The HMG-CoA reductase inhibitor simvastatin suppresses human testicular testosterone synthesis in vitro by a selective inhibitory effect on 17-ketosteroid-oxidoreductase enzyme activity

doi:10.1016/0960-0760(91)90333-Z

The Journal of Steroid Biochemistry and Molecular Biology

Volume 38, Issue 4, April 1991, Pages 465-468

https://doi.org/10.1016/0960-0760(91)90333-Z Get rights and content

Abstract

In concentrations probably exceeding those achieved in vivo, the cholesterol lowering compound simvastatin was found to suppress the synthesis of the androgens androstenediol and testosterone in vitro by human testicular homogenates. It was demonstrated that simvastatin in addition to its known inhibitory effect on HMG-CoA reductase activity, also affects the later steps of testicular steroidogenesis by selectively inhibiting the 17-ketosteroid-oxidoreductase catalyzed conversion of dehydroepiandrosterone and androstenedione to androstenediol and testosterone respectively. There was no effect of simvastatin on the Cytochrome P-450-dependent microsomal enzymes. Although in doses conventionally used in the treatment of hypercholesterolemia, simvastatin does not affect testicular steroidogenesis, at higher doses—especially when inadvertently administered during early pregnancy—adverse effects on normal testosterone biosynthesis and thereby fetal development should be considered.

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A third mechanism is by directly inhibiting other enzymes in the testosterone biosynthesis pathway (de Keyser et al., 2015). In particular, this mechanism involves the later steps of testicular steroidogenesis by selectively inhibiting the 17-ketosteroid-oxidoreductase-catalyzed conversion of dehydroepiandrosterone (DHEA) and androstenedione to androstenediol and testosterone, respectively (Smals et al., 1991). Interestingly, there are results indicating that low endogenous progesterone and, to a certain extent, dehydroepiandrosterone-sulfate (DHEA-S) levels, but not increased levels of endogenous testosterone, might represent risk factors for atherosclerotic microangiopathy in men (Tedeschi-Reiner et al., 2009).
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The HMG-CoA reductase inhibitor simvastatin suppresses human testicular testosterone synthesis in vitro by a selective inhibitory effect on 17-ketosteroid-oxidoreductase enzyme activity

Abstract

Cholesterol lowering effect of mevinolin, an inhibitor of 3 hydroxy-3-methylglutaryl-coenzyme A reductase in healthy volunteers

J. Clin. Invest.

HMG-CoA reductase inhibitor for treatment of hypercholesterolemia

New Engl. J. Med.

Andrenocortical function in type II hyperlipoproteinemic patients treated with lovastatin (mevinolin)

Horm. Metab. Res.

The effect of mevinolin on steroidogenesis in patients with defectsnin the low density lipoprotein receptor

J. Clin. Endocr. Metab.

Gonadal and adrenal function during long-term treatment with a new HMG-CoA reductase inhibitor

Clin. Res.