Table 1.
Clinical characteristics of nine trans women who stopped GAHT and their subsequent semen analyses
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Initial presentation to gender clinic | Location | The Netherlands | The Netherlands | The Netherlands | The Netherlands | The Netherlands | The Netherlands | Australia | The Netherlands | The Netherlands |
| age at first presentation to gender clinic | 26 | 18 | 25 | 28 | 26 | 32 | 28 | 26 | 27 | |
| age at diagnosis of gender dysphoria | 28 | 21 | 25 | 28 | 27 | 33 | 28 | 27 | 29 | |
| relevant medical history | left testicular torsion | androgenetic alopecia | N/A | commenced hormone treatment on own initiative after purchasing online | started hormone treatment in Lebanon; depression | N/A | N/A | N/A | used oral contraceptives for 2 months in 2012 | |
| concurrent medication | N/A | finasteride 1mg/day (for alopecia) | N/A | N/A | paroxetine 20 mg/day | N/A | N/A | N/A | N/A | |
| baseline serum hormone levels | ||||||||||
| estradiol (pmol/L) | 123 | 72 | 82 | 705 | ND | 95 | 122 | 127 | 124 | |
| testosterone (nmol/L) | 27 | 19 | 15 | <0.5 | ND | 21 | 14.8 | 29 | 33 | |
| LH (IU/L) | 2.8 | 3.6 | 2.4 | <0.1 | ND | 5.2 | 4.2 | 5.1 | 9 | |
| FSH (IU/L) | ND | ND | ND | ND | ND | ND | ND | ND | ||
| Fertility history and previous counseling | previous children | nil | nil | nil | nil | nil | nil | nil | nil | nil |
| reproductive desires prior to commencing GAHT | wish for fertility preservation, wants children in the future. | used illicitly obtained hormones, no prior fertility counseling | not discussed | used illicitly obtained hormones, no prior fertility counseling | used illicitly obtained hormones, no prior fertility counseling | no prior fertility counseling | fertility counseling was provided; not wanting children, planning to adopt; fertility preservation declined | fertility counseling was provided; declined fertility preservation | fertility counseling was provided; declined fertility preservation | |
| prior fertility preservation | semen cryopreservation: 43 vials suitable for ICSI | none | none | none | none | none | none | none | none | |
| Estrogen therapy | age started | 28 | 18 | 23 | 24 | 24 | 33 | 28 | 27 | 30 |
| agent | estradiol patches | estradiol valerate | estradiol valerate | estradiol valerate | estradiol valerate | estradiol valerate | estrodial valerate | estradiol valerate | estradiol valerate | |
| starting dose | 100 mcg/24 h twice a week | 4 mg/day | 2 mg/twice a day | 2 mg/twice a day | 2 mg/twice a day | 2 mg/twice a day | 4 mg/day | 2 mg/twice a day | 2 mg/twice a day | |
| age stopped | 31 | 18 | 41 | 32 | 27 | 36 | 29 | 33 | 33 | |
| dose at cessation | 100 mcg/24 h twice a week | 2 mg/day | estrogel 0.06% 1.25 mg twice a day | estradiol valerate 2 mg /twice a day | estradiol valerate 2 mg/day | estradiol valerate 2 mg/twice a day | 4 mg/day | estradiol valerate 2 mg/twice a day | estradiol valerate 2 mg/twice a day | |
| duration of estrogen therapy (months) | 22 | 6 | 216 | 99 | 36 | 36 | 14 | 56 (period of cessation in 2014) | 36 | |
| Anti-androgen therapy | age started | 28 | 18 | 23 | 24 | 24 | 33 | 28 | 27 | 29 |
| agent | cyproterone acetate | spironolactone | cyproterone acetate | cyproterone acetate | spironolactone | cyproterone acetate | cyproterone acetate | cyproterone acetate | cyproterone acetate | |
| starting dose | 25 mg/day | 100 mg/day | 100 mg/day | 50 mg/day | 100 mg/day | 50 mg/day | 25 mg/day | 50 mg/twice a day | 50 mg/day | |
| age stopped | 31 | 18 | 41 | 32 | 27 | 36 | 29 | 33 | 33 | |
| dose at cessation | 10 mg/day | 100 mg/day | 50 mg/day | 50 mg/day | 100 mg/day | 12.5 mg/day | 25 mg/alternate days | 20 mg/day | 50 mg/day | |
| duration on anti-androgen (months) | 17 | 6 | 216 | 93 | 36 | 36 | 14 | 56 (period of cessation in 2014) | 40 | |
| Gender affirming surgery | None | None | Breast augmentation | Breast augmentation | None | None | None | None | None | |
| Physical response to hormone treatment | physical changes | breast development, decreased muscle strength | unknown | unknown | unknown | unknown | breast development, decreased facial hair growth | Tanner stage 3-4 breast development | breast development | decreased muscle strength, decreased body hair growth, softer skin, breast development |
| subsequent serum hormone levels | ||||||||||
| timing | 20 months after commencement | ND | 204 months after commencement | 93 months after commencement | ND | 15 months after commencement | 13 months after commencement | 24 months after re-initiation of hormones | 36 months after commencement of estradiol | |
| estradiol (pmol/L) | 641 | ND | 120 | 286 | ND | 246 | 556 | 320 | 154 | |
