The Effect of Statins on Levels of Dehydroepiandrosterone (DHEA) in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Abstract

BackgroundCurrently, statins are used to treat polycystic ovary syndrome (PCOS). This systematic review and meta-analysis aimed to investigate the effect of statins on serum or plasma levels of dehydroepiandrosterone (DHEA) in women with PCOS.Material/MethodsDatabases that were searched included PubMed, Embase, and the Cochrane Library from their inception to August of 2018. Published randomized controlled trials (RCTs) were identified that evaluated the impact of statins on plasma DHEA levels in women with PCOS. The Cochrane risk of bias tool was used to assess the quality of the included RCTs. A random-effects model was used to analyze the pooled results.ResultsMeta-analysis was performed on data from ten published studies that included 735 patients and showed that statin treatment could significantly reduce plasma DHEA levels when compared with controls (SMD, −0.43; 95% CI, −0.81–0.06; p=0.02; I2=82%). Statins were significantly more effective than placebo in reducing the levels of DHEAs. Subgroup analysis based on statin type showed that atorvastatin significantly reduced DHEA levels (SMD, −0.63; 95% CI, −1.20 – −0.05; p=0.03; I2=38%) but simvastatin did not significantly reduce DHEA levels (SMD: −0.14; 95% CI, −0.49–0.28; p=0.43; I2=77%). Subgroup analysis based on duration of treatment showed no significant difference between 12 weeks of statin treatment (SMD, −0.61; 95% CI, −1.23–0.02; p=0.06; I2=85%) and 24 weeks (SMD, −0.34; 95% CI −0.95–0.28; p=0.29; I2=83%).ConclusionsMeta-analysis showed that statins significantly reduced the levels of DHEA when compared with placebo in patients with PCOS.

The effects of statins on hyperandrogenism in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials

“…Years ago, two reviews employed few RCTs and implied a positive effect of statin treatment reducing testosterone and DHEA levels of PCOS women [ 28 , 29 ]. Now, more RCTs included in our meta-analysis made this conclusion solid.…”

“…Ten years ago, a meta-analysis, based on 3 original trials, suggested that statins could reduce testosterone levels in PCOS, but the testosterone levels were not assigned as the primary outcome, and the bias of the trials and stability of the results were not assessed [ 28 ]. Another meta-analysis [ 29 ] reported that statins could reduce the DHEA levels in PCOS, but it included a nonrandom study [ 30 ] in the pooled studies, which limited the reliability of the conclusion. Additionally, those meta-analyses did not pay attention to assessing the effect of statins on the clinical manifestations associated with hyperandrogenism.…”

Comparative efficacy of statins, metformin, spironolactone and combined oral contraceptives in reducing testosterone levels in women with polycystic ovary syndrome: a network meta-analysis of randomized clinical trials

“…The study found that atorvastatin provided a greater reduction in testosterone levels in patients with PCOS when compared to COC, spironolactone plus metformin, simvastatin, spironolactone, simvastatin plus metformin, metformin, lifestyle modification, and placebo, respectively. The pros and cons of atorvastatin use in improving PCOS symptoms have been addressed in the literature [17][18][19]. It has been shown that using atorvastatin for a duration of more than 12 weeks had substantially improved PCOS symptoms [17], yet, it impairs insulin sensitivity [18].…”

“…The pros and cons of atorvastatin use in improving PCOS symptoms have been addressed in the literature [17][18][19]. It has been shown that using atorvastatin for a duration of more than 12 weeks had substantially improved PCOS symptoms [17], yet, it impairs insulin sensitivity [18]. However, to our knowledge, this is the first study to compare between atorvastatin and all interventions in terms of reducing the testosterone level in patients with PCOS.…”

The Utilization of Dehydroepiandrosterone as a Sexual Hormone Precursor in Premenopausal and Postmenopausal Women: An Overview

“…In other words, women with PCOS commonly have insulin-resistance with hyperinsulinemia, as well as increased risk of impaired glucose tolerance and type 2 diabetes mellitus. However, a population-based, prospective cohort study showed that reduced levels of serum DHEA increase the risk of type 2 diabetes, due to the possible mechanism in increasing glucose uptake after the stimulation of GLUT4 and GLUT1 translocation to the plasma membrane [49]. As mentioned above, DHEA has the ability to inhibit oxidative stress, activate PKC, and activate phosphatidylinositol 3-kinase (PI3-kinase) to improve glucose uptake and improve endothelial function.…”