CHANGES IN THE ENDOCRINOLOGIC MILIEU AFTER CLOMIPHENE CITRATE TREATMENT FOR OLIGOZOOSPERMIA - THE CLINICAL-SIGNIFICANCE OF THE ESTRADIOL TESTOSTERONE RATIO AS A PROGNOSTIC VALUE/

We have already reported that the rate of increase in the estradiol/te stosterone ratio (E(2)/T ratio) following human chorionic gonadotropin (hCG) injection has prognostic value in the treatment of oligozoosper mia. It was found that the rate of increase in the E(2)/T ratio was st atistically greater in the therapeutically ineffective cases compared to the therapeutically effective cases. The present study was planned in order to elucidate the relationship between the changes in the endo crinological milieu, especially the change in the E(2)/T ratio, and th e therapeutic efficacy when clomiphene citrate was administered. Thirt y-eight oligozoospermic patients were administered 25 mg of clomiphene citrate daily for 3 months. Sixteen of the 38 (42.1%) cases showed im provement of more than 10 x 10(6)/ml in sperm concentration. The rate of increase in the E(2)/T ratio of the effective cases (0.90 +/- 0.43) during the administration of clomiphene citrate was statistically (P = 0.02) lower than that of the ineffective cases (1.44 +/- 0.80). The rate of increase in the E(2)/T ratio during clomiphene citrate treatme nt showed a statistically positive correlation (r = 0.542) with the ra te of increase following hCG injection performed before clomiphene cit rate treatment. The rate of increase in follicle-stimulating hormone ( FSH) in the ineffective cases (2.16 +/- 1.01) was statistically higher than in the effective cases (1.50 +/- 0.43). The rate of increase in insulin-like growth factor-1 (IGF-1) in the seminal plasma that was se creted by Sertoli cells was statistically higher in the effective case s (1.98 +/- 1.23) than in the ineffective cases (1.19 +/- 0.45). Based on these results, it is surmised that the relatively increased E(2) l evel during clomiphene citrate treatment suppressed Sertoli cell funct ion, and the serum FSH was elevated as a result. We concluded that the rate of increase in the E(2)/T ratio during clomiphene citrate treatm ent has prognostic value, and performing the hCG test before this trea tment may be helpful in predicting the endocrinological milieu after i t. If the rate of increase in the E(2)/T ratio following hCG injection is high, treatment should consist of a combination of clomiphene citr ate and an aromatase inhibitor to decrease the E(2)/T ratio.