Quantitation of Normal and Abnormal Germinal Cells Following Administration of Clomiphene Citrate in Normal Men1

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Abstract
Clomiphene citrate (50–400 mg daily) was administered to 8 normal men for periods of 2–12 months. Control and administration testicular biopsies were obtained. Seminal fluid, observed at weekly intervals, revealed a rise in sperm counts in 3 subjects, a partial fall in 2 and a precipitous fall to azoospermia in 3. In order to analyze the germinal cell alterations responsible for these divergent results, quantitative analysis of the germinal cells found in testicular biopsies was undertaken using the Sertoli cell as a constant. It was found that A dark spermatogonia did not change, while the A pale and B spermatogonia and primary spermatocytes were increased in each of the 8 subjects after clomiphene administration, significant at the p = 0.004 level. Spermatids were generally increased in subjects who had a rise in sperm count and decreased in subjects who had a precipitous fall to azoospermia. No change in the percentage of abnormal cells occurred in subjects who had a rise in sperm count. The percentage of abnormal cells was greatly increased in subjects who had a precipitous fall to azoospermia. In descending order of magnitude the numbers of morphological abnormalities were found in Sc-Sd spermatids, Sa-Sb spermatids, spermatocytes and spermatogonia. The reduction in the numbers of ejaculated spermatozoa is accounted for by resorption of degenerating spermatids in the ductular system and/or by the Sertoli cells. Clomiphene citrate, therefore, evoked 2 actions upon the germinal epithelium: a primary stimulatory action manifested by increased cell numbers and a secondary inhibitory action generally observed at higher doses and reflected by many abnormal spermatids and a fall in ejaculated spermatozoa.

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