Patients receiving statins have lower levels of sex hormone-binding globulin (SHBG) and dehydroepiandrosterone (DHEA), according to study results published in The Journal of Clinical Endocrinology & Metabolism.

Considering more individuals are eligible for statin therapy based on the 2018 American College of Cardiology/American Heart Association cholesterol guidelines, it is important to examine the possibility that the inhibition of cholesterol biosynthesis may impair gonadal steroidogenesis. This large epidemiologic study was designed to evaluate the impact of statin therapy on endogenous sex hormones.

A total of 6814 participants were included in the Multi-Ethnic Study of Atherosclerosis cohort, a population-based study of individuals aged 45 to 84 years recruited from Baltimore, Maryland; Chicago, Illinois; Forsyth County, North Carolina; Los Angeles County, California; northern Manhattan, New York; and Saint Paul, Minnesota, from 2000 to 2002. Of these participants, 6171 had serum sex hormone measurements available for DHEA, estradiol, SHBG, and total and bioavailable testosterone (T). Among participants who were statin users (n = 809; mean age, 67 years; 57% men), 41% were white, 29% were black, 19% were Hispanic, and 11% were Chinese. The relationship of statin therapy to each sex hormone was assessed using multivariable linear regression models.

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After multivariate adjustment, total T in men and DHEA and SHBG in both men and postmenopausal women were all inversely associated with statin use (P <.05). Compared with participants who did not use statins, mean SHBG was 3.54 nmol/L lower in women (P <.01) and 3.37 nmol/L lower in men (P <.001) who used statins, or approximately one-fifth of a standard deviation lower. Mean DHEA was 1.06 nmol/L lower in women (P <.05) and 0.70 nmol/L lower in men (P <.01), or approximately one-tenth of a standard deviation lower. Total T in male statin users compared with male nonusers was 0.81 nmol/L lower (P <.05).

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After further propensity score adjustment, mean levels of DHEA and SHBG in statin users compared with nonusers were 0.67 nmol/L (P <.05) and 3.47 nmol/L (P <.001) lower, respectively. No association remained between total T of male statin users compared with male nonusers.

Study investigators concluded, “SHBG and DHEA in both men and women were inversely associated with statin use. These changes give insight into other pathways being affected by statins and may necessitate monitoring of sex hormone levels with statin therapy. Further prospective studies or clinical trials will be relevant to elucidate this.”

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Oluleye OW, Kronmal RA, Folsom RA, et al. Association between statin use and sex hormone in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort [published online June 3, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2019-00530