Testicular responsiveness to hCG before and after long-term antiestrogen treatment in oligozoospermic men.

In order to further investigate the role of endogenous estradiol in the regulation of testicular steroidogenesis an hCG-stimulation test (a single dose of 5000 i.u. i.m.) was performed in 5 normogonadotropic oligozoospermic men before and after 3 months of antiestrogen (clomiphene citrate = CC) treatment (50 mg p.o. daily). Peripheral blood samples were collected immediately before hCG administration and thereafter at 1, 4 and 7 days, and were analyzed for testosterone (T), estradiol (E2), 17-hydroxyprogesterone (17-OHP4), 17-hydroxypregnenolone (17-OHP5), 11 other free and sulfate-conjugated steroids, and for sex hormone-binding globulin (SHBG). The results demonstrated that CC-treatment caused a significant rise in peripheral serum concentrations of SHBG, T, 5 alpha-dihydrotestosterone (DHT), E2 and the sulfate conjugates of pregnenolone, 17-OHP5, 5-androstene-3 beta, 17 beta-diol and T. In the basal state, before the CC-treatment, apparently normal responses to hCG were seen in unconjugated steroids: 17-OHP4 and E2 concentrations were significantly elevated at 1 day, and those of T at 4 days. After CC, only the concentrations of 17-OHP4 rose significantly following hCG administration. The peripheral serum concentrations of the 5-ene- and sulfate-conjugated precursors of T were not influenced by hCG in the basal state or after CC. These results suggest that the apparently E2-mediated inhibition of 17,20-lyase activity in the 4-ene-pathway of T synthesis could not be totally prevented by long-term antiestrogen treatment, and that in the 5-ene-pathway no sign of 17,20-lyase inhibition was demonstrated either before or following CC-treatment. The significant rise in the circulating concentrations of sulfate-conjugated steroids following long-term CC administration, apparently due to increased synthesis of T and its precursors in the 5-ene-pathway, strengthens the concept of their importance in testicular steroidogenesis.