Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment.
Persistence of hypogonadism is common in male patients with prolactinomas under dopamine agonist (DA) treatment. Conventional therapy with testosterone causes undesirable fluctuations in serum testosterone levels and inhibition of spermatogenesis. To evaluate the use of clomiphene as a treatment for persistent hypogonadism in males with prolactinomas. Open label, single-arm, prospective trial. Fourteen adult hypogonadal males (testosterone <300 ng/dl and low/normal LH) with prolactinomas on DA, including seven with high prolactin (range: 29-1255 microg/l; median: 101 microg/l) despite maximal doses of DA. Clomiphene (50 mg/day orally) for 12 weeks. Testosterone, estradiol, LH, FSH, and prolactin were measured before and 10 days, 4, 8, and 12 weeks after clomiphene. Erectile function, sperm analysis, body composition, and metabolic profiles were evaluated before and after clomiphene. Ten patients (71%), five hyperprolactinemic and two normoprolactinemic, responded to clomiphene (testosterone >300 ng/dl). Testosterone levels increased from 201+/-22 to 457+/-37 ng/dl, 436+/-52, and 440+/-47 ng/dl at 4, 8, and 12 weeks respectively (0.001<P<0.01). Estradiol increased significantly and peaked at 12 weeks. LH increased from 1.7+/-0.4 to 6.2+/-2.0 IU/l, 4.5+/-0.7, and 4.6+/-0.7 IU/l at 4, 8, and 12 weeks respectively (0.001<P<0.05). FSH levels increased in a similar fashion. Prolactin levels remained unchanged. Erectile function improved (P<0.05) and sperm motility increased (P<0.05) in all six patients with asthenospermia before clomiphene. Clomiphene restores normal testosterone levels and improves sperm motility in most male patients with prolactinomas and persistent hypogonadism under DA therapy. Recovery of gonadal function by clomiphene is independent of prolactin levels.