Aromatase inhibitors for male infertility.
OBJECTIVE
Testosterone-to-estradiol ratio levels in infertile men improve during treatment with the aromatase inhibitor, testolactone, and resulting changes in semen parameters. We evaluated the effect of anastrozole, a more selective aromatase inhibitor, on the hormonal and semen profiles of infertile men with abnormal baseline testosterone-to-estradiol ratios.


METHODS
A total of 140 subfertile men with abnormal testosterone-to-estradiol ratios were treated with 100 to 200 mg. testolactone daily or 1 mg. anastrozole daily. Changes in testosterone, estradiol, testosterone-to-estradiol ratios and semen parameters were evaluated during therapy. The effect of obesity, diagnosis of the Klinefelter syndrome, and presence of varicocele and/or history of varicocele repair on treatment results was studied.


RESULTS
Men treated with testolactone had an increase in testosterone-to-estradiol ratios during therapy (mean plus or minus standard error of the mean 5.3 +/- 0.2 versus 12.4 +/- 1.1, p <0.001). This change was confirmed in subgroups of men with the Klinefelter syndrome, a history of varicocele repair and those with varicocele. A total of 12 oligospermic men had semen analysis before and during testolactone treatment with an increase in sperm concentration (5.5 versus 11.2 million sperm per ml., p <0.01), motility (14.7% versus 21.0%, p <0.05), morphology (6.5% versus 12.8%, p = 0.05), and motility index (606.3 versus 1685.2 million motile sperm per ejaculate, respectively, p <0.05) appreciated. During anastrozole treatment, similar changes in the testosterone-to-estradiol ratios were seen (7.2 +/- 0.3 versus 18.1 +/- 1.0, respectively, p <0.001). This improvement of hormonal parameters was noted for all subgroups except those patients with the Klinefelter syndrome. A total of 25 oligospermic men with semen analysis before and during anastrozole treatment had an increase in semen volume (2.9 versus 3.5 ml., p <0.05), sperm concentration (5.5 versus 15.6 million sperm per ml., p <0.001) and motility index (832.8 versus 2930.8 million motile sperm per ejaculate, respectively, p <0.005). These changes were similar to those observed in men treated with testolactone. No significant difference in serum testosterone levels during treatment with testolactone and anastrozole was observed. However, the anastrozole treatment group did have a statistically better improvement of serum estradiol concentration and testosterone-to-estradiol ratios (p <0.001).


CONCLUSIONS
Men who are infertile with a low serum testosterone-to-estradiol ratio can be treated with an aromatase inhibitor. With treatment, an increase in testosterone-to-estradiol ratio occurred in association with increased semen parameters. Anastrozole and testolactone have similar effects on hormonal profiles and semen analysis. Anastrazole appears to be at least as effective as testolactone for treating men with abnormal testosterone-to-estradiol ratios, except for the subset with the Klinefelter syndrome, who appeared to be more effectively treated with testolactone.
Raman
Jay D
JD
Department of Urology, James Buchanan Brady Urology Foundation, Center for Male Reproductive Medicine and Microsurgery, New York Presbyterian Hospital, Weill Medical College of Cornell University, New York, New York, USA.
Schlegel
Peter N
PN
D000077384:Anastrozole; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004958:Estradiol / Q000097:blood; D006801:Humans; D007248:Infertility, Male / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007713:Klinefelter Syndrome / Q000150:complications; D008111:Liver Function Tests; D008297:Male; D009570:Nitriles / Q000627:therapeutic use*; D013081:Sperm Motility; D013738:Testolactone / Q000627:therapeutic use*; D013739:Testosterone / Q000097:blood; D014230:Triazoles / Q000627:therapeutic use*
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D013739:Testosterone; D004958:Estradiol; D013738:Testolactone