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


METHODS
Open label, single-arm, prospective trial.


METHODS
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.


METHODS
Clomiphene (50 mg/day orally) for 12 weeks.


METHODS
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 >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.


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.
Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo, 910. São Paulo 04039-002, Brasil.
Rogerio Silicani
RS
Ribeiro
Julio
J
Abucham
D000328:Adult; D001823:Body Composition / Q000187:drug effects; D002996:Clomiphene / Q000008:administration & dosage*; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004734:Energy Metabolism / Q000187:drug effects; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D004965:Estrogen Antagonists / Q000008:administration & dosage*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D015175:Prolactinoma / Q000188:drug therapy* / Q000378:metabolism; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D020127:Recovery of Function / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D055815:Young Adult
D018491:Dopamine Agonists; D004965:Estrogen Antagonists; D002996:Clomiphene; D013739:Testosterone; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D017430:Prostate-Specific Antigen