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Gender-Affirming Hormone Therapy (GAHT)

Gender-affirming hormone therapy (GAHT) encompasses feminizing regimens (estrogen ± antiandrogens) and masculinizing regimens (testosterone) used to align physical characteristics with gender identity. The Endocrine Society 2017 and WPATH SOC 8 provide GAHT recommendations for eligible people, and ACOG describes hormone therapy as medically necessary for many people with gender dysphoria.[1][2][3][4][26] In adults seeking GAHT, a 2025 review identified one low-certainty randomized trial and 12 longitudinal studies with serious-to-critical bias that suggested possible improvements in depression, quality of life, and suicidality; a 64-person, 3-month randomized trial of immediate versus delayed testosterone found lower gender dysphoria in the immediate group.[47][48]

This article is the pharmacology reference for the reconstructive urologist and urogynecologist who participates in GAHT-management decisions perioperatively or longitudinally. For surgical detail, see Gender-Affirming Surgery overview. For related hormonal-therapy topics, see Testosterone replacement, Vaginal and topical estrogen, and Androgen adjuncts.

Feminizing GAHT — estrogen ± antiandrogen​

Estrogen formulations​

The primary agent is 17β-estradiol. SOC 8 recommends against ethinyl estradiol (statement 12.13) and suggests not prescribing conjugated estrogens when estradiol is available (12.15).[26] Historical cohorts using older regimens reported high VTE rates, but the approximately 20-fold signal is not a direct modern head-to-head estimate for ethinyl versus transdermal estradiol.[26][1][5][3]

FormulationDoseRouteNotes
Oral estradiol2–6 mg/day, individualized gradual titrationPOMost commonly prescribed; SOC 8 suggests transdermal estradiol for patients age >45 or with prior VTE, while contemporary oral-versus-transdermal 17β-estradiol event estimates remain uncertain[1][5][26]
Transdermal estradiol0.025–0.2 mg/24 h patch, changed every 3–5 days[1][26]TransdermalSOC 8 suggests it for age >45 or a previous VTE (12.14); smoking and obesity are modifiable thromboembolic risk factors to address[26][5]
Estradiol valerate2–10 mg IM weekly or 5–30 mg IM every 2 weeks (Endocrine Society 2017 and SOC 8 list valerate or cypionate together; titrate to avoid excessive peaks)IM / SC (the cited guideline dose is IM; SC use is also described)[40]Peak/trough variation; comparative VTE risk is not established[1][26]
Estradiol cypionateSame IM regimen as valerate (2–10 mg weekly or 5–30 mg every 2 weeks)IM / SC (the cited guideline dose is IM; SC use is also described)[41]Similar to valerate[1][26]
Ethinyl estradiol——Do not use (SOC 8 recommendation 12.13); thrombotic risk is higher and estradiol assays do not monitor it[1][26][3]
Conjugated estrogens——SOC 8 suggests not prescribing them when estradiol is available (12.15); doses cannot be regulated by serum levels[1][26][3]

Target serum levels (Endocrine Society):[1][5]

  • Estradiol 100–200 pg/mL (wider range may be acceptable for individual goals)
  • Testosterone <50 ng/dL

A 2025 systematic review of 49 studies found no evidence that keeping estradiol within the 100–200 pg/mL guideline range predicts feminizing sufficiency, testosterone suppression, or toxicity better than levels outside it.[32]

Antiandrogen agents​

Physiologic estrogen doses alone are usually insufficient to suppress testosterone into the female range. SOC 8 recommends a testosterone-lowering medication (cyproterone acetate, spironolactone or a GnRH agonist) when the goal is to approximate cisgender female hormone concentrations (12.16), and it does not favor one agent over another.[1][26]

AgentDoseMechanismKey considerations
Spironolactone100–300 mg/day (Endocrine Society 2017 and SOC 8 range)[1][26]AR antagonist; weak T-synthesis inhibitorMost commonly prescribed testosterone-lowering agent in the US; monitor K⁺ and creatinine (hyperkalemia rare in healthy adults); weak estrogenic activity[26][1][5][3]
Cyproterone acetate25–50 mg/day in Endocrine Society 2017; 10 mg/day in SOC 8, which uses the lowest effective dose[1][26]Progestational antiandrogen; suppresses gonadotropinsUsed in some non-US settings; not approved in the US. SOC 8 notes a meningioma signal with use beyond 2 years and doses above 10 mg/day, and the EMA restricts 10 mg/day or higher products for hirsutism, androgenic alopecia, acne and seborrhoea after other treatments fail; hepatotoxicity requires attention[28][1][4]
GnRH agonists (leuprolide, goserelin)Product- and indication-specific depot dosingSuppress LH/FSH → profound T suppressionVery effective suppression; very expensive in US; used by specialist teams for puberty suppression; adult depot schedules are not automatically pediatric schedules[1][5]
Finasteride1–5 mg/day5α-reductase inhibitor (T → DHT block)Does not lower T. SOC 8 does not recommend routine use in transfeminine people whose T and DHT are already lowered; data are sparse[1][26]
Progesterone / progestinsVariableGonadotropin suppressionAnecdotal breast-development and mood benefit; no well-designed studies; MPA has WHI CV signal[6]

Timeline of feminizing changes[26][1]​

Onset and maximum effect follow SOC 8 Appendix C Table 1; the Endocrine Society 2017 estimates are the same except where noted.

