The effects of clomiphene citrate on the normal human male reproductive system.

The reported results of clomiphene citrate (Clomid) administration on the male reproductive system have been inconclusive. We felt that the duration of the observation period was a major factor in the discrepancies reported. We studied Clomid in males for periods of 2-22 months (median 7 months). The following parameters were studies: urinary total gonadotripins. ICSH estrogens and testosterone; seminal fluid and testicular biopsies. Clomid was administered to 11 subjects twice daily at 3 dosage levels; low (50mg/day) intermediate (100 and 200mg/day) and high (400mg/day). The following urinary hormones were significantly increased: total gonadtropins 80-400%; ICSH 160-1200% estrogen 150-680% and 150-680% AND testosterone 140-250%. In each individual the increase in ICSH was greater than the increase in total gonadotropins in the same subject. No dose relationship was observed in any of these hormones. Sperm counts were dose related; low dosages caused an increase; intermediate doses caused an increase decrease or no change and high doses caused preciptous decrases. We conclude that there are 2 direct sites of Clomid action; the hypothalamo- pituitary axis and the spermatids of the germinal epithelium. The stimulation of the brain centers causes an increase in gonadotropins which stimulates both leydig cells and spermatogenesis. At appropriate high doses Clomid interferes with the maturation of spermatids causing a drop in sperm count.(FULL TEXT)