Nonbacterial pyospermia: a consequence of clomiphene citrate therapy

Since the development of nonbacterial pyospermia in previously nonpyospermic men treated with clomiphene citrate (CC) has been observed, and nonbacterial prostatitis has been after antiestrogen treatment in an animal model, we sought characterize the occurrence of nonbacterial pyospermia in men treated with CC.

Forty-two nonpyospermic men with low serum testosterone levels treated with 25 mg CC/day were retrospectively compared to 27 untreated nonpyospermic men referred for infertility evaluation.

Spontaneous nonbacterial pyospermia developed in CC-treated men [14.3%] at rate nearly twice that observed in controls [7.4%]. Serum testosterone increased in CC-treated men, both pyospermic and nonpyospermic. However, only CC-treated, nonpyospermic men demonstrated improvement in semen characteristics. CC-treated men who developed pyospermia were older than nonpyospermic men [pyospermic, 41.7 +/- 8.1 years; nonpyospermic, 35.6 +/- 4.9 years-P < .01). Men over 35 years of age were over six times as likely to develop pyospermia as men under 35 years of age (P < .05). Eight nonpyospermic, CC-treated men (8/36, 22.2%) have contributed to pregnancies leading to live births, whereas no pyospermic man has done so.

These findings support an association between a nonbacterial inflammatory response of the human male reproductive tract and CC treatment. This pyospermia may occur without significant deterioration of semen characteristics and with an appropriate response to treatment in terms of serum testosterone level. Men over the age of 35 are statistically more likely to develop pyospermia with this therapy. Our results suggest that clomiphene citrate-associated pyospermia has a negative effect on male fertility.