Academic Journal
From tablets to targeted therapy: the APHRODITE era in male infertility.
| Τίτλος: | From tablets to targeted therapy: the APHRODITE era in male infertility. |
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| Συγγραφείς: | Esteves SC; ANDROFERT, Andrology and Human Reproduction Clinic, Campinas, Brazil.; Department of Surgery (Division of Urology), University of Campinas (UNICAMP), Campinas, Brazil.; Faculty of Health, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Humaidan P; Faculty of Health, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Skive Regional Hospital, Fertility Unit, Skive, Denmark. |
| Πηγή: | Human reproduction (Oxford, England) [Hum Reprod] 2026 Jun 01; Vol. 41 (6), pp. 847-853. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8701199 Publication Model: Print Cited Medium: Internet ISSN: 1460-2350 (Electronic) Linking ISSN: 02681161 NLM ISO Abbreviation: Hum Reprod Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford, UK : Oxford University Press Original Publication: Oxford ; Washington, DC : Published for the European Society of Human Reproduction and Embryology by IRL Press, [c1986- |
| Ιατρικοί όροι (MeSH): | Infertility, Male*/drug therapy, Aromatase Inhibitors/therapeutic use ; Clomiphene/therapeutic use ; Follicle Stimulating Hormone/therapeutic use ; Gonadotropins/therapeutic use ; Hypogonadism/drug therapy ; Luteinizing Hormone/genetics ; Selective Estrogen Receptor Modulators/therapeutic use ; Spermatogenesis/drug effects ; Humans ; Male ; Fertility Agents, Male ; Tablets |
| Περίληψη: | Treatment of idiopathic male infertility has traditionally relied on the empirical use of oral agents such as clomiphene citrate and aromatase inhibitors, often prescribed without rigorous endocrine phenotyping. The newly proposed APHRODITE criteria (Addressing male Patients with Hypogonadism and/or infeRtility Owing to altereD, Idiopathic TEsticular function) introduce a biologically rational framework for stratifying infertile men and tailoring hormonal therapy. This opinion article draws a conceptual parallel with the evolution of ovarian stimulation in IVF, in which exogenous gonadotropins supplanted oral agents due to their superior physiological control and better outcomes. Similarly, the APHRODITE system may catalyze a paradigm shift in male infertility treatment-from empirical, tablet-based regimens to biology-driven gonadotropin therapy. Here, we revisit the hormonal regulation of spermatogenesis, critically appraise the limited efficacy of selective estrogen receptor modulators and aromatase inhibitors, and summarize evidence supporting gonadotropin therapy. We further highlight the potential impact of FSH and LH/hCG genetic polymorphisms on treatment responsiveness. While clomiphene citrate and aromatase inhibitors retain a role in specific endocrine profiles, the new positioning of exogenous gonadotropins-LH/hCG and FSH-as targeted, earlier-line interventions holds promise to improve outcomes and efficacy in male fertility care. Future progress will depend on prospective trials that apply the APHRODITE criteria and on comparative analyses of oral agents versus injectable gonadotropin regimens in well-defined patient phenotypes. (© The Author(s) 2026. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
| Contributed Indexing: | Keywords: APHRODITE criteria; hormonal therapy; hypogonadism; male infertility; non-obstructive azoospermia; oligozoospermia; spermatogenesis |
| Substance Nomenclature: | 0 (Aromatase Inhibitors) 1HRS458QU2 (Clomiphene) 0 (Fertility Agents, Male) 9002-68-0 (Follicle Stimulating Hormone) 0 (Gonadotropins) 9002-67-9 (Luteinizing Hormone) 0 (Selective Estrogen Receptor Modulators) 0 (Tablets) |
| Entry Date(s): | Date Created: 20260321 Date Completed: 20260605 Latest Revision: 20260730 |
| Update Code: | 20260731 |
| DOI: | 10.1093/humrep/deag041 |
| PMID: | 41863283 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1460-2350 |
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| DOI: | 10.1093/humrep/deag041 |