Eden Openly

Masculinising Hormone Therapy

Evidence Review · ER-007

Identifier: ER-007 · Version: 1.0 · Status: Current · Published: July 2026 · DOI (all versions): 10.5281/zenodo.21268487 · DOI (this version): 10.5281/zenodo.21268488

This is the full review — the complete evidence and every limitation behind it, graded claim by claim. It is the trans-masculine counterpart to the Feminising Hormone Therapy review (ER-005). For the short version, see the companion Evidence Note → (5 min read).

Purpose

To review, and grade the strength of, the evidence for masculinising hormone therapy (testosterone) in adults. This is not a prescribing guide. It should not be used to start, stop, dose-adjust or combine medications without clinical supervision; masculinising hormone therapy should follow local prescribing and monitoring standards. Doses and target ranges are mentioned only where they are needed to explain the evidence.

Two things hold at once, and both belong here: testosterone is an effective, well-established treatment, and its evidence base is thin, largely observational and dependent on comparison with cisgender populations. Three caveats therefore apply to almost every claim below and are stated once so they can be assumed throughout. First, the evidence is overwhelmingly observational — cohorts, cross-sectional studies and case series, with a single small open-label randomised trial — and leans heavily on a few European centres. Second, hard long-term outcomes (cardiovascular events, fractures, cancer, mortality) are largely unmeasured. Third, almost all of it describes standard masculinising doses; nonbinary and low-dose regimens cannot simply be extrapolated.

Executive summary

What this covers. Eight domains: how testosterone works; the virilising changes and their timelines; cardiovascular and metabolic effects; bone health; fertility and reproduction; routes and formulations; mental health and quality of life; and the overall quality of the evidence.

What is reasonably clear. Testosterone produces virilising change in most people with androgen-responsive tissues, predictably in direction though highly variable in degree and speed. Some changes are permanent or partly persistent (voice deepening, clitoral growth, facial/body hair, established scalp-hair loss); others reverse (fat, muscle, menstruation). The best-characterised safety effect is a rise in haematocrit — common, quantifiable and monitorable.[1,6,7]

Where the evidence is weakest. Hard cardiovascular outcomes (heart attack, stroke, clot) are genuinely uncertain in trans men — cohorts detect no consistent clear excess, but that is low-certainty reassurance, not proof of safety. Long-term fracture, cancer and mortality data are essentially absent, as are population-level fertility outcomes.[8,12,13,38]

Where expectations most often go wrong. Testosterone is neither reliable contraception nor a cause of permanent infertility; ovulation can continue even without periods, yet fertility can often recover after stopping. Bone density is maintained largely through aromatisation of testosterone to oestradiol, so oestrogen should not be driven to zero. And “more testosterone” does not mean more virilisation — above-range levels add no known benefit and may add risk.[6,15,22,36]

The honest bottom line. The direction of the major changes is well supported and mechanistically coherent; the long-term, hard-outcome evidence is thin and cisgender-comparison-dependent. This review grades accordingly.

Key take-home messages

  1. Testosterone usually virilises in predictable directions, but the degree and speed vary substantially, and the quoted timelines are clinical-observation estimates, not precise measurements.[1,6]
  2. Some changes are permanent or partly persistent (voice, clitoral growth, facial/body hair, established scalp-hair loss); others are reversible (fat, muscle, menstruation).[1]
  3. The rise in haematocrit is the best-characterised effect; it is formulation- and exposure-associated, not a simple peak-driven phenomenon, and cohorts disagree on which formulation is riskiest.[7,8,9]
  4. Hard cardiovascular outcomes are genuinely uncertain — neither reassurance nor alarm is well supported.[12,13]
  5. Bone density is maintained or slightly improves; aromatised oestradiol appears important for bone, so one should not aim to suppress oestradiol to zero.[15,18]
  6. Testosterone is not contraception, and it does not appear to cause permanent infertility; both myths are wrong.[22,36]
  7. Masculinising therapy shows a consistent, low-certainty signal of improved depression, distress and anxiety — “low certainty” reflects study design, not absent benefit.[32,33,34]

1. How testosterone works (mechanism)

Testosterone acts through three routes, worth separating because they explain both the effects and the monitoring. It acts directly on the androgen receptor (skin, hair follicle, muscle, larynx); after conversion to dihydrotestosterone (DHT) by 5α-reductase, which is more potent at the follicle and skin and contributes substantially to facial/body hair and male-pattern scalp loss; and after aromatisation to oestradiol — not a side issue, because oestradiol derived from testosterone is important for bone (Section 4).