ChangeOnsetMax effectReversibility
Breast growth3–6 mo2–5 y (2–3 y in Endocrine Society 2017)Irreversible
Decreased sexual desire1–3 moUnknown (SOC 8)Reversible
Decreased spontaneous erections1–3 mo3–6 moReversible
Skin softening / ↓ oiliness3–6 moUnknownReversible
Fat redistribution (female)3–6 mo2–5 yReversible
Decreased terminal body / facial hair6–12 mo (Endocrine Society 2017)>3 y (complete removal needs electrolysis or laser)Reversible
Decreased muscle mass / strength3–6 mo1–2 yReversible
Testicular-volume reduction3–6 moVariable in SOC 8; 2–3 y in Endocrine Society 2017Recovery and fertility after cessation are variable; not guaranteed
Decreased sperm productionUnknown2 y in SOC 8; >3 y in Endocrine Society 2017Recovery is variable
Scalp hairVariable—Familial scalp hair loss may occur if estrogen is stopped (Endocrine Society 2017)
Voice——N/A — estrogen does not raise pitch; speech therapy required

Masculinizing GAHT — testosterone​

Regimens mirror the treatment of male hypogonadism and target the normal physiologic male range.[1][26] See also Testosterone replacement for the underlying pharmacology.

Testosterone formulations​

FormulationDoseRouteNotes
Cypionate50–100 mg SC/IM weekly (or 100–200 mg q2 wk)SC or IMUS first-line; SC increasingly preferred (smaller needle, less pain)[5][3]
Enanthate50–100 mg SC/IM weekly (or 100–200 mg q2 wk)SC or IMInterchangeable with cypionate[1][5]
UndecanoateUS AVEED: 750 mg IM at baseline, 4 weeks, then every 10 weeks; 1,000 mg regimens belong to other products/jurisdictionsIM onlyUS REMS; observe 30 minutes after every AVEED injection for POME/anaphylaxis. GAHT use is off-label.[27]
Transdermal gel / patchGel 50–100 mg/d; patch 2.5–7.5 mg/dTransdermalMore uniform levels; titrate to clinical goals and measured levels; transfer risk to contacts[1][5]
PelletsTESTOPEL label for androgen-deficient males: 150–450 mg SC every 3–6 months[42]; one 30-person retrospective transmasculine series used 675–825 mg per cycle with dose adjustment by measured testosterone[43]SC implantLess common; requires minor procedure[42][43]. In that 30-person retrospective series, hematocrit ≥50% was recorded in 14/30 (46.7%), including 5 with elevated hematocrit before switching to pellets, and pellet extrusion in 4/30 (13.3%).[43]

Target serum levels:[1][26]

  • Testosterone in the physiologic male range; for cypionate or enanthate, measure midway between injections (target 400–700 ng/dL). SOC 8 advises measuring injectable undecanoate before the next injection and adjusting the interval if testosterone is <400 ng/dL; the US AVEED label specifies 750 mg at baseline, week 4, then every 10 weeks without dose titration.[26][27]
  • Avoid supraphysiologic levels (erythrocytosis, acne, adverse lipid profile)

Timeline of masculinizing changes[26][1]​

Onset and maximum effect follow SOC 8 Appendix C Table 1; Endocrine Society 2017 differences are noted. Neither guideline gives the reversibility column.

ChangeOnsetMax effectReversibility
Cessation of menses1–6 mo1–2 y in SOC 8Reversible
Clitoral enlargement1–6 mo1–2 yIrreversible
Voice deepening1–6 mo in SOC 8; 6–12 mo in Endocrine Society 20171–2 yIrreversible
Facial / body hair growth6–12 mo>5 y in SOC 8; 4–5 y in Endocrine Society 2017Irreversible
Increased muscle mass6–12 mo2–5 yReversible
Fat redistribution (male)1–6 mo2–5 yReversible
Acne1–6 mo1–2 yReversible
Increased libido——Reversible
Scalp hair loss (male-pattern)6–12 mo>5 y in SOC 8Irreversible (genetic)
Vaginal atrophy1–6 mo1–2 yReversible

Persistent uterine bleeding requires assessment of adherence, hormone levels, pregnancy risk, and other gynecologic causes. The Endocrine Society 2017 guideline says clinicians may consider adding a progestational agent or endometrial ablation. GnRH analogs or depot medroxyprogesterone can be given to stop menses before testosterone is started. Ablation requires separate fertility and procedural counseling.[1]

Obstructive sleep apnea. A small case series reported two transgender men with new-onset obstructive sleep apnea after testosterone initiation despite no recorded change in BMI or neck size, alongside a third case of OSA resolving in a transgender woman after starting feminizing therapy. Testosterone can induce or worsen OSA in cisgender men; OSA risk during masculinizing GAHT remains unquantified. Assess and manage sleep apnea individually: SOC 8 lists sleep apnea, severe hypertension and polycythemia as relative contraindications, and pregnancy or attempted conception as a contraindication to testosterone.[38][26]

Puberty suppression in adolescents​

GnRH agonists can suppress further pubertal development from Tanner stage 2 in eligible adolescents after specialist assessment and individualized informed consent. Adult GAHT regimens should not be used as pediatric prescribing instructions.[26][1][7][8]

