Fertility Concerns of the Transgender Patient

Philip J. Cheng; Alexander W. Pastuszak; Jeremy B. Myers; Isak A. Goodwin; James M. Hotaling


Transl Androl Urol. 2019;8(3):209-218. 

In This Article

Effects of Hormone Therapy on Fertility

Effects of Puberty Suppression

Pubertal suppression with gonadotropin-releasing hormone agonist analogs (GnRHa) is used in the pediatric transgender population as early as Tanner stage 2. This treatment prevents the development of permanent secondary sex characteristics incongruent with gender identity and can alleviate the psychological distress associated with these changes.[20] Furthermore, it provides more time for these children to explore their gender identity. GnRHa-based pubertal suppression is reversible, but it also pauses maturation of germ cells, which could affect fertility potential.[21–23] In children treated with GnRHa, 43 of 49 patients had a decrease in testicular volume.[24] Similarly, a study of 87 girls with precocious puberty while on GnRHa showed a decrease in ovarian and uterine size during treatment, which subsequently increased in size with resumption of menstruation approximately 1 year after discontinuing therapy.[25]

Effects of Testosterone Therapy

Gender-affirming hormone therapy in transgender individuals may impact gonadal function and the long-term effects on future fertility are unknown. In transmen, testosterone induces amenorrhea by suppressing ovulation. There are several studies that have investigated the effect of prolonged androgen therapy on ovarian histology. One study of 112 transgender men who underwent hysterectomy with bilateral oophorectomy after testosterone therapy revealed a polycystic ovarian morphology, such as collagenization of the outer cortex, stromal hyperplasia, luteinization of stroma cells, and multifollicular ovaries.[26] In contrast, another study of 40 transgender men on testosterone for more than one year showed preservation of normal cortical follicle distribution.[15]

Effects of Estrogen Therapy

In transwomen, estrogen therapy suppresses gonadotropin levels, leading to reduced testosterone levels, which can affect spermatogenesis. The effect of GAHT on testicular morphology in transwomen who underwent orchiectomy has been described in 11 studies with variable hormonal treatment regimens.[27] Similar to the studies on the effect of testosterone therapy in transmen, these studies showed conflicting results. Outcomes ranged from complete cessation of spermatogenesis with testicular atrophy, hyalinization, and fibrosis to preserved spermatogenesis with normal testicular histology.[27–31] Outcomes of one study by Schneider et al. were heterogeneous irrespective of whether patients discontinued hormones 6 weeks before orchiectomy, 2 weeks before, or not at all, with 24% of patients demonstrating normal spermatogenesis, while the rest had varying degrees of impairment, such as meiotic arrest or spermatogonial arrest.[30] Revirilization occurred quickly in the patients who had stopped hormones.[30] In another study that evaluated the effect of duration of hormone therapy, there was a trend toward worse spermatogenesis with longer therapies, but this was not statistically significant.[31]

In the first study to describe the impact of GAHT on semen parameters, Adeleye et al. evaluated a cohort of 28 transwomen who presented for sperm cryopreservation.[32] The authors compared 18 patients who had never used hormones, 3 who had discontinued hormones before specimen collection (mean discontinuation period of 4.4 months), and 7 who had continued hormones at the time of specimen collection. There were significant differences in concentration, motility, and total motile sperm count between the three groups; the hormone-naïve patients had the best semen parameters. Three of the patients who had continued hormones were azoospermic while all patients who had discontinued hormones had semen analysis parameters that were within normal limits based on World Health Organization (WHO) reference values.[32]