Prolactinomas are the most common functional adenomas of the anterior pituitary (representing 60% of hormone-secreting pituitary tumors). Men with prolactinomas usually present with macroadenomas (tumors >10 mm in diameter) and with high prolactin (PRL) levels, erectile dysfunction, loss of libido and/or infertility. These symptoms are related to the hypogonadism that occurs secondary to hyperprolactine-mia (3).
PRL affects the testis directly. PRL receptors are present in all stages of the cycle of the seminiferous epithelium, the surface of Sertoli and Leydig cells, and all phases of spermatogonia and spermatocytes in male rats (4). PRL modulates testosterone production by regulating precursor steroid levels for bioconversion under LH influence. These findings imply that PRL plays a role in the process of spermatogenesis, and normal serum PRL levels are required for normal testicular function.
Clinical Manifestations Secondary to Hypogonadism in Men With Prolactinoma
High levels of PRL suppress GnRH secretion and, consequently, decrease gonadotropin and testosterone production (5,6). In some cases, hyperprolactinemia induces clinical hypogonadism notwithstanding normal serum FSH, LH, and testosterone levels. There is an exaggerated diurnal variation in testosterone in men with PRL-producing tumors, so that normal morning values do not guarantee normal values throughout the day (7). Others have suggested a reduced conversion of testosterone to dihydrotestosterone (DHT) (8,9). If so, the hypogonadism associated with hyperpro-lactinemia may not solely result from the decrease in serum testosterone. In fact, testosterone replacement therapy may not reverse the loss of libido that is typical of men with prolactinoma until the PRL level is normalized by the administration of a dopamine agonist (10). Furthermore, human chorionic gonadotropin (hCG) administration did not increase DHT levels in men with hyperprolactinemia induced by sulpiride treatment, although testosterone levels were significantly increased (11). Another mechanism to explain the suppression of gonadal function in men with prolactinoma is a direct tumor mass effect on gonadotrophs. Large adenomas often cause deficiency of anterior pituitary hormones, including the gonadotropins. However, a tumor mass effect is less important than hyperprolactinemia in the development of hypogonadism in prolactinomas. In fact, there is no significant difference in the prevalence of testosterone deficiency between microprolactinomas and macroprolactinomas, either before or after medical treatment (12). Therefore, hyperprolactinemia produces sexual dysfunction and affects seminal fluid through several mechanisms, causing spermiogenic arrest and impairing sperm motility and/or quality. The development of a mouse line knockout for the PRL receptor could be used to better evaluate the multiple functions of PRL and the effects on testicular function (13).
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