Polycystic Ovary Syndrome
Conditions
Keywords
PCOS
Brief 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.
Interventions
DRUGRosiglitazone
4 mg twice daily for 8 weeks orally
DRUGAcarbose
100 mg three times daily for 8 weeks orally
Sponsors
Canadian Institutes of Health Research (CIHR)
Jean-Patrice Baillargeon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Androgen hyper-responsiveness to insulin - Ratio | 8 weeks | The calculated ratio of free testosterone to the area under the insulin curve during an OGTT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Androgen hyper-responsiveness to insulin - Relationship | 8 weeks | Determined by the relationship between testosterone and insulin levels during an OGTT. |
| Insulin sensitivity | 8 weeks | Determined by a 2-step insulin-glucose clamp |
| Insulin secretion | 8 weeks | Determined by a 2-step insulin-glucose clamp |
| Hepatic glucose production | 8 weeks | Determined by a 2-step insulin-glucose clamp |
| Plasma DCI-IPG during euglycemic-hyperinsulinemic clamp | 8 weeks | Measured during steady-state |
Countries
Canada
Outcome results
None listed