Statin Therapy Is Associated With Lower Total but Not Bioavailable or Free Testosterone in Men With Type 2 Diabetes

Abstract

OBJECTIVE -There is a high prevalence of hypogonadism in men with type 2 diabetes. This will lead to an increase in assessments of hypogonadism. Statins could potentially decrease testosterone levels by reducing the availability of cholesterol for androgen synthesis. We compared testosterone levels and hypogonadal symptoms with statin use in a cross-sectional study of 355 men with type 2 diabetes.RESEARCH DESIGN AND METHODS -Total testosterone, sex hormone-binding globulin (SHBG), and estradiol were measured by an enzyme-linked immunosorbent assay. Bioavailable testosterone was measured by the modified ammonium sulfate precipitation method. Free testosterone was calculated using Vermeulen's formula. Symptoms of hypogonadism were assessed using the Androgen Deficiency in the Aging Male questionnaire.RESULTS -Statins were associated with lower total testosterone (11.9 vs. 13.4 nmol/l, P ϭ 0.006) and a trend toward lower SHBG (29.4 vs. 35.3 nmol/l, P ϭ 0.034) compared with no treatment. Bioavailable testosterone, free testosterone, estradiol, and hypogonadal symptoms were not affected. Subanalysis showed that atorvastatin was associated with reduced total testosterone (11.4 vs. 13.4 nmol/l, P ϭ 0.006) and a trend toward reduced SHBG (27.6 vs. 35.3 nmol/l, P ϭ 0.022) compared with no treatment, and there was an apparent dose-response effect with the lowest levels of total testosterone seen in men treated with Ն20 mg atorvastatin (9.6 nmol/l, P ϭ 0.017). Simvastatin use was not associated with significant reductions in testosterone or SHBG levels.CONCLUSIONS -Assessing androgen status using total testosterone in men with type 2 diabetes treated with statins, particularly atorvastatin, may potentially lead to diagnostic error. Levels of bioavailable testosterone or free testosterone are recommended for the assessment of hypogonadism in this group if total testosterone levels are borderline. Diabetes Care 32:541-546, 2009

Hypogonadism in men with erectile dysfunction may be related to a host of chronic illnesses

“…The incidence in diabetes, 34%, was similar to other reports in the literature. The incidence of hypogonadism seen in other chronic illnesses was substantial: 30.8% in hypertension, 35.0% in atherosclerotic cardiovascular disease, 45.2% in asthma, 34.0% in seizure disorders, 64.3% in sleep apnea, 27.1% in excess alcohol consumption, 37.0% in medicated anxiety/depressive disorders, and 43.6% in work-related job stress. The incidences varied between 27.1 and 64.3%.…”

“…This does prove that there is some overlap and also strongly suggests that psychological stress can indeed lower the testosterone levels. One recent paper called into question the prevalence of hypogonadism in the various medical cofactors 35 in men who take atorvastatin for hyperlipidemia and have lower total testosterone levels than men who took simvastatin or no statin at all. Free and bioavailable testosterone levels were not affected.…”

“…In general, 30-40% of men with diabetes are expected to have lower testosterone levels, the relationship being so strong as to even predict the onset of diabetes. A prevalence of hypogonadism between 33 and 58% has been shown recently in younger diabetic men (ages [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35], when age-related reference ranges for testosterone were used. 13 Although diabetes is the most reported condition related to a high incidence of hypogonadism, many chronic illnesses are reported to be accompanied by a substantial incidence of low testosterone levels.…”

Metabolic syndrome and the effect of testosterone treatment in young men with congenital hypogonadotropic hypogonadism

“…Obesity also increases glucocorticoid turnover (19), which disturbs the regulation of the hypothalamic-pituitary-adrenal axis (44) and contributes to hypoandrogenism. Also, in most of these reports, the study populations were using chronic medications with the potentials to affect the serum testosterone levels (20)(21)(22). In this regard, the data from patients with CHH are of utmost importance, as they may reflect the unconfounded effects of low testosterone levels on metabolic profiles.…”

“…However, the majority of the data showing the association between MS and hypogonadism originate from the obese or elderly population with chronic metabolic disorders (8)(9)(10)(11)(12)(13)(14)(15). Aging, obesity, chronic disorders and several medications commonly used in daily practice can decrease serum testosterone levels (16)(17)(18)(19)(20)(21)(22) and confound the association between hypogonadism and MS. Thus, the unconfounded data of the patients with congenital hypogonadal hypogonadism (CHH) are of utmost importance, as they can provide information about the effects of low testosterone levels on metabolic profiles.…”