Rationale​

  • Prevents irreversible development of undesired secondary sex characteristics (breast development, voice deepening, facial hair, skeletal changes)
  • Extends the diagnostic window for gender-identity exploration
  • May relieve distress from unwanted pubertal changes; psychological outcome estimates come mainly from observational studies
  • Surgical planning. In a 300-person cohort, puberty suppression was associated with less invasive or omitted mastectomy in transmasculine participants; among transfeminine participants starting at Tanner 2/3, mean penile length was 4.8 cm shorter than in unsuppressed controls, and the odds of intestinal vaginoplasty were higher (odds ratio 84).[50]

Key considerations​

  • Suppression of the hypothalamic-pituitary-gonadal axis is reversible after stopping.
  • Bone accrual and monitoring. A 2026 meta-analysis of 10 cohorts (751 adolescents) found stable absolute lumbar-spine BMD but declining age-adjusted z scores during GnRHa suppression, followed by rising BMD and partial z-score recovery after GAHT; the Endocrine Society 2017 protocol uses DXA every 1–2 years during suppression.[49][1]
  • Fertility implications. GnRHa inhibits spermatogenesis and ovulation; fertility preservation counseling before initiation
  • Growth. Height velocity slows during treatment; final height generally within genetic target

Signal from real-world data​

Nos 2022 (JAMA Network Open) included 434 adolescents, 70 of whom received GnRHa. Median time to GAHT was 1.8 versus 1.0 years with versus without GnRHa. The authors concluded that GnRHa use was not associated with increased subsequent GAHT use.[9]

Cardiovascular and thromboembolic risk — the dominant safety concern​

Feminizing GAHT — VTE​

Transfeminine persons on estrogen have higher VTE incidence than cisgender women or cisgender men; risk varies by age, formulation, exposure duration, and baseline factors. Much of the historical signal reflects ethinyl estradiol, which is no longer recommended. Transdermal estradiol is favored when baseline VTE risk is elevated, although the size of any clinical-event advantage over contemporary oral 17β-estradiol in GAHT remains uncertain.[10][26]

van Zijverden2025 online/2026 print Dutch cohort (n = 2,714 transfeminine; 23,907 person-years):[11]

  • MI: SIR 0.50 (95% CI 0.32–0.71), lower than general-population men[11]
  • Stroke: SIR 0.94 (0.72–1.19), similar
  • VTE: SIR 1.81 (1.33–2.35), higher

Masculinizing GAHT — CV​

Same Dutch cohort (n = 1,617 transmasculine; 13,457 person-years):[11]

  • MI: SIR 4.20 (2.72–6.01), significantly higher than general-population women
  • Stroke: SIR 1.55 (1.01–2.20), higher
  • VTE: SIR 1.00 (0.53–1.61), similar

Testosterone is also associated with erythrocytosis (most common AE), adverse lipid profile (↓HDL, ↑LDL), and higher BP.[1][3][12]

Older perioperative standards stopped hormones for about 1–4 weeks before and after genital surgery to limit VTE risk; SOC 8 notes this rested on no direct evidence and that VTE rates were not higher when hormones were continued. Use current multidisciplinary guidance for the individual operation.[13][26]

Risk-mitigation​

  • Transdermal estradiol over oral for age >45, smokers, BMI >30, VTE risk[5][10]
  • Avoid ethinyl estradiol (SOC 8 recommendation) and conjugated estrogens when estradiol is available (SOC 8 suggestion)[1][26][10]
  • Smoking cessation strongly encouraged[5]
  • Monitor hematocrit or hemoglobin in patients on testosterone (SOC 8 recommendation 12.17). The Endocrine Society 2017 guideline classifies hematocrit >50% as erythrocytosis during testosterone therapy; its table does not state a GAHT cessation threshold.[1] The 2018 hypogonadism guideline stops testosterone above 54%.[26][1][31]
  • Individualize perioperative hormones with the surgeon and prescriber. SOC 8 does not support a universal perioperative interruption (older standards used 1–4 weeks before and after surgery); weigh VTE risk, prophylaxis and withdrawal effects, particularly after gonadectomy, where continuous sex-steroid replacement protects bone and mood. In one single-center series of 183 transfeminine patients having genital surgery, about 75% continued estradiol perioperatively under an individualized risk algorithm (those who held it for 2–6 weeks were older with higher Caprini scores); one VTE occurred in the continuation group, and no statistically significant difference in postoperative complication rates was detected.[26][30]
  • Standard CV risk-factor management (lipids, BP, diabetes screening)[1][12]

Monitoring protocols​

Feminizing GAHT[1][5]​

ParameterFrequencyTarget / action
Serum estradiolq3 mo × 1 y, then 1–2×/y100–200 pg/mL
Serum testosteroneq3 mo × 1 y, then 1–2×/y<50 ng/dL
Potassium and creatinine (if on spironolactone)Potassium: q3 mo × 1 y, then annually (Endocrine Society 2017)[1]; creatinine: monitor, with no interval specified by SOC 8Monitor for hyperkalemia and renal function[26]
ProlactinEndocrine Society 2017: baseline, at least annually during transition, then every 2 years[1]. SOC 8 makes no recommendation for or against; individualize by regimen and symptomsPituitary imaging if levels rise persistently despite stable or reduced estrogen[1][26]
Fasting lipids, glucose / HbA1cBaseline then periodicallyStandard CV-risk assessment
LHConsider at follow-upsHelps assess gonadal suppression
CBCBaseline then annuallyHemoglobin may decrease
BMDConsider at baseline; age 60 if low-risk or if not adherent to hormones; measure when risk factors exist, specifically after stopping hormones following gonadectomyOsteoporosis screening

