Obesity is an important risk factor for many common diseases including cardiovascular disease (CVD), type 2 diabetes, cancer and erectile dysfunction (ED). Adipose tissues produce a number of adipokines and cytokines, which affect endothelial and metabolic function resulting in insulin resistance and the metabolic syndrome (risks factors for CVD). Both ED and metabolic syndrome improve with a reduction in body mass index (BMI). The relationships among obesity, metabolic syndrome, ED, sex hormonebinding globulin (SHBG) and serum total and free testosterone levels are complex and often confusing to the physician. It is known that BMI is inversely proportional to serum total testosterone concentrations; low serum SHBG levels in obesity contribute to the low serum total testosterone. Recent studies show that BMI is also inversely proportional to free testosterone concentration. The characteristic low serum testosterone concentrations observed in obese men are also present in men with the metabolic syndrome and type 2 diabetes mellitus. A small proportion of men with ED have hypogonadism; however, the proportion increases if these men are obese with manifestations of the metabolic syndrome or type 2 diabetes mellitus. ED is a common symptom in patients with type 2 diabetes who also have low testosterone levels. This review describes the relationships between low serum testosterone concentrations and ED in obese patients and those with metabolic syndrome and type 2 diabetes mellitus.

Understanding the molecular mechanisms of germ cell apoptosis is essential for male contraceptive development and infertility treatment. We have demonstrated that testosterone (T) implant (3 cm) increases germ cell apoptosis exclusively during stages VII-VIII of the seminiferous epithelium cycle. However, the underlying molecular mechanisms of exogenous T-mediated apoptosis remains an interesting and underexplored question. The objective of this study was to examine the role of estrogen receptor beta (ERβ) on exogenous T-induced germ cell apoptosis in rats. Groups of five young adult (60 days old) Sprague-Dawley rats were given either 3 cm T implant or empty Silastic capsule (control) for 4 weeks. Reproductive hormones were assayed by radioimmunoassay. Germ cell apoptosis was detected by TUNEL assay. Western blot and immunohistochemistry were used to examine ERβ expression and localization in the testis. We found that consistent with our previous observations, plasma FSH, LH, and intratesticular T levels were markedly suppressed in the T-treated group when compared to the controls. Suppression of intratesticular T was followed by an increase in germ cell apoptosis exclusively during the androgen-responsive stages VII-VIII. In control rats, ERβ immunostaining was observed in the Leydig cells, preleptotene and pachytene spermatocytes. After T treatment for 4 weeks, ERβ immunoexpression was increased in Leydig cells. Interestingly, we found ERβ immunoexpression was up-regulated in the apoptotic pachytene spermatocytes and round spermatids. In conclusion, the overexpression of ERβ in apoptotic germ cells suggests the involvement of ERβ in the induction of germ cell apoptosis induced by T implantation in rats. Studying ERβ-mediated cell death and survival, pathways may give rise to potential targets for male contraceptive development and infertility intervention.