CONTEXT: Polycystic ovary syndrome (PCOS) is associated with increased risk of cardiovascular morbidity, whereas statins are proven to reduce cardiovascular mortality and morbidity through lipid-lowering and perhaps through their pleiotropic effects. Statins can also reduce testosterone in vitro by inhibiting ovarian theca-interstitial cell proliferation and steroidogenesis and reducing inflammation in vivo. OBJECTIVE: Our objective was to assess the effect of atorvastatin on inflammatory markers, insulin resistance, and biochemical hyperandrogenemia in patients with PCOS. DESIGN AND SETTING: We conducted a randomized, double-blind, placebo-controlled study at a tertiary care setting in United Kingdom. PATIENTS: Patients included 40 medication-naive patients with PCOS and biochemical hyperandrogenemia. METHODS: Patients were randomized to either atorvastatin 20 mg daily or placebo. MAIN OUTCOME MEASURES: The primary endpoint of the study was a change in the inflammatory marker high-sensitivity C-reactive protein. The secondary endpoints were a change in insulin resistance and total testosterone. RESULTS: After 12 wk atorvastatin, there was a significant reduction (mean +/- sem) in total cholesterol (4.6 +/- 0.2 vs. 3.4 +/- 0.2 mmol/liter, P < 0.01), low-density lipoprotein cholesterol (2.9 +/- 0.2 vs. 1.8 +/- 0.2 mmol/liter, P < 0.01), triglycerides (1.34 +/- 0.08 vs. 1.08 +/- 0.13 mmol/liter, P <0.01), high-sensitivity C-reactive protein (4.9 +/- 1.4 vs. 3.4 +/- 1.1 mg/liter, P = 0.04), free androgen index (13.4 +/- 0.6 vs. 8.7 +/- 0.4, P < 0.01), testosterone (4.1 +/- 0.2 vs. 2.9 +/- 0.1 nmol/liter, P < 0.01) and insulin resistance as measured by homeostasis model assessment for insulin resistance (HOMA-IR) (3.3 +/- 0.4 vs. 2.7 +/- 0.4). There was a significant increase in SHBG (31.1 +/- 1.0 vs. 35.3 +/- 1.2 nmol/liter, P < 0.01). There was a positive correlation between the reduction in HOMA-IR in the atorvastatin group with the reduction in triglycerides and the reduction of free androgen index. There was a significant deterioration of HOMA-IR in the placebo group (3.0 +/- 0.4 vs. 3.8 +/- 0.5). CONCLUSIONS: This study suggests that atorvastatin is effective in reducing inflammation, biochemical hyperandrogenemia, and metabolic parameters in patients with PCOS after a 12-wk period.
RCT Entities:
CONTEXT: Polycystic ovary syndrome (PCOS) is associated with increased risk of cardiovascular morbidity, whereas statins are proven to reduce cardiovascular mortality and morbidity through lipid-lowering and perhaps through their pleiotropic effects. Statins can also reduce testosterone in vitro by inhibiting ovarian theca-interstitial cell proliferation and steroidogenesis and reducing inflammation in vivo. OBJECTIVE: Our objective was to assess the effect of atorvastatin on inflammatory markers, insulin resistance, and biochemical hyperandrogenemia in patients with PCOS. DESIGN AND SETTING: We conducted a randomized, double-blind, placebo-controlled study at a tertiary care setting in United Kingdom. PATIENTS: Patients included 40 medication-naive patients with PCOS and biochemical hyperandrogenemia. METHODS:Patients were randomized to either atorvastatin 20 mg daily or placebo. MAIN OUTCOME MEASURES: The primary endpoint of the study was a change in the inflammatory marker high-sensitivity C-reactive protein. The secondary endpoints were a change in insulin resistance and total testosterone. RESULTS: After 12 wk atorvastatin, there was a significant reduction (mean +/- sem) in total cholesterol (4.6 +/- 0.2 vs. 3.4 +/- 0.2 mmol/liter, P < 0.01), low-density lipoprotein cholesterol (2.9 +/- 0.2 vs. 1.8 +/- 0.2 mmol/liter, P < 0.01), triglycerides (1.34 +/- 0.08 vs. 1.08 +/- 0.13 mmol/liter, P <0.01), high-sensitivity C-reactive protein (4.9 +/- 1.4 vs. 3.4 +/- 1.1 mg/liter, P = 0.04), free androgen index (13.4 +/- 0.6 vs. 8.7 +/- 0.4, P < 0.01), testosterone (4.1 +/- 0.2 vs. 2.9 +/- 0.1 nmol/liter, P < 0.01) and insulin resistance as measured by homeostasis model assessment for insulin resistance (HOMA-IR) (3.3 +/- 0.4 vs. 2.7 +/- 0.4). There was a significant increase in SHBG (31.1 +/- 1.0 vs. 35.3 +/- 1.2 nmol/liter, P < 0.01). There was a positive correlation between the reduction in HOMA-IR in the atorvastatin group with the reduction in triglycerides and the reduction of free androgen index. There was a significant deterioration of HOMA-IR in the placebo group (3.0 +/- 0.4 vs. 3.8 +/- 0.5). CONCLUSIONS: This study suggests that atorvastatin is effective in reducing inflammation, biochemical hyperandrogenemia, and metabolic parameters in patients with PCOS after a 12-wk period.
Authors: Selma F Witchel; Sergio E Recabarren; Frank González; Evanthia Diamanti-Kandarakis; Kai I Cheang; Antoni J Duleba; Richard S Legro; Roy Homburg; Renato Pasquali; Rogerio A Lobo; Christos C Zouboulis; Fahrettin Kelestimur; Franca Fruzzetti; Walter Futterweit; Robert J Norman; David H Abbott Journal: Endocrine Date: 2012-06-04 Impact factor: 3.633
Authors: Israel Ortega; Amanda B Cress; Donna H Wong; Jesus A Villanueva; Anna Sokalska; Ben C Moeller; Scott D Stanley; Antoni J Duleba Journal: Biol Reprod Date: 2012-01-30 Impact factor: 4.285
Authors: Izabela J Rzepczynska; Piotr C Piotrowski; Donna H Wong; Amanda B Cress; Jesus Villanueva; Antoni J Duleba Journal: Biol Reprod Date: 2009-07-01 Impact factor: 4.285