Masculinizing GAHT[1][5]​

ParameterFrequencyTarget / action
Serum testosteroneq3 mo until at goal, then 1–2×/y400–700 ng/dL (midway between ester injections; just before the next undecanoate injection)
Hematocrit / hemoglobinBaseline, then q3 mo × 1 y, then 1–2×/yEndocrine Society 2017 classifies Hct >50% as erythrocytosis; at Hct >54%, the 2023 IDEA consensus advises excluding other causes and considering a lower testosterone dose, a longer dosing interval, or a transdermal formulation.[1][51]
Fasting lipidsBaseline then periodically↓ HDL, ↑ LDL / TG expected
Weight, BPEvery visitHypertension and weight gain surveillance
BMDIf T discontinued, non-compliant, or risk factorsOsteoporosis screening
Cervical screening (if cervix present)Per ACOGInadequate Pap tests are more frequent in transmasculine patients; testosterone-associated atrophy and examination barriers may contribute. Discuss self-collected HPV where available[3]

Cancer screening — screen organs present, not identity​

Screening is based on the anatomy present, regardless of gender identity.[14][15][16]

Breast​

  • Transfeminine. An older Dutch cohort estimated breast cancer incidence at 4.1 per 100,000 person-years in transfeminine patients versus 155 in cisgender women; breast cancer risk was higher than in cisgender men. The older Dutch estimate[2] predates a nationwide cohort spanning historical and recent hormone regimens: among 2,260 hormone-treated trans women, 15 invasive breast cancers occurred over 33,991 person-years (44.1 per 100,000 person-years), with invasive-cancer standardized incidence ratios of 46.7 versus Dutch cisgender men and 0.3 versus Dutch cisgender women; three noninvasive cancers were recorded separately.[52] For transgender and gender diverse people who have received estrogens, follow local breast screening guidelines developed for cisgender women (WPATH SOC 8 statement 15.6), taking into account duration of hormone use, dose, current age and age at initiation; the Endocrine Society 2017 suggests these guidelines for transgender women with no known increased breast-cancer risk (recommendation 4.5).[1][26] For average-risk transfeminine patients aged ≥40 with ≥5 years of hormone use, ACR says mammography or DBT may be appropriate.[29] In a selected mammography series of 50 transgender women (48 with breast augmentation), 60% had dense or very dense breasts; the authors noted that implants made mammography technically challenging.[14][15][44] A review of 18 publications described 22 breast-cancer cases in transgender women; median age at diagnosis was 51.5 years, and seven cases reported a positive family history, including one BRCA2 carrier.[37]
  • Transmasculine. If breast tissue remains (reduction mammoplasty, not mastectomy), follow cisgender female guidelines. After bilateral mastectomy and reconstruction, ACOG finds limited data supporting routine clinical chest examination without patient concern[2]; after bilateral mastectomy, ACR rates routine screening imaging as usually not appropriate[29]; evaluate new symptoms or palpable findings and consider inherited risk separately[15].

Cervical​

All individuals with a cervix should follow standard screening guidelines. Transmasculine patients have lower screening rates due to discomfort and structural barriers; testosterone-associated atrophy and examination barriers may contribute to more inadequate Pap tests. Self-collected HPV testing may improve adherence: in one transmasculine primary-care clinic, documented screening rose from 30/121 (25%) before self-swabbing was offered to 98/193 (51%) afterward.[14][3][56] For eligible asymptomatic average-risk patients with a cervix, 2025 Enduring Consensus guidance accepts FDA-approved self-collected vaginal HPV testing in health care settings for primary screening while preferring clinician-collected cervical specimens (AII).[57]

Prostate​

Gender-affirming vaginoplasty leaves the prostate in place; radical prostatectomy after vaginoplasty has been reported.[54] In a VHA series of 210 transgender women aged 40–80 who had received estrogen for at least six months, median PSA across 852 tests was 0.02 ng/mL.[45] PSA 1ng/mL is a proposed concern threshold in androgen-suppressed patients; rising PSA warrants attention.[17] Standard age-appropriate shared decision-making applies.[14][16][17]

In a Dutch cohort of 2,306 orchiectomized transgender women followed for a mean of 21.4 years (51,173 person-years), one prostate cancer was diagnosed (0.04% cumulative proportion; 0.13% among those starting hormones at age 40 or older).[34] The role of estrogen in prostate cancer is not settled, and androgen-deprivation therapy may not be protective against every prostate cancer.[35]

Testicular​

A 2018 systematic review of 43 studies reported one testicular cancer case in transgender women.[36] In a Dutch nationwide cohort of 3,026 trans women starting GAHT, two symptomatic testicular cancers occurred during median 2.3 years of follow-up (SIR 0.8, 95% CI 0.1–2.8 versus cisgender men); an additional tumor was found in 1/722 orchiectomy specimens examined.[60] After bilateral orchiectomy, there are no testes to screen. For asymptomatic people who retain testes, the general-population USPSTF recommendation against routine testicular-cancer screening is an anatomy-based extrapolation from guidance written for adolescent and adult males.[46] Testosterone that remains persistently elevated despite adequate suppression therapy should prompt consideration of a testicular tumor.