| testosterone (nmol/L) | 0.4 | ND | 0.9 | 0.2 | ND | 4.4 | 0.9 | 0.7 | 0.4 | |
| LH (IU/L) | 0.1 | ND | 0.3 | <0.1 | ND | 1.1 | 0.2 | 1.2 | <0.1 | |
| FSH (IU/L) | n/d | ND | ND | ND | ND | ND | ND | ND | ND | |
| Cessation of anti-androgens/estrogen | rationale | wishes natural conception with new partner | wants to cryopreserve semen to keep all options open | wants to conceive with partner | wants to cryopreserve semen to keep all options open, partner has active child wish | prefers genetically related offspring over adoption | wants to conceive with partner | wants to conceive with partner | wants to cryopreserve semen to keep all options open | strong parental desire |
| physical changes after cessation | increased hair growth and higher volume of ejaculate | unknown | none, no hot flushes, no increased hair growth | acne | increased hair loss/baldness | increased facial hair growth | breast atrophy, testicular volume increase | higher volume of ejaculation, increased sexual function, increased muscle strength | increased hair growth (body and face) | |
| subsequent serum hormone levels | ||||||||||
| timing | 3 months after cessation | ND | ND | ND | 3 months after cessation | 22 months after cessation | 6 months after cessation | 7 months after cessation | 13 months after cessation | |
| estradiol (pmol/L) | 82 | ND | ND | ND | ND | ND | 164 | ND | ND | |
| testosterone (nmol/L) | 17.0 | ND | ND | ND | 18 | 11 | 18.8 | 21 | 16 | |
| LH (IU/L) | 3.1 | ND | ND | ND | ND | ND | 5.2 | 9.2 | 11 | |
| FSH (IU/L) | 9.0 | ND | ND | ND | 3.3 | 6.2 | 17.2 | 19 | 23 | |
| Semen specimen #1 after stopping hormones | time after stopping GAHT (months) | 3 | 3 | 27∗∗ | 4 | 3 | 7 | 1 | 4 | 7 |
| volume (mL) | 1.2 | 4.5∗ | 2.1∗ | 3.5∗ | 1.3 | 3.4∗ | 0.2 | unknown | 1 | |
| sperm concentration (million/mL) | 3.3 | 48∗ | 77.7∗ | 0.2 | 1.2 | 31.3∗ | 0 | 0 | 0 | |
| sperm motility (%) | 20 | 69∗ | 51∗ | 19 | 17 | 40∗ | nil | 0 | 0 | |
| Semen specimen #2 after stopping hormones | time after stopping GAHT (months) | 7 | 3 | N/A | N/A | 3 | 22 | 8 | 7 | 7 |
| volume (mL) | 1.3 | 5∗ | N/A | N/A | 1.7∗ | 1.6∗ | 1 | unknown | 2.5∗ | |
| sperm concentration (million/mL) | 3.8 | 55∗ | N/A | N/A | 0.8 | 22.3∗ | <2 | 0 | 0 | |
| sperm motility (%) | 41∗ | 55∗ | N/A | N/A | 49∗ | 63∗ | 6 | 0 | 0 | |
| Semen specimen #3 after stopping hormones | time after stopping GAHT (months) | 8 | 3 | N/A | N/A | 3 | 22 | 9 | 10 | 13 |
| volume (mL) | 4.8∗ | 6∗ | N/A | N/A | 0.9 | 2.5∗ | 2∗ | 3.2∗ | 3.2∗ | |
| sperm concentration (million/mL) | 20.2∗ | 53∗ | N/A | N/A | 0.4 | 7.1 | <2 | 9 | 0 | |
| sperm motility (%) | 48∗ | 75∗ | N/A | N/A | 56∗ | 13 | 50∗ | 44∗ | 0 | |
| Semen specimen #4 after stopping hormones | time after stopping GAHT (months) | N/A | N/A | N/A | N/A | N/A | 22 | N/A | 11 | N/A |
| volume (mL) | N/A | N/A | N/A | N/A | N/A | 2.2∗ | N/A | 2.7∗ | N/A | |
| sperm concentration (million/mL) | N/A | N/A | N/A | N/A | N/A | 21∗ | N/A | 11.8 | N/A | |
| sperm motility (%) | N/A | N/A | N/A | N/A | N/A | 43∗ | N/A | 36∗ | N/A | |
| Additional follow-up | Patient 1: Partner became pregnant 4 months after cessation of hormone treatment through natural conception Patient 3: Partner became pregnant 40 months after cessation of hormone treatment through natural conception Patient 6: Partner became pregnant 20 months after cessation of hormone treatment through natural conception Patient 9: After failing to identify any mature sperm on repeated semen specimens, further physical examination and investigations were performed. Examination revealed a right testicle volume of 2 ml, left testicle volume of 3 ml and normal consistency on both sides without any abnormalities of the epididymis or vas deferens. Scrotal ultrasound revealed: right testicle volume of 2.0 ml, left testicle volume 3.7 ml, normal testicular structure and vascularisation, normal epididymis. Karyotype was 46XY with no Y chromosome abnormalities seen. Testicular sperm extraction was subsequently performed. Complete spermatogenesis was sporadically encountered in both testicles, and mature spermatozoa were harvested 17 months after stopping hormones. |
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The single asterisk (∗) indicates that semen parameters were above the normal WHO reference range for semen volume (≥1.5 mL), sperm concentration (≥15 million/mL), or progressive motility (≥32%).
The double asterisk (∗∗) indicates that Patient 3’s first semen analysis was significantly delayed due to a move across continents, during which time she was unable to be with her partner. They were eventually reunited after which the semen analysis was performed.