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.
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