Testosterone also suppresses the hypothalamic–pituitary–ovarian axis, lowering LH and FSH, which suppresses ovarian activity — often, but not always, sufficiently to stop ovulation (Section 5). Mechanism explains plausibility, not magnitude: that a pathway exists does not tell us how large or how consistent the effect will be.

Confidence: 🟢 (mechanism) / 🟡 (magnitudes). The pathways are well established; the size of each downstream effect is more variable.

2. Virilising effects and timelines

Variability is the rule. Testosterone virilises most people with androgen-responsive tissues, but degree and speed differ, and the timelines below are clinical-observation and consensus estimates, not rigorous prospective measurement — the source guideline says so.[1] Age at start interacts with pubertal history, prior puberty suppression, genetics and dose, so “younger equals faster or more complete” is a tendency, not a rule.[6]

Permanence varies. Voice deepening and clitoral growth are typically permanent; facial and body hair are often partly persistent (density may lessen after stopping); established male-pattern scalp loss may be partly irreversible once follicular miniaturisation is set; fat, muscle and menstruation are reversible.[1,6] Onset and maximum figures follow the Endocrine Society clinical-practice-guideline timetable.[1]

Change Onset Maximum If stopped
Cessation of menses 2–6 months — Reversible
Increased libido 1–3 months — Reversible
Skin oiliness / acne 1–6 months 1–2 years Usually improves with dose reduction/stopping; scarring may persist
Fat redistribution 1–6 months 2–5 years Largely reversible
Muscle mass / strength 6–12 months 2–5 years Reversible
Clitoral growth 3–6 months (starts ~3–4 mo) 1–2 years; final length commonly ~4–5 cm Typically permanent
Vaginal / genital atrophy 3–6 months 1–2 years Reversible
Facial & body hair 6–12 months ~4–5 years Often partly persistent
Voice deepening 6–12 months 1–2 years Typically permanent
Scalp hair loss 6–12 months Variable Partly irreversible once established

Two measured findings carry more weight than the consensus timeline. First, amenorrhoea is not the same as anovulation: in a prospective cohort of 31 trans men, at six months 68% reached male-range testosterone and 16% still had menses;[3] and in a surgical-histology sample, 17 of 52 amenorrhoeic transmasculine people on testosterone showed evidence of recent ovulatory activity — a surgical-sample finding that should not be read as a general monthly ovulation rate.[36] Second, above-range testosterone is not known to improve virilisation and may increase adverse-effect risk; targets are ranges, not “more is better.”[6] Acne is graded in the dedicated acne review and is only pointed to here.[5]

Sexual and genitourinary function. Libido commonly increases; genital and vaginal atrophy can cause dryness, discomfort or dyspareunia (relevant to receptive or penetrative sex and to speculum examinations); arousal changes are reported. The data are limited and mostly self-report.[6]

Confidence: 🟡 Moderate. Direction of change is well supported; timelines are consensus estimates and the degree of change is highly variable.

3. Cardiovascular and metabolic effects

This is strongest where numbers exist (red-cell mass) and weakest on lifetime outcomes; the gap is stated rather than smoothed over.

