Effects of Metformin Plus Simvastatin on Polycystic Ovarian Syndrome (PCOS): A Prospective, Randomized, Double-Blind, Placebo-Controlled Study
Condition: Polycystic Ovary Syndrome
MeSH terms: Polycystic Ovary Syndrome; Syndrome
Study type: Interventional
Phase: Phase 4

Summary: 
      Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting 6.5%-6.7% of women in
      reproductive age, and is commonly associated with obesity, menstrual irregularity, insulin
      resistance (IR), infertility, and clinical hyperandrogenism and/or hyperandrogenemia (1,2).
      PCOS is also associated with increased risk of abnormal lipoproteins and hypertension, as
      well as cardiovascular or cerebrovascular morbidity (3). The lipid and lipoprotein profile in
      androgenized women with poly cystic ovaries is similar to the made pattern with higher levels
      of cholesterol, low-density lipoprotein (LDL), and lower levels of high-density lipoprotein
      (HDL), and this abnormal pattern is independent of body weight (4). Insulin resistance is
      associated with reproductive abnormalities in women with PCOS. Improving insulin sensitivity
      through both lifestyle and pharmacological intervention can ameliorate these abnormalities.
      Insulin resistance in women with PCOS is common (up to 50%), both in obese and nonobese women
      (5), and disordered insulin action precedes the increase in androgen.

      Treatment for PCOS subjects typically includes, implementation of lifestyle changes
      especially weight loss and adjuvant pharmaceutical intervention including oral
      contraceptives, anti-androgen therapy and insulin-lowering drugs (such as, metformin) (6).
      Metformin is a biguanide used extensively in type 2 diabetes. It inhibits hepatic glucose
      production and increases peripheral insulin sensitivity, but dose not cause hypoglycemia.
      Several studies have shown an increase in insulin sensitivity and pregnancy rate accompanied
      by decreased insulin and androgen levels in PCOS patients taking metformin (7).

      The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-COA) reductase inhibitors (statins) are the
      rate-limiting step in cholesterol biosynthesis, and inhibition of this enzyme decreases
      cholesterol synthesis and a compensatory increase in the expression of LDL receptors in the
      liver. Statins reduce plasma triglycerides in dose-dependent fashion and also have a modest
      HDL-raising effect which is not dose-dependent (8,9). Furthermore, statins pose other
      cardio-protective properties, including antioxidant and anti-inflammatory actions (10,11).

      Some studies have reported that simvastatin decreases serum androgen levels in women with
      PCOS (12,13) by inhibiting proliferation and steroidogenesis of ovarian theca-interstitial
      cells (14). According to these previous findings, we hypothesized that combination therapy
      with simvastatin and metformin will result in lower androgen levels and cardiovascular risk
      factors in women with PCOS.
    


Intervention name(s): Metformin plus Placebo; Metfomin plus Simvastatin
Intervention type(s): Drug; Drug
Intervention description(s): PCOS patients(n=42) will be assigned to the placebo (once/day) plus metformin (500mg three times a day, n=42; group 2)
Intervention MeSH terms: Metformin; Simvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Polycystic ovary syndrome; Metformin; Simvastatin