Effects of long-term simvastatin treatment on testicular and adrenal steroidogenesis in hypercholesterolemic patients

Abstract

Simvastatin is an inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, the key enzyme in the synthesis of cholesterol, recently introduced in the therapy of hypercholesterolemic patients. Cholesterol is the precursor of the biosynthesis of steroid hormones; thus, a reduction of the availability of cholesterol in the adrenal and testicular cells may reduce the synthesis of corticosteroids and androgens. To establish whether chronic therapy with simvastatin interferes with the integrity of the hypothalamic-pituitary-adrenal axis and with the adrenal and testicular reserve, we administered simvastatin orally in a single-day 10 mg dose for 6 months in 8 mildly hypercholesterolemic male patients. At weeks 0, 6 and 24 of treatment we evaluated the lipids, the activity of the hypothalamic-pituitary-adrenal axis by means of the Corticotropin-Releasing Hormone (CRH) test, the adrenal reserve by means of the Corticotropin rapid test and, finally, the testicular reserve by means of the Human Chorionic Gonadotropin (HCG) test. Total cholesterol and LDL-cholesterol were significantly reduced by Simvastatin, while the HDL-cholesterol and triglycerides did not change significantly. The hormonal responses to CRH, ACTH and HCG tests at weeks 6 and 24 of treatment were comparable to those obtained in basal conditions. We conclude that Simvastatin, while effective in reducing total and LDL-cholesterol in hypercholesterolemic male patients, did not interfere with hypothalamic-pituitary-adrenal axis activity or with basal and stimulated adrenal and testicular steroidogenesis.

Does Atorvastatin Affect Androgen Levels in Men in the Era of Very-low LDL Targeting Therapy?

“…Effect of high dose atorvastatin on gonadal steroidogenesis was similar to effect of regular doses. Our results are consistent with prior research on this subject, most of which found no effect of statin treatment on male gonadal function ( Travia et al, 1995 ), ( Dobs et al, 1993 ), ( Azzarito et al, 1992 ), ( Bernini et al, 1994 ), ( Jay et al, 1991 ), ( Purvis et al, 1992 ) however in these prior studies mean post treatment LDL levels are consistently above 100 mg / dl, reaching around 180 mg / dl in one of them. ( Travia et al, 1995 ) These post treatment LDL levels are considered unacceptable in current medical practice, particularly in very high risk patients requiring secondary prevention for coronary heart disease.…”

“…( ATP III fi nal report, 2002 ) So, it may be controversial to consider the data generated by prior studies on this issue as valid in contemporary clinical practice. The main reason for this confounding factor is that the effect of peripheral LDL on steroidogenesis is dose dependent ( Tureck and Strauss, 1982 ) and post treatment LDL levels of prior studies on this issue are quite higher ( Travia et al, 1995 ), ( Dobs et al, 1993 ), ( Azzarito et al, 1992 ), ( Bernini et al, 1994 ), ( Jay et al, 1991 ), ( Purvis et al, 1992 ) than the contemporary guideline recommendations. Another hypothetical factor that may alter effect of different statins on steroidogenesis is the hydrophilic or lipophillic property of the individual statin molecule.…”

The current evidence on statin use and prostate cancer prevention: are we there yet?

“…Some studies have suggested that statins reduce serum testosterone levels 46–48 , but these reductions were small or caused by statin doses that were higher than commonly used in clinical practice. Other observational studies 49,50 and two clinical trials 51,52 found no association between statin use and serum androgen levels. A study in 1,812 men in the Boston Area Community Health Survey cohort of which 237 men were statin users found no association between statin use and serum androgen levels 53 .…”

Testicular Function in Hypercholesterolemic Male Patients During Prolonged Simvastatin Treatment

“…The four existing studies on simvastatin (Purvis et al 1992;Balestrieri et al 1990;Bernini, Argenio, Gasperi, Vivaldi, Franchi and Salvetti 1994; Rossato, Guarneri, Lavagnini, Padovan and Foresta 1993), did not demonstrate any reduction of testo sterone after 3.5, 6 and 12 months of treatment. However, the fourth (Rossato et at.…”