Haematocrit rise — the best-characterised effect. A meta-analysis found haemoglobin rose by about 1.48 g/dL (95% CI 1.17–1.78) and haematocrit by about 4.39 percentage points (3.52–5.26), with erythrocytosis in roughly 11% in the first year; all formulations raise haematocrit, with differences by formulation and threshold.[7] In the largest cohort (n=1,073), erythrocytosis occurred in 11% at a haematocrit above 0.50, 3.7% above 0.52 and 0.5% above 0.54, with the sharpest rise in the first year; risk factors were long-acting intramuscular undecanoate, smoking, higher BMI, older age at start and predisposing pulmonary or haematological history — but higher testosterone level per se was not associated with a haematocrit above 0.50.[8] The ENIGI cohort (n=192) found erythrocytosis in 11.5%, and — importantly — lower on undecanoate than enanthate (9.2% vs 15.9%),[9] which conflicts with the higher odds for long-acting intramuscular preparations in the largest cohort. Against cisgender men, the hazard ratio for erythrocytosis was about 7.4 at the 0.52 threshold.[7]

The honest synthesis. The haematocrit rise is formulation- and exposure-associated and is modified by smoking, BMI, age and pulmonary or haematological history; a simple peak-mediated causal model is not established, and cohorts disagree on which formulation is riskiest. Management is dose reduction or spacing, formulation change, and occasionally phlebotomy; target ranges and intervals belong to the monitoring review.

Lipids and blood pressure. The most consistent change is a fall in HDL cholesterol, with variable LDL and triglyceride effects and modest changes in blood pressure and BMI — surrogate markers, not outcomes.[11]

Hard cardiovascular outcomes. The Amsterdam[12] and STRONG/Kaiser[13] cohorts detect no consistent clear excess of heart attack, stroke or clot in trans men (the stronger signals were in trans women). This is low-certainty reassurance, not proof of safety: event numbers are small, follow-up is short, baseline risks differ, the erythrocytosis-to-thrombosis link is unquantified,[14] and the studies are not powered to exclude risk. Much cardiovascular inference is borrowed from cisgender-men testosterone-deficiency and PCOS/androgen literature.

Confidence: 🟢 (haematocrit effect) / 🔴 (mechanism, and hard cardiovascular outcomes).

4. Bone health

Bone density is maintained or slightly rises in available cohorts. The largest prospective study found total-hip density up about 1% at one year with no meaningful femoral-neck change; long-term follow-up shows maintenance or increase,[15,16] and UCSF summarises trans men on testosterone as generally showing no change or increased density.[6]

Aromatised oestradiol appears important for bone — a contribution, not proof of sole mechanism. The density rise was largest in older or post-menopausal trans men (oestradiol-low at baseline, raised via aromatisation), while younger oestradiol-replete trans men gained little;[15,17] and testosterone plus an aromatase inhibitor is associated with lower bone density than testosterone alone.[18] The actionable point: do not aim to suppress oestradiol to zero (for example with aromatase inhibitors) — a very low oestradiol on testosterone is a warning sign for bone, not a target.

Comparator ambiguity: higher density than cisgender women;[19] possibly lower than cisgender men in a small case-control study.[20] And bone density is not fracture: studies measure density and microarchitecture (surrogates); fracture-outcome data are essentially absent, so long-term fracture risk is unknown either way.

Confidence: 🟡 (density maintained) / 🔴 (fracture outcomes, absent).

5. Fertility and reproduction

Two opposite myths are both wrong: that testosterone is reliable contraception, and that it causes permanent infertility.

Testosterone is not contraception. Anovulation is usual but neither immediate nor reliable — ovulation can occur early, within weeks of starting,[21] and surgical histology shows recent ovulatory activity in a substantial minority (17 of 52) of amenorrhoeic people on testosterone.[36] Pregnancy on testosterone is documented.[22] Testosterone should not be used in pregnancy: it is contraindicated, is teratogenic, and may cause virilisation of a female fetus (regulatory labelling).[40] Anyone for whom pregnancy is possible and unwanted needs a testosterone-compatible contraceptive method — the options belong to the monitoring review.

