Microphallus: eventual phallic size is dependent on the timing of androgen administration

Micropenis secondary to hypogonadotropic hypogonadism in the Sprague-Dawley rat was induced by either injection of supraphysiological doses of dihydrotestosterone to the timed pregnant dam on gestational days 16 and 17 or by long acting microspheres of the gonadotropic agonist, leuprolide acetate. Following the induction of micropenis the animals were treated with dihydrotestosterone beginning at either day 7, 28, 56 or 84 of life. Within the study populations all animals treated with dihydrotestosterone had phallic enlargement greater than untreated controls (p < 0.01). However, animals beginning treatment on day 7 or 28 had persistent microphallus (p < 0.01). In contrast, if hormonal therapy was initiated on day 56 or 84 the phallus became normal in length. Immunohistological studies for androgen receptor expression revealed that early androgen exposure accelerated the loss of androgen receptor protein from the penis during growth. These data suggest that prepubertal exposure of the penis to androgens may significantly reduce the eventual penile size of the hypogonadotropic hypogonadal micropenis.