Do men with normal testosterone-oestradiol ratios benefit from letrozole for the treatment of male infertility?

RESEARCH QUESTION: Previous studies of aromatase inhibitors on male infertility have focused on men with low testosterone-oestradiol ratio of less than 10. Can aromatase inhibitors improve spermatogenesis in men with idiopathic male infertility with normal testosterone-oestradiol ratio?

DESIGN

Prospective study of men with idiopathic severe oligozoospermia (sperm concentration <5 million/ml) carried out between February 2015 and March 2017. The objective was to assess if semen-analysis parameters improved after treatment with letrozole. Secondary objectives were to monitor the safety of letrozole in men, and to measure the alterations in serum FSH, LH, oestradiol and testosterone levels.

RESULTS

Fifteen men with normal testosterone-oestradiol ratio (>10) were treated with letrozole 2.5 mg daily for 4 months. This produced a 5.5-fold increase in sperm concentration (P = 0.0068). All men had increased total serum testosterone and suppressed oestradiol levels after treatment, thus raising the overall testosterone-oestradiol ratio (P < 0.0001). Adverse effects from letrozole were relatively minor and included loss of libido (54%), headaches (25%), fatigue (21%), weakness (13%), loss of hair (8%) and dry mouth (8%).

CONCLUSIONS

Letrozole improves sperm concentration and increases testosterone-oestradiol ratio for men with oligozoospermia who have normal testosterone-oestradiol ratio; its role in the treatment of male infertility may be extended to this group of patients. In addition, it is a relatively well-tolerated drug with no serious adverse effects.