Fertility can often recover after stopping. In the key survey, 80% resumed menses within six months of stopping, 7% used fertility medication, and obstetric outcomes were broadly similar.[22] Unassisted conception after stopping is documented;[23] oocyte retrieval remains viable after prolonged testosterone, with no clear relationship to the length of prior suspension,[24] and yields and quality comparable to cisgender women.[25] But population-level conception rates and live-birth probabilities remain uncertain — the reassuring data are small cohorts and case series with intermediate outcomes, not population outcomes.

Ovary and endometrium. Polycystic-appearing morphology is common (about 35% in a histopathology systematic review); ovarian histology is benign, and ovarian reserve appears preserved in short-term data (studies to about one year, based on reserve markers rather than fertility outcomes).[24,38] Testosterone does not uniformly induce endometrial atrophy: in hysterectomy series, proliferative or active endometrium is common and persists even with amenorrhoea — about 69% active in one multicentre series (n=94) and about 40% proliferative in another (n=81), unchanged in the amenorrhoeic subgroup.[27] So unexplained or breakthrough bleeding warrants evaluation, and cervical screening still applies on the usual schedule (with atrophy-related sampling caveats) — logistics belong to the monitoring review.

Cancer evidence. A 2024 histopathology systematic review of hysterectomy and oophorectomy specimens (522 endometrial) found predominantly atrophic (~49%) or proliferative (~47%) endometrium, with endometrial intraepithelial neoplasia in about 2.3% and carcinoma in about 0.2%, and no ovarian malignancies among 410 patients.[38] These are surgical-specimen figures from people undergoing gender-affirming or symptomatic surgery — specimen-biased, and not population screening-prevalence or lifetime-risk estimates. They are reassuring against a large excess but do not demonstrate zero risk; long-term endometrial, ovarian and chest-tissue cancer risk on extended testosterone remains an open question.

Confidence: 🟢 (not contraception) / 🟡 (fertility can recover) / 🔴 (long-term conception, offspring and cancer outcomes).

6. Routes, formulations and dosing shape

Several routes are effective; the clinically useful axis is how steady the levels are. Peaks may influence aromatisation and some laboratory effects, but formulation–erythrocytosis relationships are not explained by peaks alone (Section 3).

The link from route to hard outcomes is inferred, not demonstrated; target ranges and monitoring belong to the monitoring review.

Confidence: 🟡 (formulation profiles) / 🔴 (route → hard outcomes).

7. Mental health and quality of life

This is graded down the middle: the signal is reported and its certainty, and both overclaims are named as wrong.

The signal. Starting therapy is associated with reduced depressive symptoms and distress, and in trans-masculine people reduced anxiety. A 2023 review of 46 studies found gender-affirming hormone therapy consistently reduced depressive symptoms and psychological distress, while quality-of-life evidence was inconsistent.[32] A 20-study review agreed on direction, with low-strength evidence.[33] An open-label randomised trial (n=64) found immediate testosterone lowered depression at three months (PHQ-9 mean difference −5.6, 95% CI −6.8 to −4.4).[34]

Why “low certainty” does not mean “no evidence.” Low certainty here reflects open-label design, small samples, short follow-up (three months), selection, subjective outcomes and confounding (surgery, social transition and psychotropics are rarely adjusted for) — not the absence of a benefit signal. So both claims fail: “proven to fix mental health” (no — low-certainty, confounded, and not a treatment for a diagnosis) and “no evidence it helps” (no — a consistent signal plus a randomised trial, graded low by design).[32,33,34]

Masculinising nuances. Mood is less uniform than depression and anxiety (one 12-month cohort found no mood change);[35] greater anger expression (not intensity) is reported, and is noted here neutrally.[32] Suicide-specific and long-term outcomes are not established either way.[33]

This section discusses mental health, including suicide as a topic in the research literature. It is general information, not personal medical advice, and masculinising therapy is not a substitute for appropriate mental-health care where that is needed. (See the support note at the end of this article.)

Confidence: 🟡 (depression/distress/anxiety benefit) / 🔴 (quality of life; suicide-specific and long-term outcomes).

