OBJECTIVEThis study evaluated the effects of testosterone replacement therapy (TRT) on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS).RESEARCH DESIGN AND METHODSThe efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men with type 2 diabetes and/or MetS in a multicenter, prospective, randomized, double-blind, placebo-controlled study. The primary outcome was mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were measures of body composition, glycemic control, lipids, and sexual function. Efficacy results focused primarily on months 0−6 (phase 1; no changes in medication allowed). Medication changes were allowed in phase 2 (months 6−12).RESULTSTRT reduced HOMA-IR in the overall population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA1c: treatment difference, −0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a (Lpa), body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate.CONCLUSIONSOver a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.

Introduction The role of testosterone supplementation (TS) as a treatment for male sexual dysfunction remains questionable. Aim The aim of this study was to attempt a meta-analysis on the effect of TS on male sexual function and its synergism with the use of phosphodiesterase type 5 inhibitor (PDE5i). Methods An extensive Medline, Embase, and Cochrane search was performed. Main Outcome Measures All randomized controlled trials (RCTs) comparing the effect of TS vs. placebo or the effect of TS as add on to PDE5is on sexual function were included. Data extraction was performed independently by two of the authors (A. M. Isidori and G. Corona), and conflicts resolved by the third investigator (M. Maggi). Results Out of 1,702 retrieved articles, 41 were included in the study. In particular, 29 compared TS vs. placebo, whereas 12 trials evaluated the effect of TS as add on to PDE5is. TS is able to significantly ameliorate erectile function and to improve other aspects of male sexual response in hypogonadal patients. However, the presence of possible publication bias was detected. After applying “trim and fill” method, the positive effect of TS on erectile function and libido components retained significance only in RCTs partially or completely supported by pharmaceutical companies (confidence interval [0.04–0.53] and [0.12; 0.52], respectively). In addition, we also report that TS could be associated with an improvement in PDE5i outcome. These results were not confirmed in placebo-controlled studies. The majority of studies, however, included mixed eugonadal/hypogonadal subjects, thus imparting uncertainty to the statistical analyses. Conclusions TS plays positive effects on male sexual function in hypogonadal subjects. The role of TS is uncertain in men who are not clearly hypogonadal. The apparent difference between industry-supported and independent studies could depend on trial design more than on publication bias. New RCTs exploring the effect of TS in selected cases of PDE5i failure that persistently retain low testosterone levels are advisable.

Erectile dysfunction (ED), generally associated with reduced sexual desire and sometimes with orgasmic or ejaculatory dysfunction, is the major revealing symptom of hyperprolactinemia (HPRL) in men, a condition that should not be neglected since many cases result from pituitary tumors, likely to result in serious complications. It is generally believed that the mechanism of the prolactin (PRL)-induced sexual dysfunctions is a decrease in testosterone secretion. In fact, serum testosterone is normal in many hyperprolactinemic males and there are also testosteroneindependent mechanisms, probably mainly set at the level of the brain's neurotransmittor systems. Systematic determinations of serum PRL found very low prevalences of marked HPRL (435 ng/ml) in ED patients (0.76% in a compilation of over 3200 patients) as well as of pituitary adenomas (0.4%). In addition, the association of HPRL with ED may have been coincidental in some of these cases, since 10% of the HPRLs diagnosed by the usual immunological assays are composed of macroprolactins, which are biologically inactive or little active variants of PRL. Their identification requires a PRL chromatography that is restricted to some specialized laboratories. There is presently no consensus with regards to the screening for HPRL in ED: systematic determination of serum PRL may be justified since HPRL is a serious but reversible disease, while there is presently no reliable clinical, psychometric or hormonal criteria (including serum testosterone level) allowing to restrict its determination to certain categories of the ED patients without risk of neglecting some HPRLs. In case of consistent HPRL, searching for a hypothalamic or pituitary tumor is mandatory. Dopamine-agonist therapy is the first choice treatment for the PRL-induced sexual dysfunctions. Additional sexual counselling may be necessary for certain patients. Keywords: hyperprolactinemia; erectile dysfunction; inhibited sexual desire; anorgasmia; retarded ejaculation; review Prolactin (PRL) has no known role in physiological control of human sexual behavior, except a possible contribution of the orgasm-induced PRL secretion to the sexual-satiation mechanisms, since sexual satiation has not been observed in a multiorgasmic male. 1 On the contrary, all types of hyperprolactinemia (HPRL) (idiopathic, tumoral or drug-induced) can inhibit most aspects of male sexual behavior. Therefore, although HPRL is a rather rare condition, it may be a cause of male sexual dysfunction, and should not be neglected since it is reversible, and may result from pituitary tumors likely to result in serious endocrine and visual complications due to the tumor's growth. Sexual problems of hyperprolactinemic menA literature review encompassing more than 300 hyperprolactinemic men 2 found sexual dysfunctions in 88%, including erectile dysfunction (ED) almost each time. The most typical pattern associated ED with a reduced sexual desire. Delayed or absent orgasm was associated in some cases, but virtually never isolated. Some cases ...

Introduction Besides hypogonadism, other endocrine disorders have been associated with male sexual dysfunction (MSD). Aim To review the role of the pituitary hormone prolactin (PRL), growth hormone (GH), thyroid hormones, and adrenal androgens in MSD. Methods A systematic search of published evidence was performed using Medline (1969 to September 2011). Oxford Centre for Evidence-Based Medicine—Levels of Evidence (March 2009) was applied when possible. Main Outcome Measures The most important evidence regarding the role played by PRL, GH, thyroid, and adrenal hormone was reviewed and discussed. Results Only severe hyperprolactinemia (>35 ng/mL or 735 mU/L), often related to a pituitary tumor, has a negative impact on sexual function, impairing sexual desire, testosterone production, and, through the latter, erectile function due to a dual effect: mass effect and PRL-induced suppression on gonadotropin secretion. The latter is PRL-level dependent. Emerging evidence indicates that hyperthyroidism is associated with an increased risk of premature ejaculation and might also be associated with erectile dysfunction (ED), whereas hypothyroidism mainly affects sexual desire and impairs the ejaculatory reflex. However, the real incidence of thyroid dysfunction in subjects with sexual problems needs to be evaluated. Prevalence of ED and decreased libido increase in acromegalic patients; however, it is still a matter of debate whether GH excess (acromegaly) may create effects due to a direct overproduction of GH/insulin-like growth factor 1 or because of the pituitary mass effects on gonadotropic cells, resulting in hypogonadism. Finally, although dehydroepiandrosterone (DHEA) and its sulfate have been implicated in a broad range of biological derangements, controlled trials have shown that DHEA administration is not useful for improving male sexual function. Conclusions While the association between hyperprolactinemia and hypoactive sexual desire is well defined, more studies are needed to completely understand the role of other hormones in regulating male sexual functioning.

Introduction. The role of testosterone supplementation (TS) as a treatment for male sexual dysfunction remains questionable. The aim of this study was to attempt a meta-analysis on the effect of TS on male sexual function and its synergism with the use of phosphodiesterase type 5 inhibitor (PDE5i). Methods. An extensive Medline, Embase, and Cochrane search was performed. Main Outcome Measures. All randomized controlled trials (RCTs) comparing the effect of TS vs. placebo or the effect of TS as add on to PDE5is on sexual function were included. Data extraction was performed independently by two of the authors (A. M. Isidori and G. Corona), and conflicts resolved by the third investigator (M. Maggi).