Introduction: Testosterone Replacement Therapy (TRT) is the standard treatment for male late-onset hypogonadism. Short-acting and long-acting testosterone are currently available treatments and have been approved by the Food and Drug Administration (FDA). The administration of exogenous testosterone is known to increase sperm production and T levels in men suffering from late-onset hypogonadism. However, limited research compares the efficacy of these two types of TRT. Objective: This study aims to compare the efficacy of short-acting and long-acting testosterone replacement therapy on sperm production and T levels in men suffering from late-onset hypogonadism. Methods: We searched for electronic databases including PubMed, Cochrane Library, EMBASE, Scopus, Web of Science, Allied and Complementary Medicine Database (AMED), and Google using keywords. All studies were evaluated by three independent reviewers who resolved differences by consensus. Results: We identified 21 studies that met our inclusion criteria. After applying the inclusion criteria, only 21 database sources remain for further analysis. Conclusion: Long-acting formulas affect blood more. RCTs show TU boosts libido and testosterone. Male infertility may result from long-acting TU blocking LH and FSH. TRP improves erections by increasing motile sperm and libido. Peanut allergy-related short-acting TRT causes nausea, itching, and injection-site pain.
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