Fertility preservation — counsel before initiating​

Transfeminine​

  • Estrogen with antiandrogens causes increased sperm abnormalities, reduced count and motility, or azoospermia. Spermatogenesis may partially recover after cessation but is not guaranteed[18][19]
  • In a single-center study of 141 orchiectomy specimens from 72 transgender women after more than 1 year of GAHT, germ cells were present in 114/141 (81%) and spermatids, a histologic proxy for spermatogenesis, in 57/141 (40%).[33] Sperm banking remains an option to discuss after GAHT: a separate semen study found motile sperm in selected patients after treatment discontinuation.[39]
  • A separate comparison of semen parameters in 28 transgender women reported total motile sperm counts of 63.2 million with no prior feminizing hormone therapy, 39.1 million in 15 specimens after discontinuation (mean interval 4.4 months), and 0.2 million with continued therapy; these are group medians.[39] Stopping hormone therapy can itself cause distress; long-term gamete competence and pregnancy or live-birth outcomes after feminizing hormone exposure remain unknown[39]
  • Sperm cryopreservation should be offered before starting GAHT[4][20]

Transmasculine​

  • Testosterone causes ovarian cortical / stromal changes but persistent folliculogenesis is observed in most studies. Successful oocyte stimulation, fertilization, and live birth have been reported both with and without T discontinuation[18]
  • Oocyte or embryo cryopreservation should be offered before starting GAHT[4][20]
  • Testosterone is not reliable contraception. Pregnancies have occurred during T therapy[4]
  • Discontinue T before a planned pregnancy until after delivery and any chest-feeding[4]

Urologic considerations​

Feminizing GAHT​

  • Decreased erectile function and testicular atrophy are expected[5]
  • In a nine-patient prostate-specimen series, the two benign specimens from transfeminine patients on GAHT showed diffuse glandular atrophy and basal-cell hyperplasia.[55]
  • After vaginoplasty, shortening the urethra is generally uneventful.[21] A systematic review of 27 penile-inversion vaginoplasty studies (3,388 patients) reported pooled rates of 11.7% for poor or splayed stream, 6.9% for meatal stenosis, 11.5% for irritative symptoms, and 5.1% for retention requiring catheterization.[58]

Masculinizing GAHT​

  • Testosterone-associated vulvovaginitis. For transmasculine patients on testosterone with dryness, dyspareunia, irritation, dysuria, or bleeding, BASHH 2026 recommends offering examination to assess infection and dermatoses (grade 1D) and, when infection is excluded and the history or examination supports atrophic vulvovaginitis, off-label topical vaginal estrogen (grade 1D).[53]
  • da Silva 2024 cross-section (n = 68 transmasculine on T): 94.1% reported at least one pelvic-floor symptom. Storage symptoms were 69.1%, sexual dysfunction 52.9%, anorectal symptoms 45.6%, urinary incontinence substantial[22]
  • After phalloplasty, urethral lengthening drives fistulae, strictures, meatal stenosis, and post-voiding dribble; see the reconstructive literature[21]

Bone health​

  • Feminizing: adequate estrogen maintains BMD. The Endocrine Society 2017 guideline recommends BMD measurement when risk factors exist, specifically after stopping hormones following gonadectomy (Strong, recommendation 4.4). Table 15 also lists baseline testing as an option and screening at age 60 if low-risk[1]
  • Masculinizing: adequate testosterone maintains BMD. Screen if T discontinued, non-compliant, or other risk factors[1]
  • GnRHa in adolescents: BMD Z-scores can decline during suppression; subsequent recovery varies, and long-term skeletal outcomes need continued follow-up[8]

Drug interactions​

InteractionEffectPractical
Ritonavir-boosted PI antiretroviralsEstradiol may increase or decrease; testosterone may increaseMonitor clinical response and hormone levels[23]
Cobicistat-boosted PI antiretroviralsEstradiol and testosterone may increaseMonitor clinical response and hormone levels[23]
NNRTIs (efavirenz, etravirine, nevirapine)May decrease both estradiol and TSame — monitor[23]
Spironolactone + ACE-I / ARB / K⁺ supp / NSAIDsHyperkalemiaMonitor K⁺[1]
SmokingIncreases VTE risk synergistically with estrogenStrongly encourage cessation[5]
PerioperativeHormone interruption depends on procedure and individual risk; a 2026 genital-surgery Delphi panel reached no consensus on testosterone suspensionCoordinate hormone plans and VTE prophylaxis[26][59]

Mental-health outcomes​

Observational studies have reported associations between GAHT and:[24]

  • Lower depressive and anxiety symptoms and suicidal ideation
  • Improved global psychological functioning
  • Improved QoL and body satisfaction
  • Reduced gender dysphoria

The 2019 NEJM review (Safer & Tangpricha) summarized that gender-affirming care, including hormone therapy, is supported by multiple medical societies as medically necessary treatment that improves well-being.[3]

Evidence Summary​

DomainEvidence levelKey source
Guideline frameworkProfessional guidance; recommendation-specific certaintyEndocrine Society 2017[1]; WPATH SOC 8[26]; ACOG 2021[2]
Feminizing regimens and targetsLevel 2Goldstein 2025[5]; Safer 2019[3]
Masculinizing regimens and targetsLevel 2Endocrine Society[1]; Irwig 2017[25]
Puberty suppressionLevel 2Tornese 2025 SR[8]; Nos 2022[9]
CV and VTE riskLevel 2 (large cohort)van Zijverden2025 online/2026 print Dutch cohort[11]; Skeith 2026 NEJM review[10]
Fertility preservationLevel 2De Roo 2025 systematic review[18]
Pelvic-floor dysfunction on testosteroneLevel 3da Silva 2024[22]
Cancer screeningLevel 3 (consensus)Leone 2023 JAMA Oncol[14]; NCCN[15][17]

