An investigation into the therapeutic effects of statins with metformin on polycystic ovary syndrome: a meta-analysis of randomised controlled trials

Abstract

ObjectivesTo investigate the therapeutic effects of statins with metformin on polycystic ovary syndrome (PCOS).SettingsEndocrinology department.ParticipantsMEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched until October 2014. Studies comparing statins and placebo, as well as the combination of statins and metformin and metformin alone, were included in the analysis.InterventionsData were independently extracted by two researchers; any convergence was resolved by a third reviewer.Primary and secondary outcome measuresThe following properties were extracted from the qualified trials to identify the effects of statins: clinical variables, metabolic characteristics, hormone outcomes, sign of inflammation, glucose parameters and insulin outcomes.ResultsData from four trials comparing statin and metformin with metformin alone were analysed. The combination of statins and metformin decreases the levels of C reactive protein (standardised mean difference (SMD) −0.91; 95% CI −1.81 to −0.02; p=0.046), triglyceride (SMD −1.37; 95% CI −2.46 to −0.28; p=0.014), total cholesterol (SMD −1.28; 95% CI −1.59 to −0.97; p=0.000) and low-density lipoprotein (LDL) cholesterol (SMD −0.74; 95% CI −1.03 to −0.44; p=0.000). However, the combined therapy fails to reduce fasting insulin (SMD −0.92; 95% CI −2.07 to 0.24; p=0.120), homeostasis model assessment of insulin resistance (SMD −1.15; 95% CI −3.36 to 1.06; p=0.309) and total testosterone (SMD −1.12; 95% CI −2.29 to 0.05; p=0.061). Analysis of the five trials comparing statin with placebo shows that statin monotherapy reduces LDL-cholesterol, triglyceride and total cholesterol.ConclusionsCombined statin and metformin therapy can improve lipid and inflammation parameters, but cannot effectively improve insulin sensitivity and reduce hyperandrogenism in women with PCOS. A large-scale randomised controlled study must be conducted to ascertain the long-term effects of the therapy.

Pharmacological and surgical treatment of nonreproductive outcomes in polycystic ovary syndrome: An overview of systematic reviews

“…Seven reviews (n = 3 comparing metformin vs thiazolidinediones, n = 2 comparing metformin vs placebo, n = 1 comparing metformin vs COCPs and n = 1 comparing combination therapy with metformin and clomiphene citrate vs clomiphene citrate alone) reported results favouring metformin in terms of BMI and/or waist‐hip ratio. There was no significant difference in anthropometric outcomes when metformin was compared to acarbose or orlistat, or when combination therapy with metformin and statin was compared to metformin alone . Endocrine outcomes were assessed by 12 reviews.…”

“…The country of origin of the authors included China (n = 11), [29][30][31][32][33][34][35][36][37][38][39] Australia (n = 6), [40][41][42][43][44][45] United Kingdom (n = 5), 43,[45][46][47][48] the United States of America (n = 4), [49][50][51][52] India (n = 3), 44,52,53 Canada (n = 3), 50,54,55 Brazil (n = 2), 41,56 Iran (n = 2), 40,54 Columbia (n = 1), 46 Greece (n = 1), 57 Italy (n = 1), 57 Spain (n = 1), 58 Scotland (n = 1), 59 Luton (n = 1), 48 Netherlands (n = 1) 41 and Saudi Arabia (n = 1). 46 Thirteen reviews explicitly included randomized control trials (RCTs) only [29][30][31][32]34,36,38,42,43,…”

“…46 Thirteen reviews explicitly included randomized control trials (RCTs) only [29][30][31][32]34,36,38,42,43,46,53,57,59 ; 5 reviews included RCTs and phase-1 data of cross-over trials 39,41,44,45,52 ; 2 reviews included RCTs and prospective trials 50,56 ; 2 reviews included RCTs and observational studies 49,58 ; 1 review included RCTs, comparative studies and case series with >5 patients 55 ; 2 reviews included all clinical trials 40,54 ; 3 reviews included all study types 35,48,51 ; and 3 reviews did not state an inclusion criteria for the study type. 33,37,47 Fifteen reviews did not set a language restriction in their literature search 30,31,[39][40][41][43][44][45][46]49,50,52,[56][57][58] ; 11 reviews restricted their search to English publications only…”

“…1 review restricted its language to English and Persian 54 ; 1 review restricted its language to English and Chinese 33 ; and 3 reviews did not state if any language restriction was applied. 29,47,48 Twelve reviews reported following a guideline on good practice in conducting systematic reviews 30,31,35,39,41,[44][45][46][47]53,57,58 ; 25 reviews included metaanalyses [29][30][31][32][33][34][35][36][37][38][41][42][43][44][45][46][47][49][50][51][52][53][55][56][57] ; and 18 reviews did not provide a clear statement as to the overall quality assessment of the included articles. 31,33,34,36,37,[41][42][43]…”

Targets to treat metabolic syndrome in polycystic ovary syndrome

“…There are a few studies of statin therapy in women with PCOS with lipid abnormalities replicating this finding. [144,145] The additional benefits of statins include a reduction of ovarian androgen synthesis as noted by a study of atorvastatin on metabolic profile of women with PCOS. [146]…”