Hormonal Regulation of Spermatogenesis: Why Cellular Context Matters

This critical narrative review assesses how cellular and developmental context shapes hormonal support of spermatogenesis and the translation of experimental findings to human reproductive outcomes. Non-exhaustive PubMed searches were supplemented by citation tracking, trial-registry searches, and targeted source checks. Mouse loss-and-rescue experiments establish Sertoli androgen signaling as a requirement for defined meiotic and postmeiotic functions. Follicle-stimulating hormone supports Sertoli proliferation and metabolism, while intrinsic germ-cell programs impose additional developmental requirements. Reconstructed rodent systems have produced offspring through assisted reproduction; human systems reviewed have not demonstrated equivalent functional gamete production. The proposed cell-state framework separates causal mechanisms, differences in treatment benefit, and outcome prediction. Gonadotropin replacement has its clearest basis in documented hypogonadotropic hypogonadism. In the reviewed evidence, semen or retrieval responses outside deficiency do not establish pregnancy or live-birth benefit. Hormonal contraception demonstrates pregnancy prevention, with regimen-specific safety and recovery constraints.