Multivariate analysis to predict letrozole efficacy in improving sperm count of non-obstructive azoospermic and cryptozoospermic patients: a pilot study.

We tested the hypothesis that letrozole increases sperm count in non-obstructive azoospermic or cryptozoospermic patients with a testosterone (T)/17-beta-2-oestradiol (E2) ratio <10. Forty-six patients with no chromosomal aberrations were randomized into two groups: 22 received letrozole 2.5 mg per day for 6 months (Group 1: 6 azoospermic + 16 cryptozoospermic patients), while 24 received a placebo (Group 2: 5 azoospermic + 19 cryptozoospermic patients). The following data were collected: two semen analyses, clinical history, scrotal Duplex scans, body mass index (BMI), Y microdeletion, karyotype and cystic fibrosis screens and follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, T and prolactin levels. Both before and after letrozole or placebo administration, the patients underwent two semen analyses and hormonal assessments. The differences were evaluated using the Mann-Whitney U test. The relationships between sperm concentration after letrozole administration with respect to FSH, T/E2 ratio, bilateral testicle volume and BMI before letrozole administration were assessed using multivariate analysis. The side effects were assessed using the chi-square test. Group 1 had sperm concentration (medians: 400-1.290 × 10(6) ml(-1); P<0.01) and motility (medians: class A from 2% to 15%; P<0.01), FSH, LH and T significantly increased, while Group 2 did not. E2 levels diminished significantly in Group 1, but not in Group 2. Eight patients in Group 1 demonstrated side effects, whereas no patient side effects were observed in Group 2. The sperm concentration after letrozole administration is inversely related to T/E2, FSH and BMI; a direct relationship emerged between sperm concentration and testicular volume.