Clinical Positioning​

  • Use 17β-estradiol. SOC 8 recommends against ethinyl estradiol and suggests against conjugated estrogens when estradiol is available. The historical VTE signal largely traces to ethinyl estradiol, and monitoring requires 17β-estradiol assays.[1][10]
  • Prefer transdermal estradiol in patients >45 y or with a previous VTE (SOC 8 suggestion); smoking and BMI >30 are additional reasons to prefer it. Oral is acceptable in low-risk patients, with full informed consent.[26][5][10]
  • Spironolactone is the most commonly prescribed antiandrogen in the US; GnRH agonists are very effective for T suppression; cyproterone is prescribed most often in the rest of Europe, is not available in the US and carries meningioma and hepatotoxicity flags. SOC 8 does not favor one agent over another.[1][26]
  • Testosterone in transmasculine adults aims for the physiologic male range. Target 400–700 ng/dL midway between ester injections; hematocrit or hemoglobin is monitored throughout.[1][26]
  • Testosterone is NOT contraception. Counsel explicitly and provide contraception separately if pregnancy avoidance is desired.[4][5]
  • Fertility-preservation counseling must precede GAHT initiation. Sperm cryopreservation (transfeminine) or oocyte / embryo cryopreservation (transmasculine). See Androgen adjuncts for endocrine approaches studied mainly in other infertility settings; their role in fertility recovery after feminizing GAHT is unestablished.[4][18]
  • Cancer screening follows anatomy, not identity. Prostate, cervix, and breast all require organ-based screening. PSA interpretation must account for androgen suppression; no universally validated threshold exists.[14][16]
  • Risk differs by event and comparator. The Dutch observational cohort shows a roughly 4× MI-risk elevation in transmasculine patients (versus cis women) and a roughly 1.8× VTE-risk elevation in transfeminine patients (versus general-population men). Actively manage traditional CV risk factors alongside GAHT.[11][12]
  • Perioperative management requires a joint plan, including hormone formulation, prior VTE, immobility, prophylaxis, and effects of withdrawal.[26]
  • Ask about pelvic-floor and genital symptoms and treat the identified condition.[22]
  • Adolescent treatment needs specialist assessment, fertility counseling, and discussion of uncertainty.[9]
  • Monitoring cadence is q3 months in year 1, then 1–2×/year for both feminizing and masculinizing regimens, with the parameters above.[1][5]

See Also​

References​

1. Hembree WC, Cohen-Kettenis PT, Gooren L, et al. "Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline." J Clin Endocrinol Metab. 2017;102(11):3869–3903. doi:10.1210/jc.2017-01658

2. American College of Obstetricians and Gynecologists. ACOG Committee on Health Care for Underserved Women. "Health care for transgender and gender diverse individuals: ACOG Committee Opinion, Number 823." Obstet Gynecol. 2021;137(3):e75–e88. doi:10.1097/AOG.0000000000004294

3. Safer JD, Tangpricha V. "Care of transgender persons." N Engl J Med. 2019;381(25):2451–2460. doi:10.1056/NEJMcp1903650

4. Dakkak M, Kriegel DL, Tauches K. "Caring for transgender and gender-diverse people: guidelines from WPATH." Am Fam Physician. 2023;108(6):626–629. PMID 38215433

5. Goldstein Z, Krasowski MD, Greene DN. "Gender-affirming feminizing hormone therapy." JAMA Intern Med. 2025;185(8):1027–1028. doi:10.1001/jamainternmed.2025.1161

6. Crandall CJ, Mehta JM, Manson JE. "Management of menopausal symptoms: a review." JAMA. 2023;329(5):405–420. doi:10.1001/jama.2022.24140

7. Turban JL, Thornton J, Ehrensaft D. "Biopsychosocial assessments for pubertal suppression to treat adolescent gender dysphoria." J Am Acad Child Adolesc Psychiatry. 2025;64(1):12–16. doi:10.1016/j.jaac.2024.03.016

8. Tornese G, Di Mase R, Munarin J, et al. "Use of gonadotropin-releasing hormone agonists in transgender and gender-diverse youth: a systematic review." Front Endocrinol. 2025;16:1555186. doi:10.3389/fendo.2025.1555186

9. Nos AL, Klein DA, Adirim TA, et al. "Association of gonadotropin-releasing hormone analogue use with subsequent use of gender-affirming hormones among transgender adolescents." JAMA Netw Open. 2022;5(11):e2239758. doi:10.1001/jamanetworkopen.2022.39758

10. Skeith L, Bates SM. "Sex hormone influences on venous thrombotic and cardiovascular risk." N Engl J Med. 2026;394(15):1514–1528. doi:10.1056/NEJMra2202438

11. van Zijverden LM, Thijs A, van Diemen JJK, Wiepjes CM, den Heijer M. "Transgender persons receiving gender-affirming hormone therapy: risk of acute cardiovascular events in a Dutch cohort study." Eur Heart J. 2026;47(21):2660–2669; online 2025. doi:10.1093/eurheartj/ehaf837

12. Glintborg D, Christensen LL, Andersen MS. "Transgender healthcare: metabolic outcomes and cardiovascular risk." Diabetologia. 2024;67(11):2393–2403. doi:10.1007/s00125-024-06212-6

13. Rosendale N, Goldman S, Ortiz GM, Haber LA. "Acute clinical care for transgender patients: a review." JAMA Intern Med. 2018;178(11):1535–1543. doi:10.1001/jamainternmed.2018.4179

14. Leone AG, Trapani D, Schabath MB, et al. "Cancer in transgender and gender-diverse persons: a review." JAMA Oncol. 2023;9(4):556–563. doi:10.1001/jamaoncol.2022.7173

15. National Comprehensive Cancer Network. NCCN clinical practice guidelines: genetic / familial high-risk assessment — breast, ovarian, pancreatic, and prostate. Updated 2026-02-19.