8. Evidence quality

A core aim of this review is to be explicit about how strong the evidence is. The evidence base is overwhelmingly observational — cohorts, cross-sectional studies and case series — plus a single small open-label randomised trial on mental health.[34] High-certainty evidence for long-term clinical endpoints is largely absent, and is hard to obtain for an unblindable intervention, though some mechanistic claims and consistent directional effects (voice deepening, the haematocrit rise) are themselves reasonably firm. The literature leans on a few centres (Amsterdam, Ghent, ENIGI), so the same cohorts recur across topics at the cost of generalisability. Hard endpoints — long-term cardiovascular events, fractures, cancer and mortality — are largely absent, and follow-up is mostly short to medium. Much inference is cisgender-comparison-dependent, drawing on cisgender-men deficiency data and the PCOS/androgen literature. And almost all of it describes standard masculinising doses: nonbinary and low-dose regimens cannot simply be extrapolated, and the evidence for them is thinner still.

Ratings use the same traffic-light scheme as the rest of this series — 🟢 reasonably robust, 🟡 moderate, 🔴 limited — judging the type of evidence, its consistency, how directly it applies to trans men, and the size of the effect against its uncertainty. These are editorial judgements, not formal GRADE ratings. For more on how we weigh evidence in this field, see Reading the Evidence.

Topic Confidence Why
Virilisation occurs, predictable in direction 🟢 Robust Consistent across cohorts and clinical experience; degree varies.[1,6]
Virilisation timelines (onset/maximum) 🟡 Moderate Consensus/clinical-observation tables, not rigorous prospective measurement.[1]
Haematocrit rise (effect) 🟢 Robust Meta-analysis + large cohorts; consistent and quantified.[7,8]
Haematocrit — peak-driven mechanism 🔴 Low Formulation-/exposure-associated; cohorts disagree; not explained by peaks.[8,9]
Lipids (HDL fall) 🟡 Moderate Consistent direction; surrogate marker, not outcome.[11]
Hard cardiovascular outcomes 🔴 Low No consistent excess detected, but underpowered to exclude; confounded.[12,13]
Bone density maintained/increased 🟡 Moderate Prospective cohort data; oestradiol contribution supported.[15,17]
Fracture outcomes 🔴 Low Essentially absent; density is a surrogate.
Testosterone is not contraception 🟢 Robust Ovulation documented despite amenorrhoea; pregnancy on testosterone reported.[22,36]
Fertility recovery after stopping 🟡 Moderate Menses resume, conception documented; population odds uncertain.[22,24]
Endometrial/ovarian cancer risk 🔴 Low Surgical-specimen data only; specimen-biased, not population risk.[38]
Mental-health benefit (depression/distress) 🟡 Moderate 46-study review + open-label RCT; consistent signal, graded low by design.[32,34]
Nonbinary / low-dose regimens 🔴 Low Standard-dose cohorts do not extrapolate; evidence thin.[39]

9. Frequently asked questions

Is testosterone contraception? No — ovulation can continue even with no periods, and pregnancy is possible. (Section 5)

Will voice changes reverse if I stop? No — voice deepening is typically permanent. (Section 2)

Does masculinising mean driving oestrogen as low as possible? No — oestradiol protects bone; do not aim to suppress it to zero. (Section 4)

Does testosterone make you permanently infertile? Not supported — fertility can often recover, though long-term odds are uncertain. (Section 5)

Does “no periods” mean bleeding is nothing to worry about? No — proliferative endometrium can occur even with amenorrhoea; unexplained bleeding needs review. (Section 5)

Is the mental-health benefit proven, or is there no evidence? Neither — it is a consistent, low-certainty signal. (Section 7)

Does higher testosterone work better or faster? No — above-range levels add no known virilisation and may raise adverse-effect risk. (Sections 2, 3, 6)

