Recovery of spermatogenesis in transwomen after established gender-affirming hormone therapy — ASN Events
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Recovery of spermatogenesis in transwomen after established gender-affirming hormone therapy (#306)

Sharanya Mohan 1 , Sarina Lim 1 , Veena Jayadev 1 , David J Handelsman 1 2
  1. Andrology, Concord Hospital, Concord, NSW, Australia
  2. ANZAC Research Institute, Concord, NSW, Australia

Background: Transgender and gender diverse individuals including transgender women (TW) often retain a desire for procreation [1]. Gender affirming hormone therapy (GAHT) suppresses spermatogenesis, hence, sperm cryostorage is encouraged prior to GAHT. Uptake remains poor so some TW may subsequently seek fertility after established GAHT [2]. However, the potential and extent of recovery of sperm after GAHT is not well understood.

Methods: A literature review (PubMed) of sperm outcomes after at least 4 weeks of suspended GAHT identified seven ejaculated sperm studies [3-9] and seven studies on orchidectomy specimens [10-16].

Results: GAHT impairs sperm concentration, motility and cryosurvival compared to control men and TW not on GAHT [5, 8]. In TW after ceasing GAHT, semen (37.5 - 100%) and orchidectomy samples (3.7-50%) displayed recovery of sperm production. Yet, despite reduced sperm output, 78-100% of fresh samples and 38-93% of thawed samples were sufficient for intrauterine insemination or in-vitro fertilisation. Recovery trajectory is heterogeneous with partial recovery within 1–3 months, additional recovery by 6–12 months, and delayed recovery beyond 12 months in some.

Histological recovery of spermatogenesis was best predicted by testicular volume [15]. Spermatogenesis is more impaired by cyproterone acetate and estradiol exposure in adults than GnRH-analog in adolescents [17]. Neither serum or intratesticular testosterone concentrations nor duration of GAHT were reliable indicators of recovery. Initiating GAHT in early puberty (Tanner 2-3) is associated with poorer recovery compared to commencement at later stages (Tanner 4-5) [17]. Overall, the small sample size and heterogeneity in treatments limited analysis of the specific effects of anti-androgen, estradiol or progesterone.  

Conclusion: Spermatogenesis may recover within months after cessation of GAHT in some individuals but up to 6–12 months in others. Even partial recovery can facilitate fertility through assisted reproductive techniques.

  1. Maiorano, M.F.P., Cormio, G., Loizzi, V., Maiorano, B.A., Arezzo, F., Silvestris, E., Fertility preservation for transgender and non-binary individuals: a systematic review and thematic synthesis of clinical, psychosocial, and structural challenges. Human Fertility, 2025. 28(1).
  2. Stolk, T.H.R., Asseler, J.D., Huirne, J.A.F., van den Boogaard, E., van Mello, N.M., Desire for children and fertility preservation in transgender and gender-diverse people: A systematic review. Best Practice & Research. Clinical Obstetrics & Gynaecology, 2023. 87(102312).
  3. Adeleye A.J., R.G., Kao C.N., Mok-Lin E., Smith J.F. , Semen parameters among transgender women with a history of hormonal treatment. Urology, 2019. 124: p. 136–141.
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  6. Barnard, E.P., Dhar, C. P., Rothenberg, S. S., Menke, M. N., Witchel, S. F., Montano, G. T., Orwig, K. E., & Valli-Pulaski, H. , Fertility preservation outcomes in adolescent and young adult feminizing transgender patients. Pediatrics, 2019. 144 (3): p. e20183943.
  7. de Nie, I., van Mello, N.M., Vlahakis, E., Cooper, C., Peri, A., den Heijer, M., Meibner, A., Huirne, J., Pang, K.C., Successful restoration of spermatogenesis following gender-affirming hormone therapy in transgender women. Cell Rep. Med., 2023. 3: p. 100858-1–100858-7.
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  11. Jindarak S, N.K., Atikankul T, Angspatt A, Pungrasmi P, Iamphongsai S, Promniyom P, Suwajo P, Selvaggi G, Tiewtranon P, Spermatogenesis Abnormalities following Hormonal Therapy in Transwomen. Biomed Res Int, 2018: p. 7919481.
  12. Peña Barreno, C., Gonzalez-Peramato, P., Nistal, M. , Vascular and inflammatory effects of estrogen and anti-androgen therapy in the testis and epididymis of male to female transgender adults. Reprod Toxicol, 2020. 95: p. 37–44.
  13. Ponte, R., Dupuy, F.P., Brimo, F., Mehraj, V., Brassard, P., Belanger, M., Yurchenko, E., Jenabian, M.A., Bernard, N.F., Routy, J.P. , Characterization of myeloid cell populations in human testes collected after sex reassignment surgery. . J Reprod Immunol, 2018. 125: p. 16-24.
  14. Schneider, F., Dabel, J., Sandhowe-Klaverkamp, R., Neuhaus, N., Schlatt, S., Kliesch, S., Wistuba, J., Serum and intratesticular inhibin B, AMH, and spermatogonial numbers in trans women at gender-confirming surgery: An observational study. Andrology, 2021. 9(6): p. 1781-1789.
  15. Schneider F, N.N., Wistuba J, Zitzmann M, Heß J, Mahler D, van Ahlen H, Schlatt S, Kliesch S, Testicular Functions and Clinical Characterization of Patients with Gender Dysphoria (GD) Undergoing Sex Reassignment Surgery (SRS) The Journal of Sexual Medicine, 2015. 12(11): p. 2190–2200.
  16. Thiagaraj, D., Gunasegaram, R., Loganath, A., Peh, K. L., Kottegoda, S. R., & Ratnam, S. S., Histopathology of the testes from male transsexuals on oestrogen therapy. Annals of the Academy of Medicine, Singapore, 1987. 16(2): p. 347-348.
  17. de Nie, I., Mulder, C.L., Meißner, A., Schut, Y., Holleman, E.M., van der Sluis, W.B., Hannema, S.E., den Heijer, M., Huirne, J., van Pelt, A.M.M., van Mello, N.M., Histological study on the influence of puberty suppression and hormonal treatment on developing germ cells in transgender women. Human Reproduction, 2022. 37(2): p. 297-308.