Aim: To study the anti-spermatogenic mechanism of supra-physiological doses of testosterone undecanoate (TU). Methods: Twenty fertile adult men received four intramuscular injections of TU at monthly intervals, 1000 mg upon admission and 500 mg for the subsequent injections. The apoptotic germ cells in the semen were studied under light microscope with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Wright-Giemsa staining methods. Results: After treatment, the sperm density and the number of spermatogenic cells in the semen were significantly decreased (P<0.01), while the apoptotic ratios of spermatocytes and spermatids increased significantly (P<0.01) as compared with the pretreatment levels. Apoptosis was found to be augmented in the whole series of castoff spermatogenic cells. Conclusion: Besides its suppressive effect on spermatogenesis through a negative feed-back mechanism, TU enhances apoptosis of spermatogenic cells, which may be an additional mechanism of its anti-spermatogenic activity.

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