Platinum Priority – Collaborative Review – AndrologyEditorial by Alvaro Morales on pp. 113–114 of this issueA Critical Analysis of the Role of Testosterone in Erectile Function: From Pathophysiology to Treatment—A Systematic Review
Introduction
Erectile dysfunction (ED) has emerged as an important marker of cardiovascular (CV) and overall health, independently of other known conventional risk factors [1]. Normal sexual activity throughout the adult lifespan has been associated with a reduced incidence of CV events, suggesting a protective role [2]. Coronary artery disease is preceded by ED in half of the affected subjects, underlining the need for proper screening [3]. Sexual dysfunction is the most specific symptom of late-onset hypogonadism (LOH) [4] in the aging man, a condition also associated with an increased mortality for CV events [5]. However, ED still remains largely underdiagnosed and untreated. The Global Study of Sexual Attitudes and Behavior showed that < 30% of men with ED had sought medical help, due to high social and personal barriers [6].
Public awareness of the benefits of phosphodiesterase type 5 inhibitors (PDE5-Is) has significantly shortened the time lag between the onset of ED and the seeking of medical help [7]. The same cannot be said for testosterone replacement therapy (TRT) in LOH, despite the availability of excellent multifaceted treatment options, due to the long-standing controversies surrounding safety versus efficacy in male sexual dysfunction. The scientific community is sharply divided into those for or against TRT, with a proliferation of studies with apparently contradictory findings, generating a debate without comparison in any other hormone deficiency.
These considerations prompted us to perform a critical appraisal of the major studies of TRT in sexual dysfunction, focusing on three of the critical questions: (1) Is TRT worthwhile in ED patients? If so, how and when? (2) Does testosterone (T) act centrally or peripherally? (3) What are the underlying facts and beliefs about the combination of T and PD5-I therapy? Is it safe?
Section snippets
Evidence acquisition
We reviewed the relevant medical literature, with a particular emphasis on original molecular studies, prospective observational data, and randomized controlled trials (RCTs) performed in past 20 yr that included the search terms testosterone or hypogonadism and erectile function (EF). We provide a systematic review and critical appraisal of the data (see Supplement).
Hormonal assessment in erectile dysfunction patients
The European Male Ageing Study (EMAS) found that 30% of European men experienced ED and two-thirds of them were eugonadal [4]. In representative samples, the prevalence of hypogonadism ranges between 23% and 36% of ED subjects [8] and varies according to the cut-off value adopted for the diagnosis, respectively 7%, 23%, 33%, or 47% for T levels of <7, 10.4, 12, or 14 nmol/l [9]. These figures, however, are simple associations that do not imply any causal association between the two conditions.
Conclusions
All subjects with an organic cause of primary or secondary hypogonadism, especially if young and with a significant drop in T levels, should receive TRT as first-line treatment. Restoration of sleeping/morning erections should be monitored and, if necessary, PDE5-I added. In adults with LOH or any psychological distress, comorbidity, or drug-related marginally reduced T level, a PDE5-I should be administered first in the attempt to restore sexual function, medications affecting sexuality should
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