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17ß-estradiol 

17ß-estradiol (E2), a major metabolite of testosterone, was found to be slightly elevated as compared to controls while patients were undergoing gonadotropin replacement. About 50-75 % of circulating E2 is derived from extragonadal aromatization of testosterone by fat, bone, brain, testes and other tissues 47. Although we matched for serum T in both cohorts, mean serum T levels were slightly higher during gonadotropin application, compared to the situation during T treatment. This explains why T was aromatized to a greater extent during hCG/rFSH substitution. Alternatively, the higher E2 levels could be interpreted as an enhancement of aromatase activity by hCG/rFSH. E2 acts on estrogen receptors alpha and beta (ERα and ERβ) that are present in reproductive organs, brain, bone, blood vessels, liver, and skin and breast tissue. Many biologic effects, hitherto attributed to testosterone are conveyed by estradiol: estrogen action is important for the regulation of spermatogenesis; E2 is involved in the regulation of the somatotropic axis, it mediates epiphyseal closure in bones, improves bone mineralization and bone microarchitecture, decreases fat mass, thereby favoring lean body mass. In addition, it positively affects glucose metabolism by enhancing insulin sensitivity and conveys vasomotor stability 48-50.