Estradiol, the most important biologically active estrogen, has important functions in men [257]. One of the most critical is its role in bone metabolism.

Men with aromatase deficiency or inactive estrogen receptor a develop severe osteoporosis. Most of the effects of T on bone depend on its aromatization into estradiol. Estradiol is also supposed to be the main active metabolite of T concerning its effects on the brain, though no significant sexual dysfunction was observed in men affected by congenital estrogen deficiency [258-260]. However in two men with aro-matase deficiency, Carani etal. observed a synergistic effect of estradiol and T on sexual behavior

In men about 20% of estradiol is formed in the Leydig cells, and the rest in peripheral tissues, especially fat cells, from aromatization of androgens— mainly T but also adrenal androstenedione [1]. As a result, the estradiol level is higher in men with increased BMI, as well as in diabetic patients, while aromatization seems decreased by physical exercise [257]. According to the studies there is no or only a slight decrease of serum estradiol with age, resulting in an increase in the estradiol/T ratio. However serum levels of free estradiol decrease because concentrations of SHBG, which binds estradiol, increase with age.

Animal experiments from Adaikan and co-workers show that any estrogen increase results in a reduction of circulating T levels (probably due to inhibition of the gonadotropic axis at the hypothalam-ic level, where estradiol is the active metabolite of T for its negative feedback action) and that the resulting estrogen/T imbalance precipitates ED in both rats

[262] and rabbits [263] by reducing intracavenosal pressure response to nerve stimulation, reducing relaxant response to acetylcholine and nitrergic transmission, and potentiating norepinephrine-induced anti-erectile contraction of corpora cavernosa

[263]. Trichrome staining highlighted cavernosal connective tissue hyperplasia in the long-term study groups [262]. These effects were observed following both estradiol and phytoestrogen administrations [263] leading to conjecture about the impact of exposure to environmental estrogens on male sexual function. One study of ED patients reported a high prevalence of exposure to pesticides, some of which have estrogenic or anti-androgenic properties, and an association between such an exposure and the severity of ED based on flat nocturnal erectile pattern was made [264]. Mancini et al. also observed increased estradiol levels in a small group of ED

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