Controversial aspects of testosterone in the regulation of sexual function in late‐onset hypogonadism

Abstract

Background Testosterone (T) plays a pivotal role in coordinating a series of psychological, cognitive and physical events that might (or might not) culminate in male sexual activity. In fact, T deficiency is associated, in a statistically significant way, with several sexual dysfunctions including erectile dysfunction (ED), reduction of spontaneous erection and hypoactive sexual desire (HSD). Although these associations are statistically significant, there is debate if they are also clinically meaningful. In addition, sexual dysfunctions are present also in several metabolic conditions ‐ such as type 2 diabetes mellitus and obesity ‐ that often associate with low T. In particular, this is the case of ED, but not of HSD, that, therefore, should be considered a more genuine correlate of T deficiency in adulthood and aging (late‐onset hypogonadism, LOH). Objectives The aim of this review is to scrutinize evidence from our and other studies on sexual effects of T replacement therapy (TRT) in LOH. Materials and methods We will use preclinical and clinical data coming from our and other laboratories and meta‐analyses. Results Intervention studies in clinical trials involving subjects with LOH, and their meta‐analyses, indicate that TRT is able to ameliorate HSD, spontaneous erection and ED. However, the relative improvement of ED by TRT is marginal [2‐3 points of International Index of Erectile Function‐erectile function domain (IIEF‐EFD)] and significantly smoothed in subjects with the aforementioned metabolic conditions. In LOH, positive effects of TRT on other domains of sexual activity, such as orgasm and sexual satisfaction, are also apparent in the different meta‐analyses. Discussion and conclusions Hence, TRT is a reasonable treatment for restoring sexual drive in LOH, with some additional positive effects also on erection (spontaneous and sexual‐related) and on orgasm. In contrast, preclinical and clinical studies indicate that T administration to eugonadal subjects does not improve male sexual activity.

Late‐onset hypogonadism a challenging task for the andrology field

“…5 Specific papers included in this special issue analyzed all evidence-based data supporting the role of TRT on several outcomes. [5][6][7][8][9][10] In addition, available on-label and off-label TRT options have been specifically addressed and critically discussed. 11,12 Current evidence supports the role of TRT in improving sexual function in patients with a milder form of ED, whereas the effect of TRT in more complicated ED patients is less effective.…”

“…11,12 Current evidence supports the role of TRT in improving sexual function in patients with a milder form of ED, whereas the effect of TRT in more complicated ED patients is less effective. 6 Conversely, the role of TRT in improving other LOH-related symptoms such as mobility and cognition impairment, as well as mood disturbances, is more conflicting. 7,8 Similarly, despite the fact that reduced T levels have been associated with worse metabolic profiles as well as with a higher cardiovascular (CV) risk, the current data only partially support the use of TRT for improving the latter conditions.…”

“…Specific papers included in this special issue analyzed all evidence‐based data supporting the role of TRT on several outcomes 5‐10 . In addition, available on‐label and off‐label TRT options have been specifically addressed and critically discussed 11,12 .…”

“…In addition, available on‐label and off‐label TRT options have been specifically addressed and critically discussed 11,12 . Current evidence supports the role of TRT in improving sexual function in patients with a milder form of ED, whereas the effect of TRT in more complicated ED patients is less effective 6 . Conversely, the role of TRT in improving other LOH‐related symptoms such as mobility and cognition impairment, as well as mood disturbances, is more conflicting 7,8 .…”

Cardiovascular Risks of Androgen Deprivation Therapy for Prostate Cancer

“…Untreated rabbit were used as a control. Results are derived from data from previous studies[23][24][25][26] and from unpublished observations. RD: regular diet, VAT: visceral adipose tissue.…”