10. Clinical bottom line

  1. Testosterone usually virilises in predictable directions but variably in degree and speed; permanence differs, so consent should distinguish reversible from permanent or partly-persistent change.[1,6]
  2. Haematocrit is the key monitorable signal — formulation- and risk-factor-associated, not a simple peak story.[7,8]
  3. Hard cardiovascular outcomes are uncertain — neither reassurance nor alarm is well supported.[12,13]
  4. Do not aim to suppress oestradiol to zero — it protects bone.[15,18]
  5. Testosterone is not contraception, and it does not appear to end fertility — discuss preservation before starting, and treat unexplained bleeding as warranting work-up; cervical screening still applies.[22,36]
  6. Masculinising therapy shows a consistent, low-certainty mental-health benefit — describe it as exactly that.[32,34]

Sidebar — Virilising changes at a glance

Change Onset Permanence Evidence
Cessation of menses 2–6 months Reversible 🟡
Skin oiliness / acne 1–6 months Reversible (scarring may persist) 🟡
Fat redistribution 1–6 months Reversible 🟡
Muscle mass / strength 6–12 months Reversible 🟡
Clitoral growth 3–6 months Permanent 🟡
Facial / body hair 6–12 months Often partly persistent 🟡
Voice deepening 6–12 months Permanent 🟡
Scalp hair loss 6–12 months Partly irreversible 🟡

Sidebar — Common myths

Myth Evidence Strength
“Testosterone is contraception.” Ovulation can continue despite amenorrhoea; pregnancy on testosterone is documented.[22,36] 🟢
“Testosterone makes you permanently infertile.” Menses resume in most within six months of stopping; conception is documented.[22] 🟡
“Masculinising means driving oestrogen to zero.” Aromatised oestradiol protects bone; suppressing it to zero harms bone.[15,18] 🟡
“Higher testosterone gives more virilisation.” Above-range levels add no known virilisation and may raise adverse-effect risk.[6] 🟡
“No periods means no bleeding to worry about.” Proliferative endometrium can persist despite amenorrhoea; unexplained bleeding needs review.[27] 🟡

Evidence appendix — the key studies at a glance

Design and applicability for the main sources behind this review, so each claim can be weighed directly.

Study Design Population (n) Outcome measured Applies to trans men? Key limitation
Hembree / Endocrine Society 2017[1] Clinical practice guideline — Virilisation timeline (Table 13) Directly (consensus) Clinical-observation estimates, not measured
Deutsch 2015[3] Prospective cohort 31 trans men Testosterone level, menses Directly Small; short follow-up
Okano 2025[7] Systematic review/meta-analysis Multiple cohorts Haemoglobin / haematocrit Directly Formulation heterogeneity
Madsen 2021[8] Retrospective cohort 1,073 trans men Erythrocytosis, determinants Directly Observational; single centre
Defreyne / ENIGI 2018[9] Prospective cohort 192 trans men Haematocrit by formulation Directly Conflicts with [8] on formulation
Wiepjes 2017[15] Prospective cohort Multicentre Bone mineral density (1 year) Directly Surrogate; no fracture data
Light 2014[22] Survey Trans men with pregnancy Menses resumption, pregnancy Directly Self-report; selected sample
Grimstad 2019 / Hawkins 2021[27] Retrospective case series 94 / 81 Endometrial histology Directly Surgical specimens; selected
Nolan 2023[34] Open-label RCT 64 Depression (PHQ-9), dysphoria Directly Open-label; 3 months; small
Asseler 2024[36] Surgical histology 52 amenorrhoeic Recent ovulatory activity Directly Not a monthly ovulation rate
Histopathology SR 2024[38] Systematic review 522 endometrial / 410 ovarian Endometrial/ovarian pathology Directly Specimen-biased; not population risk

What would settle the open questions: prospective cohorts with hard endpoints (cardiovascular events, fractures, cancer, mortality), population-level fertility outcomes, and studies designed for nonbinary and low-dose regimens.

