Baseline FSH Predicts Semen Parameter Response in Infertile Men on Clomiphene Citrate

Background: Clomiphene citrate (CC) is a selective estrogen receptor modulator that increases gonadotropin production and may improve spermatogenesis. The purpose of the study was to examine the effects of CC on hormone levels and spermatogenesis in men treated for infertility, and to determine whether it is possible to predict positive treatment outcomes, in terms of hormonal or spermatogenic response to CC prior to treatment. Methods: The cases of 90 men, who were prescribed CC for infertility, were retrospectively reviewed. Serum values for follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), free testosterone (FT), sex hormone binding globulin (SHBG), estradiol (E) as well as complete semen analyses were collected before and after CC. Exclusion criteria included azoospermia and men treated with testosterone, human chorionic gonadotropin, or recombinant FSH during the previous 6 months. Results: Forty-two men (46.7%) with a mean age of 35 +/- 6years met the inclusion criteria for analysis. Serum hormone values significantly (p<0.01) increased for FSH (Delta 3.4 mIU/mL), LH (Delta 2.7 mIU/mL), TT (Delta 250.0 ng/dL), FT (Delta 5.2 ng/dL), SHBG (Delta 5.2nmoI/L) and E (Delta 1.9 ng/dL). Patients with a baseline FSH of <= 2 mIU/mL had no change in sperm density (Delta-13.1 +/- 32.0 million/mL) or total motile count (Delta-20.6 +/- 45.5 million). Men with an initial FSH> 2 (n= 32) had a mean change in density of + 1.68 +/- 7.46 million/mL and demonstrateda significant improvement in total motile sperm (Delta+3.4 +/- 13.96 million). There were no significant differences between the serum hormone levels in men with baseline FSH levels of <= 2 or >2 mIU/mL. Conclusions: Infertile men exhibit significant increases in serum hormone levels with CC. Those with FSH >2 mIU/mL had improved sperm density and motility relative to men with FSH <= 2mIU/mL. FSH prior to initiating CC therapy may be a useful predictor of improvement in semen parameters.