Hormonal therapy for non-obstructive azoospermia: basic and clinical perspectives

Microdissection testicular sperm extraction (micro-TESE) combined with intracytoplasmic sperm injection is a standard therapeutic option for patients with non-obstructive azoospermia (NOA). Hormonal treatment has been believed to be ineffective for NOA because of high gonadotropin levels; however, several studies have stimulated spermatogenesis before or after micro-TESE by using anti-estrogens, aromatase inhibitors, and gonadotropins. These results remain controversial; however, it is obvious that some of the patients showed a distinct improvement in sperm retrieval by micro-TESE, and sperm was observed in the ejaculates of a small number of NOA patients. One potential way to improve spermatogenesis is by optimizing the intratesticular testosterone (ITT) levels. ITT has been shown to be increased after hCG-based hormonal therapy. The androgen receptor that is located on Sertoli cells plays a major role in spermatogenesis, and other hormonal and non-hormonal factors may also be involved. Before establishing a new hormonal treatment protocol to stimulate spermatogenesis in NOA patients, further basic investigations regarding the pathophysiology of spermatogenic impairment are needed. Gaining a better understanding of this issue will allow us to tailor a specific treatment for each patient.