Evidence of a treatable endocrinopathy in infertile men

Purpose: We establish whether a subset of infertile men have decreased seru m testosterone-to-estradiol ratios and whether this condition can be correc ted with an oral aromatase inhibitor. Materials and Methods: The serum testosterone-to-estradiol ratios of 63 men with severe male factor infertility or hypergonadotropic hypogonadism (mea n follicle-stimulating hormone 21.2 +/- 1.8) were compared with those of an age matched, fertile, control reference group. Of the 63 men 43 were azoos permic with biopsy proved severe male infertility and 20 were oligospermic. The men with the lowest ratios (less than 20th percentile) were treated wi th 50 to 100 mg. of the aromatase inhibitor testolactone orally twice daily . Testosterone-to-estradiol ratios and semen analyses were evaluated during testolactone therapy. Results: Men with severe male infertility had significantly lower testoster one (328 versus 543 ng./dl., p <0.01) and higher estradiol (58.4 versus 43. 5 ng./l., p = 0.01) than fertile control reference subjects, resulting in a decreased testosterone-to-estradiol ratio (x10(-1) = 6.9 +/- 0.6 versus 14 .5 +/- 1.2, respectively, p <0.01). Of the 45 men treated with testolactone a correction of these abnormalities was seen and ratios (x10-1) increased into the normal range (5.0 +/- 0.3 to 12.7 +/- 1.2, p <0.01). Semen analyse s were considered evaluable only in men with sperm in the ejaculate before aromatase inhibitor treatment. Semen analyses before and during testolacton e treatment revealed significant increases in sperm concentration (16.1 to 28.9 million sperm per ml., p = 0.03) and motility (27.1% to 45.3%, p <0.01 ) in 12 oligospermic men. Conclusions: We identified an endocrinopathy in men with severe male factor infertility that is characterized by a decreased serum testosterone-to-est radiol ratio. This ratio can be corrected by aromatase inhibition, resultin g in a significant improvement in semen parameters in oligospermic patients .