke
Universitaire de Sherbrooke
Published on BioPortfolio: 2014-08-27T03:17:45-0400
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A complex disorder characterized by infertility, HIRSUTISM; OBESITY; and various menstrual disturbances such as OLIGOMENORRHEA; AMENORRHEA; ANOVULATION. Polycystic ovary syndrome is usually associated with bilateral enlarged ovaries studded with atretic follicles, not with cysts. The term, polycystic ovary, is misleading.
A condition caused by the excessive secretion of ANDROGENS from the ADRENAL CORTEX; the OVARIES; or the TESTES. The clinical significance in males is negligible. In women, the common manifestations are HIRSUTISM and VIRILISM as seen in patients with POLYCYSTIC OVARY SYNDROME and ADRENOCORTICAL HYPERFUNCTION.
A complication of OVULATION INDUCTION in infertility treatment. It is graded by the severity of symptoms which include OVARY enlargement, multiple OVARIAN FOLLICLES; OVARIAN CYSTS; ASCITES; and generalized EDEMA. The full-blown syndrome may lead to RENAL FAILURE, respiratory distress, and even DEATH. Increased capillary permeability is caused by the vasoactive substances, such as VASCULAR ENDOTHELIAL GROWTH FACTORS, secreted by the overly-stimulated OVARIES.
An inhibitor of alpha glucosidase that retards the digestion and absorption of carbohydrates in the small intestine and hence reduces the increase in blood-glucose concentrations after a carbohydrate load. It is given orally to non-insulin dependent diabetes mellitus patients where diet modification or oral hypoglycemic agents do not control their condition. (From Martindale The Extra Pharmacopoeia, 31st ed)
A rare condition of sexual ambiguity in which the individual possesses gonadal tissues of both SEXES, tissues from the OVARY and the TESTIS. There can be a testis on one side and an ovary on the other (lateral), or there may be combined ovarian and testicular tissue (ovotestes) on each side (bilateral). Most common karyotype is 46,XX. Others include 46,XY and 45,X/XY.
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