The role of aromatization in men

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Data concerning the role of aromatization in the human male are not abundant, but a few studies have determined the consequences of inhibition of aromatase. In one of them, six young (20-26 years) university students were treated with testo-lactone for 6 weeks in a dose that reduced plasma estradiol concentrations to less than 50% of pretreatment concentration. No effect on any indicator of sexual activity, like number of sexual acts, frequency of sexual thoughts or frequency of sexual excitement, was found (Gooren, 1985). These data suggest that aromatization is not a requisite for androgen actions on human male sexual behavior. This idea receives support from results obtained in other groups included in the same study. One group of 12 men was given the estrogen receptor antagonist tamoxifen for 12 weeks. Sexual activity was not affected. Another group of six 'agonadal' (probably meaning castrated) men, that were maintained on a treatment with testosterone undecanoate, a long-acting testosterone ester, were given dihydrotestosterone instead of testosterone undecanoate for a period of 9 weeks. In this group, blood concentrations of testosterone and estradiol were below detection limits already after 4 weeks of treatment, and remained so at 9 weeks. Nevertheless, the men in this group did not report any reduction in sexual behaviors.

The lack of effect of an estrogen antagonist as well as of an aromatase inhibitor in the Gooren (1985) study clearly suggests that estrogen receptors are not involved in the control of sexual behaviors in men. Likewise, the fact that dihydrotestosterone maintained sexual behaviors just as well as testosterone in the 'agonadal' group, despite the fact that no estradiol could be detected in the blood of these men, is additional strong evidence against a role for estrogen receptors. The ineffectiveness of aromatase inhibition has been confirmed in later studies. In one (Bagatell et al., 1994), healthy men between 20 and 40 years of age were treated with a GnRH antagonist for 6 weeks. Ten men received daily injections of testosterone enanthate during this period, while 10 others received testosterone enanthate + the aromatase inhibitor testolactone. The 10 men given only the GnRH antagonist had a dramatic reduction in blood testosterone concentration during the treatment period and sexual behaviors were much reduced from week 4 of treatment and on. The frequency of intercourse, of spontaneous erection, of sexual desire and of sexual fantasies was diminished. After 6 weeks, the frequency of masturbation was also reduced. All these behaviors were unchanged in the group given the aromatase inhibitor in addition to testosterone, in spite of a 75% reduction of blood estradiol concentrations. Similarly, the men given testosterone enanthate without the aromatase inhibitor did not show any change of behavior. This elegant study not only shows that human male sexual behaviors are dependent on adequate blood androgen concentrations, but also that aromatization is of slight, if any, importance. A similar conclusion had already been proposed in a study of androgen supplementation in patients with primary testicular failure, complemented with a group of eugonadal medical students receiving testolactone (Gooren, 1987).

Although the total number of men having participated in the studies outlined in the preceding paragraphs is rather small, the consistent results inspire some confidence. It does not seem too adventurous to propose that aromatization, and hence estrogen receptors, are not of any crucial importance for human male sexual behavior. In that way, humans may be different from rats and some strains of mice. At the same time, there is a curious report describing a man who had been castrated bilaterally because of severe post-vasectomy orchialgia. He maintained an adequate sexual functioning with a combined treatment of estrogens + progesterone. In fact, this regimen seemed more effective than treatment with testosterone enanthate (Davidson et al., 1983). The significance of this single individual should not be overestimated, but some additional data suggest that estradiol may contribute to the maintenance of sexual functioning in men who have been castrated because of prostate cancer (Ellis and Grayhack, 1963; Bergman et al., 1984). However, although the sexual activity of the men treated with estrogens was above that of untreated castrated men, it was far lower than that found in intact men. Thus, estrogens do not seem to be particularly efficient for the maintenance of sexual behavior. In addition, prostate cancer patients have frequently reduced sexual activity for various reasons and do not represent an ideal group for evaluating hypotheses concerning the role of gonadal hormones for sexual behaviors. Nevertheless, despite all their limitations and weaknesses, the studies just mentioned suggest that it might be premature to discard completely the possibility that estrogens somehow influence human male sexual behaviors. At present, though, this possibility lacks convincing empirical support and appears rather remote.

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