16. National Comprehensive Cancer Network. NCCN clinical practice guidelines: prostate cancer early detection. Updated 2026-02-18.

17. Leone AG, Casolino R, Trapani D, et al. "Position paper of the Italian Association of Medical Oncology on health disparities among transgender and gender-diverse people: the Assisi Recommendations." EClinicalMedicine. 2023;65:102277. doi:10.1016/j.eclinm.2023.102277

18. De Roo C, Schneider F, Stolk THR, et al. "Fertility in transgender and gender-diverse people: systematic review of the effects of gender-affirming hormones on reproductive organs and fertility." Hum Reprod Update. 2025;31(3):183–217. doi:10.1093/humupd/dmae036

19. Ainsworth AJ, Allyse M, Khan Z. "Fertility preservation for transgender individuals: a review." Mayo Clin Proc. 2020;95(4):784–792. doi:10.1016/j.mayocp.2019.10.040

20. Schwartz AR, Moravek MB. "Reproductive potential and fertility preservation in transgender and nonbinary individuals." Curr Opin Obstet Gynecol. 2021;33(4):327–334. doi:10.1097/GCO.0000000000000729

21. Trum HW, Hoebeke P, Gooren LJ. "Sex reassignment of transsexual people from a gynecologist's and urologist's perspective." Acta Obstet Gynecol Scand. 2015;94(6):563–567. doi:10.1111/aogs.12618

22. da Silva LMB, Freire SND, Moretti E, Barbosa L. "Pelvic floor dysfunction in transgender men on gender-affirming hormone therapy: a descriptive cross-sectional study." Int Urogynecol J. 2024;35(5):1077–1084. doi:10.1007/s00192-024-05779-3

23. Horberg M, Thompson M, Agwu A, et al. "Primary care guidance for providers of care for persons with HIV: 2024 update by the HIV Medicine Association of the Infectious Diseases Society of America." Clin Infect Dis. 2024;ciae479. doi:10.1093/cid/ciae479

24. T'Sjoen G, Arcelus J, Gooren L, Klink DT, Tangpricha V. "Endocrinology of transgender medicine." Endocr Rev. 2019;40(1):97–117. doi:10.1210/er.2018-00011

25. Irwig MS. "Testosterone therapy for transgender men." Lancet Diabetes Endocrinol. 2017;5(4):301–311. doi:10.1016/S2213-8587(16)00036-X

26. Coleman E, Radix AE, Bouman WP, et al. Standards of Care for the Health of Transgender and Gender Diverse People, Version 8. 2022. Full guideline. doi:10.1080/26895269.2022.2100644.

27. AVEED US prescribing information. DailyMed.

28. EMA. Restrictions in use of cyproterone due to meningioma risk. 2020. Safety communication.

29. ACR. Transgender Breast Cancer Screening. Appropriateness Criteria.

30. Herndon J, Gupta N, Davidge-Pitts C, et al. "Genital surgery outcomes using an individualized algorithm for hormone management in transfeminine individuals." J Clin Endocrinol Metab. 2024;109(11):2774–2783. doi:10.1210/clinem/dgae269

31. Bhasin S, Brito JP, Cunningham GR, et al. "Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline." J Clin Endocrinol Metab. 2018;103(5):1715–1744. doi:10.1210/jc.2018-00229

32. Winston-McPherson GN, Thomas TA, Krasowski MD, et al. "Estradiol Concentrations for Adequate Gender-Affirming Feminizing Therapy: A Systematic Review." LGBT Health. 2025;12(7):477–489. doi:10.1089/lgbt.2024.0407

33. Jiang DD, Swenson E, Mason M, et al. "Effects of Estrogen on Spermatogenesis in Transgender Women." Urology. 2019;132:117–122. doi:10.1016/j.urology.2019.06.034

34. Gooren L, Morgentaler A. "Prostate Cancer Incidence in Orchidectomised Male-to-Female Transsexual Persons Treated with Oestrogens." Andrologia. 2014;46(10):1156–1160. doi:10.1111/and.12208

35. Deebel NA, Morin JP, Autorino R, Vince R, Grob B, Hampton LJ. "Prostate Cancer in Transgender Women: Incidence, Etiopathogenesis, and Management Challenges." Urology. 2017;110:166–171. doi:10.1016/j.urology.2017.08.032

36. Joint R, Chen ZE, Cameron S. "Breast and Reproductive Cancers in the Transgender Population: A Systematic Review." BJOG. 2018;125(12):1505–1512. doi:10.1111/1471-0528.15258

37. Hartley RL, Stone JP, Temple-Oberle C. "Breast Cancer in Transgender Patients: A Systematic Review. Part 1: Male to Female." Eur J Surg Oncol. 2018;44(10):1455–1462. doi:10.1016/j.ejso.2018.06.035

38. Robertson BD, Lerner BS, Collen JF, Smith PR. "The Effects of Transgender Hormone Therapy on Sleep and Breathing: A Case Series." J Clin Sleep Med. 2019;15(10):1529–1533. doi:10.5664/jcsm.7992

39. Adeleye AJ, Reid G, Kao CN, Mok-Lin E, Smith JF. "Semen Parameters Among Transgender Women With a History of Hormonal Treatment." Urology. 2019;124:136–141. doi:10.1016/j.urology.2018.10.005

40. Iwamoto SJ, Rothman MS, T’Sjoen G, Defreyne J. "Approach to the Patient: Hormonal Therapy in Transgender Adults With Complex Medical Histories." J Clin Endocrinol Metab. 2024;109(2):592–602. doi:10.1210/clinem/dgad536.

