In a narrative review published in Medicina, researchers presented a comprehensive overview of the existing literature on the application of statins in the treatment of polycystic ovary syndrome (PCOS), a common hormone problem affecting women of childbearing age.
They reviewed the available evidence on the multifactorial pathogenesis of androgen excess and dyslipidemia in women with PCOS, which helped them understand the complex interactions between statins and PCOS endocrine dynamics.
Study: The Current and Emerging Role of Statins in the Treatment of PCOS: The Evidence to Date. Image Credit: MMD Creative/Shutterstock.com
Background
PCOS has several cardinal features, of which polycystic ovaries, androgen excess, varying degrees of hyperandrogenism, i.e., excess production of “male” hormones, and an adverse metabolic risk profile are most notable as they drive diverse clinical manifestations.
For instance, affecting ~60-80% of PCOS women, hyperandrogenism and androgen excess often clinically manifest as hirsutism, severe acne, and androgenic alopecia.
Excess testosterone in a female body worsens central adiposity; additionally, it alters the luteinizing hormone (LH) /follicle-stimulating hormone (FSH) ratio upon conversion to estrone, which may cause menstrual irregularities and, in worst cases, infertility.
The risk of metabolic aberrations (e.g., obesity, insulin resistance [IR], dyslipidemia) is also higher in PCOS patients. Thus, they are prone to developing type 2 diabetes (T2D), coronary heart disease, and stroke.
Furthermore, up to 70% of PCOS patients have dyslipidemia. Hence, lipid profiling of women with PCOS should be part of the routine PCOS management, with suggested screening frequency every two years.
This test quantifies serum levels of low-density lipoprotein (LDL) and triglycerides (TG), high-density lipoprotein (HDL), and total cholesterol (TC).
Statins for PCOS management
Statins, lipid-lowering drugs, are also known as hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors.
Studies have investigated whether statins can reduce androgen excess in PCOS patients. In this regard, three recent studies are notable. First is a meta-analysis investigating the effects of statins alone or in conjunction with metformin in women with PCOS.
Its findings pointed out a marked decline in androstenedione, dehydroepiandrosterone (DHEA), hormones secreted by the adrenal gland and ovaries, total testosterone, free testosterone, prolactin, and LH, LH/FSH ratio in the statin recipients.
Statin use also markedly decreased their TC, LDL cholesterol, TG, insulin sensitivity index, fasting glucose, and C-reactive protein (CRP).
Another meta-analysis also demonstrated comparable beneficial effects of statins in PCOS patients when used in conjunction with metformin.
Furthermore, studies have compared the effects of different types of statins in women with PCOS. For instance, a randomized crossover trial in 48 PCOS patients found that simvastatin, a type of statin, when used with an oral contraceptive, showed additional beneficial effects in lowering androgens and improving the systemic inflammation markers and lipid profile.
Regarding their mechanisms of action in PCOS, studies have revealed that statins interfere with different steps of its pathophysiology. The most notable is their ability to inhibit the mevalonate pathway, which is highly beneficial in PCOS.
Further, statins reduce cholesterol synthesis in PCOS patients, which decreases its availability, which, in turn, protects the ovaries from excessive levels of insulin and insulin-like growth factor 1.
Other mechanisms utilized by statins to combat hypercholesterolemia were increasing LDL receptor expression, reducing cholesterol absorption in the gut, and decreasing the production of oxidative and inflammatory compounds.
Statins also showed the potential to reduce the proliferation of theca-interstitial cells and suppress receptors of advanced glycation end products (AGEs) to disrupt steroidogenesis in PCOS, leading to decreased androgen levels.
Conclusion and future perspective
Statin use in PCOS cases exhibited varied effects across studies; nonetheless, their cardiometabolic benefits significantly outweighed the associated risks.
Besides, statins were beneficial in treating hyperandrogenemia, which makes them a promising treatment regimen for some PCOS patients.
However, as their use may raise the risk of possible teratogenicity in PCOS women who are pregnant, more concrete evidence from clinical studies with larger samples in different PCOS phenotypes and disease stages is needed. In addition, statins-associated other side effects, such as myalgia, need to be addressed.
Even though current research into the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on the endocrine system remains scarce, they, too, have significant cholesterol-lowering potential like statins, which may help mitigate cardiovascular risk in PCOS patients.
In murine models of PCOS, PCSK9 modulators alleviated lipid metabolism disorders, serum reproductive hormones, and other pathological changes in ovaries, opening avenues for their future use in PCOS women to improve metabolic profile and hyperandrogenism.
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