We investigated whether letrozole (2.5 mg day 21 ) improves sperm count in non-obstructive azoospermia (NOA) patients. Four men were included in this study, and they had folliculo-stimulating hormone and other hormone levels within the normal range and no varicoceles or chromosomal aberrations. These four patients were administered letrozole for 3 months. Sperm count, testicular volume, gonadotropin, testosterone (T) and estradiol (E2) blood levels were assessed before, during and 1 week after the suspension of treatment. All patients showed spermatozoa in their ejaculate, increased gonadotropin and T levels and lower E2 levels (P,0.05 in all cases), when letrozole was administered. This suggests that letrozole treatment might improve sperm count in an NOA sub-population; however, more studies, including the proper controls, are needed to confirm its efficacy. Asian Journal of Andrology (2011) 13, 895-897; doi:10.1038/aja.2011.44; published online 27 June 2011Keywords: letrozole; medical treatment; non-obstructive azoospermia; spermatogenesis INTRODUCTION Azoospermia indicates the absence of spermatozoa in the ejaculate after two assessments of centrifuged semen. Its prevalence is about 1% in the general population and 10%-15% in infertile couples. 1 Azoospermia is classified as obstructive (OA) or non-obstructive (NOA). NOA is defined by the clinical evidence of strongly affected spermatogenesis, and OA results from a seminal-tract obstruction. Men with OA typically have normal-sized testes, possible epididymal fullness and normal serum follicle-stimulating hormone (FSH) levels. Men with NOA present frequently with small testes and an elevated FSH level; however, a minority of these men have normal testicles and FSH levels within the normal range. 2 Only men with hypogonadotropic-hypogonadism NOA or varicocele-associated NOA may yield spermatozoa in their ejaculate after treatment; however, the majority of men with NOA and normal or elevated FSH levels are only able to father children after surgical retrieval of the spermatozoa from the testicles, which is performed by testicular sperm extraction (TESE) or with fine-needle aspiration (FNA). TESE and FNA yield spermatozoa in 30%-60% of cases depending on the technique used. 1 Patry et al. 3 recently reported one case of hypospermatogenesis (having FSH levels within the normal range), which was converted to active spermatogenesis after letrozole (Femara; Sanofi-Novartis, Paris, France) use. However, the patient remained azoospermic due to an obstruction in the epididymis that was not adequately assessed when surgery was performed. Saylam et al. 4 recently treated 17 NOA patients who had low (,10) testosterone (T)/estradiol (E2) ratios with letrozole. Four of these men showed spermatozoa in their ejaculate after 6 months of therapy.