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

Abstract

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.

Predictive factors of successful sperm retrieval on microdissection testicular sperm extraction in Japanese men

“…However, the sperm retrieval rate by micro-TESE, ranging between 20 and 60 % [1][2][3][4], remains unsatisfactory considering the negative physical, emotional, and financial effects of this procedure. Although a new attempt that could improve the chance of successful retrieval by micro-TESE such as hormonal therapy for NOA [12] is desirable, there is no generally accepted method that could drastically improve the success rate of micro-TESE at this moment. Therefore, there is also a pressing need for a reliable marker that will help guide physicians to determine cases for which micro-TESE would be suitable.…”

The development of surgical sperm extraction and new challenges to improve the outcome

“…Hormonal treatments for NOA are considered to be ineffective because of high gonadotropin levels; however, previous studies reported that anti-estrogens, aromatase inhibitors, and gonadotropins stimulated spermatogenesis [81]. Ramasamy et al administered a pretreatment with aromatase inhibitors for patients with Klinefelter's syndrome whose serum testosterone levels were less than 300 ng/dl prior to micro-TESE.…”

“…The administration of gonadotropins to men with NOA is a more comprehensive therapy typically used in combination with hCG and recombinant FSH [81]. Shiraishi et al reviewed 48 men with NOA who had negative sperm retrieval results by micro-TESE.…”

Gonadotoropin actions on spermatogenesis and hormonal therapies for spermatogenic disorders [Review]

“…The pathophysiology of NOA is heterogeneous and some, but not all, patients respond to hormonal therapy including anti-estrogens, aromatase inhibitors and gonadotropins. Such immature germ cells can potentially be further developed as represented by late MA or hypospermatogenesis histology [3]. is secreted rhythmically under the regulation of GnRH and the central nervous system.…”