What we know / What we don’t know

What we know

What we don’t know

Related Eden Openly reviews

A note on support

This article is health information, not personal medical advice, and it is not a substitute for assessment by a qualified clinician. It should not be used to start, stop, dose-adjust, change the route of, or combine medications without clinical supervision, and masculinising hormone therapy should follow local prescribing and monitoring standards. New or changing symptoms — including unexplained bleeding — are worth discussing with your own clinician. If you are struggling with your mental health, you are not alone and support is available; please reach out to your clinician or a local support line, and in an emergency contact your local emergency services.

Revision history

Version 1.0 — July 2026. First published.

References

Population flags mark sources whose primary evidence is from cisgender populations and is extrapolated to trans men.

  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. (Masculinising timetable = Table 13.)
  2. Dimakopoulou A, Seal LJ. Testosterone and other treatments for transgender males and non-binary trans masculine individuals. Best Pract Res Clin Endocrinol Metab. 2024. (Clitoral growth onset ~3–4 months, complete by ~1 year; final length ~4–5 cm.)
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  4. Endocrine management of adult transgender persons — clinical practice guideline. Indian J Endocrinol Metab. 2025.
  5. Wierckx K, Van de Peer F, Verhaeghe E, et al. Short- and long-term clinical skin effects of testosterone treatment in trans men. J Sex Med. 2014;11(1):222–229. (See companion: Acne in Gender-Affirming Care.)
  6. Deutsch MB, ed. Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People. 2nd ed. University of California, San Francisco (UCSF Gender Affirming Health Program); 2016.
  7. Okano SHP, Braga GC, Cantelli DAL, et al. Effect of testosterone formulations on haematocrit in transgender individuals: a systematic review. Andrology. 2025;13(3):422–430. doi:10.1111/andr.13695. (Hb +1.48; Hct +4.39 pp; ~11% first year; carries the STRONG-cohort hazard ratio 7.4 vs cisgender men.)
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  19. Cheung AS, et al. Higher total volumetric bone mineral density in trans men than cisgender women. [Comparator: cisgender women.]
  20. Case-control study (n=19 vs 19, BMI/age-matched): lower total-body and femoral-neck bone density in trans men versus cisgender men. Steroids 2021. [Comparator: cisgender men.]
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  25. Oocyte-outcome series (Boston IVF; Israeli cohort): yields and quality comparable to cisgender women after long-term testosterone.
  26. Fertility preservation in a transgender man without prolonged discontinuation of testosterone (case report; letrozole protocol). PMC8244337.
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  28. Pharmacokinetics of intramuscular versus subcutaneous testosterone in gender-affirming therapy (peak–trough variation).
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  35. Impact of gender-affirming interventions on mental health and body image: a systematic review (16 studies, 2024). (12-month no-mood-change finding in transmasculine participants.)
  36. Asseler JD, et al. Recent ovulatory activity on histology in amenorrhoeic transmasculine people on testosterone (17 of 52; surgical sample, not a monthly rate). Cell Rep Med. 2024. PMID 38402622.
  37. Sexual and genitourinary function on testosterone (libido, atrophy, dyspareunia, arousal) — UCSF masculinising overview [6] and cohort reports.
  38. Uterine and Ovarian Histopathology After Testosterone for Gender Affirmation: A Systematic Review. 2024. PMID 39385954. (522 endometrial specimens: ~49% atrophic, ~47% proliferative, 3% secretory; endometrial intraepithelial neoplasia ~2.3%, carcinoma ~0.2%; 410 ovarian: ~35% polycystic-appearing, no malignancy — surgical-specimen, not population screening.)
  39. Nonbinary and low-dose testosterone — limited evidence; standard-dose cohort data are not directly extrapolable.
  40. US FDA prescribing information — Depo-Testosterone (testosterone cypionate injection, USP), Contraindications/Warnings (Pregnancy): “The use of testosterone in women who are pregnant is contraindicated. Testosterone is teratogenic and may cause fetal harm… virilization of the female fetus.” accessdata.fda.gov/drugsatfda_docs/label/2018/085635s040lbl.pdf.