Aims:
Transgender women taking estrogens for gender affirming hormone therapy (GAHT) suppress spermatogenesis so sperm cryopreservation may be used to preserve fertility; however, little is known about recovery of spermatogenesis following GAHT cessation. A systematic review and meta-analysis of published studies examined the impact of GAHT on spermatogenesis and its potential for recovery after ceasing treatment.
Methods:
Medline, Embase and hand searching identified 1087 studies with 18 included after screening comprising 5 with semen analyses (SFA) and 13 histology studies. Outcomes were harmonised and pooled for analysis as weighted averages in Forest plots.
Results:
SFA data studies comprised 4 groups pre-GAHT, 2 during GAHT and 5 ceasing GAHT after a weighted average of 14 months (range 3-59).
Variable |
Pre-GAHT |
During GAHT |
Post-GAHT |
p |
Sperm output (M) |
151 [89, 214] |
38 [33, 109] |
50 [23, 77] |
0.01 (χ2) |
Semen volume (mL) |
3.1 [2.7, 3.5] |
2.0 [1.5, 2.6] |
2.7 [2.3, 3.1] |
<0.01 (χ2) |
Azoospermia was more frequent in current GAHT followed by post-GAHT groups. Azoospermia in pre-GAHT groups ranged up to 6.3%, higher than expected 1% from a background male population.
Histologically, transwomen on GAHT at orchiectomy had absent germ cells in 5-79% with more mature spermatozoa evident in a post vs current GAHT (6% vs 1%). Overall low prevalence of normal spermatogenesis was evident in pre-GAHT with the highest prevalence (11%) observed in the post-GAHT group.
Conclusion
Marked suppression of spermatogenesis and semen volume were evident in both SFA and histology studies during GAHT with recovery of semen volume and possibly sperm output after even a short period off GAHT. Longer follow-up after ceasing GAHT is warranted to evaluate the need for sperm cryostorage to preserve fertility. Limitations in study size, design and quality limit generalisability.