Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment

Abstract

Context: 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. Objective: To evaluate the use of clomiphene as a treatment for persistent hypogonadism in males with prolactinomas. Design: Open label, single-arm, prospective trial. Patients: Fourteen adult hypogonadal males (testosterone !300 ng/dl and low/normal LH) with prolactinomas on DA, including seven with high prolactin (range: 29-1255 mg/l; median: 101 mg/l) despite maximal doses of DA. Intervention: Clomiphene (50 mg/day orally) for 12 weeks. Measures: 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. Results: Ten patients (71%), five hyperprolactinemic and two normoprolactinemic, responded to clomiphene (testosterone O300 ng/dl). Testosterone levels increased from 201G22 to 457 G37 ng/dl, 436G52, and 440G47 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 1.7G0.4 to 6.2G2.0 IU/l, 4.5G0.7, and 4.6G0.7 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. Conclusions: 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.

Clomiphene fails to revert hypogonadism in most male patients with conventionally treated nonfunctioning pituitary adenomas

“…This response was similar to the one previously described in male patients with prolactinomas under dopamine agonist treatment (15). Although this patient did not receive radiotherapy, he had been submitted to pituitary surgery twice.…”

“…This finding is in sharp contrast to the high response rate (71%) we have recently observed in male hypogonadal patients with prolactinomas, treated with clomiphene using the same study protocol (15). Clomiphene failure to restore gonadal function in most patients with treated NFPA is likely to reflect a much lower functional reserve of gonadotrophic cells and/or GnRH neurons in these patients, as compared with prolactinoma patients (20).…”

“…Clomiphene has also been shown to revert hypogonadotropic hypogonadism in several conditions, such as falciform anemia, uremia, alcohol and steroid abuse, and in the stimulation of gonadotropin secretion in patients with sulpiride-induced hyperprolactinemia and gonadotropin suppression (10)(11)(12)(13)(14). More recently, we have shown that clomiphene led to the recovery of gonadal function in most male patients with prolactinomas and persistent hypogonadism under dopamine agonist treatment, irrespective of prolactin levels (15). In this study, we evaluated the therapeutic potential of clomiphene in reverting hypogonadism in patients with conventionally treated NFPA.…”

Oral Enclomiphene Citrate Stimulates the Endogenous Production of Testosterone and Sperm Counts in Men with Low Testosterone: Comparison with Testosterone Gel

“…It is often used off‐label in men who have low testosterone and is useful for the restoration of sperm counts in men who have used exogenous testosterone to relieve symptoms of secondary hypogonadotropic hypogonadism. Clomiphene citrate restores normal testosterone levels and improves sperm motility in most male patients with prolactinomas and persistent hypogonadism under dopamine agonist therapy . Clomiphene citrate is a mixture of two diastereoisomers, a cis isomer, zuclomiphene citrate (38%), and a trans isomer, enclomiphene citrate (62% [a.k.a.…”

Clomiphene Stimulation Test in Men Abusing Anabolic-Androgenic Steroids for Long Time

“…The CST in healthy subjects leads to doubling of LH, 20-50% increase of FSH and 30-220% increase of testosterone concentration [12]. A similar situation is observed in men with hyperprolactinemia [28] or during aging [29].…”