Hypogonadism and erectile dysfunction—F
Further evidence for the role of androgens in erectile
dysfunction comes from clinical studies. In the 1980s, Bancroft performed pivotal studies to discriminate central effects from peripheral effects of testosterone replacement therapy. He showed that in acute settings, erectile capacity in response to visual stimulation is less sensitive to androgen than sexual interest, fantasies and cognitive sexual activities70
That is, androgen enhances the sexual response to sexual fantasy more than it enhances the response to visual stimuli, which has implications for the kind of sexual activity measured in the research setting. Experimental endogenous
hypogonadism induced by gonadotropinreleasing hormone (GnRH) agonists71 in supraphysiological-dose studies72 generated the threshold hypothesis, confirmed by
epidemiological data, that at least 8 nmol l−1 of testosterone in sera is required for erectile function.
However, some hypogonadal men retain near-normal sexual activity despite very low testosterone levels. In young adults, the androgen dependency of erectile function is maintained at threshold values that are far below those required to maintain the function of other target organs,
However, erectile function despite low androgen levels may not apply to elderly men who have comorbidities, possibly owing to changes in androgen receptor expression and activity. To match testosterone levels to an individual’s own requirement, the concept of compensated or subclinical hypogonadism74 has been introduced (FIG. 6). In this setting, it is suggested that when testosterone declines from a previously higher level, a rise in the levels of luteinizing hormone might be a biomarker for insufficient androgenization74,75
Other evidence for a role of testosterone in erectile dysfunction comes from clinical trial data on testosterone replacement therapy. The few available
randomized clinical trials addressing the roles of treatment with testosterone in erectile dysfunction have been extensively reviewed, with the largest and most updated meta-analysis confirming significant beneficial effects on various domains of erectile function, but only in men with testosterone levels of less than 12 nmol l−1 (345 ng dl−1) at baseline76.