41. Misakian AL, Kelley CE, Sullivan EA, et al. "Injectable Estradiol Use in Transgender and Gender-Diverse Individuals throughout the United States." J Clin Endocrinol Metab. 2025;110(9):e2898–e2907. doi:10.1210/clinem/dgaf015.

42. Endo USA. TESTOPEL (testosterone pellets) prescribing information. Revised July 2025. DailyMed.

43. Cheng K, Skolnick A. "Testosterone pellet use in transgender men." Transgend Health. 2023;8(6):494–499. doi:10.1089/trgh.2021.0205.

44. Weyers S, De Sutter P, Hoebeke S, et al. "Gynaecological aspects of the treatment and follow-up of transsexual men and women." Facts Views Vis Obgyn. 2010;2(1):35–54. PMID:25206965.

45. Nik-Ahd F, De Hoedt AM, Butler C, et al. "Prostate-Specific Antigen Values in Transgender Women Receiving Estrogen." JAMA. 2024;332(4):335–337. doi:10.1001/jama.2024.9997

46. US Preventive Services Task Force. "Testicular Cancer: Screening." 2011. Recommendation.

47. Cooney EE, Yeh PT, Kennedy KS, Kaptchuk RP, Wong B, Kennedy CE. "Provision of gender-affirming hormones for trans and gender-diverse adults: a systematic review of health and quality of life outcomes, values and preferences, and costs." EClinicalMedicine. 2025;88:103460. doi:10.1016/j.eclinm.2025.103460

48. Nolan BJ, Zwickl S, Locke P, Zajac JD, Cheung AS. "Early access to testosterone therapy in transgender and gender-diverse adults seeking masculinization: a randomized clinical trial." JAMA Netw Open. 2023;6(9):e2331919. doi:10.1001/jamanetworkopen.2023.31919

49. Tienforti D, Marinelli L, Terrana G, et al. "Bone accrual during puberty suppression and gender-affirming therapy in transgender adolescents: a systematic review and meta-analysis." JAMA Pediatr. 2026;180(10):1094–1104. doi:10.1001/jamapediatrics.2026.2470

50. van de Grift TC, van Gelder ZJ, Mullender MG, Steensma TD, de Vries ALC, Bouman MB. "Timing of puberty suppression and surgical options for transgender youth." Pediatrics. 2020;146(5):e20193653. doi:10.1542/peds.2019-3653

51. Majumder A, Chatterjee S, Maji D, et al. "IDEA Group consensus statement on medical management of adult gender incongruent individuals seeking gender affirmation as male." Indian J Endocrinol Metab. 2023;27(1):3–16. doi:10.4103/ijem.ijem_410_22

52. de Blok CJM, Wiepjes CM, Nota NM, et al. "Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands." BMJ. 2019;365:l1652. doi:10.1136/bmj.l1652

53. Smith J, Ross S, Nambiar K, et al. "BASHH best practice statement on the management of testosterone-associated vulvovaginitis." Int J STD AIDS. 2026;37(9):984–994. doi:10.1177/09564624261458272

54. Blasdel G, Borah L, Navarrete R, Howland R, Kuzon WM Jr, Montgomery JS. "Prostatectomy after gender-affirming vaginoplasty for a transgender woman with prostate cancer." Urol Case Rep. 2024;56:102819. doi:10.1016/j.eucr.2024.102819

55. Baraban E, Ding CKC, White M, et al. "Prostate cancer in male-to-female transgender individuals: histopathologic findings and association with gender-affirming hormonal therapy." Am J Surg Pathol. 2022;46(12):1650–1658. doi:10.1097/PAS.0000000000001964

56. Goldstein Z, Martinson T, Ramachandran S, et al. "Improved rates of cervical cancer screening among transmasculine patients through self-collected swabs for high-risk human papillomavirus DNA testing." Transgend Health. 2020;5(1):10–17. doi:10.1089/trgh.2019.0019

57. Wentzensen N, Massad LS, Clarke MA, et al. "Self-collected vaginal specimens for HPV testing: recommendations from the Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee." J Low Genit Tract Dis. 2025;29(2):144–152. doi:10.1097/LGT.0000000000000885

58. Ding C, Khondker A, Goldenberg MG, et al. "Urinary complications after penile inversion vaginoplasty in transgender women: systematic review and meta-analysis." Can Urol Assoc J. 2023;17(4):121–128. doi:10.5489/cuaj.8108

59. Lo Re M, Pezzoli M, Cocci A, et al. "Urological issues in masculinising genital surgery: a Delphi consensus study." BJU Int. 2026;online ahead of print. doi:10.1111/bju.70428

60. de Nie I, Wiepjes CM, de Blok CJM, et al. "Incidence of testicular cancer in trans women using gender-affirming hormonal treatment: a nationwide cohort study." BJU Int. 2022;129(4):491–497. doi:10.1111/bju.15575