Gender-affirming hormone treatment modulates cancer risk for specific malignancies in transgender individuals, but insufficient data exists for precise risk estimates, leaving screening recommendations broad and cancer management guidance largely extrapolated from cisgender populations.
Key Findings
Results
Transgender women (male sex assigned at birth) on GAHT have an increased risk of breast cancer compared to cisgender men, but a lower risk compared to cisgender women.
A large Dutch cohort study found the standardized incidence ratio (SIR) for breast cancer in transgender women was 46.7 (95% CI 27.2-74.9) compared to cisgender men.
The SIR for breast cancer in transgender women was 0.3 (95% CI 0.2-0.5) compared to cisgender women.
Risk appears to increase with duration of GAHT exposure.
The absolute risk remains low given the low baseline incidence in cisgender men.
Results
Transgender men (female sex assigned at birth) on GAHT do not appear to have a significantly elevated risk of breast cancer compared to cisgender women.
Studies suggest breast cancer risk in transgender men may be lower than in cisgender women, potentially due to mastectomy and the effects of testosterone.
However, residual breast tissue remains after chest masculinization surgery, meaning risk is not eliminated.
Data on long-term outcomes in transgender men are limited, making precise estimates difficult.
Current evidence does not support routine additional breast cancer screening beyond standard recommendations for this group.
Results
Prostate cancer risk in transgender women appears to be lower than in cisgender men, but cases have been reported despite androgen deprivation via GAHT.
Estrogen therapy and androgen deprivation reduce prostate cancer risk in transgender women relative to cisgender men.
Prostate cancer has been reported in transgender women, including cases of aggressive disease, indicating the prostate gland is not fully protected.
PSA levels are suppressed by GAHT, making PSA-based screening less reliable in this population.
Standard PSA thresholds used in cisgender men are not directly applicable; lower thresholds may be needed for screening in transgender women.
Results
Meningiomas are associated with prolonged use of high-dose progestogens, particularly cyproterone acetate, which is used as part of GAHT in transgender women.
Cyproterone acetate (CPA) has been linked to meningioma development, with risk increasing with cumulative dose and duration of use.
A French pharmacovigilance study identified a significantly elevated risk of meningioma with CPA use, with relative risk estimates exceeding 20 in high cumulative dose groups.
Regulatory agencies in several countries have issued warnings about CPA and meningioma risk.
Guidance recommends baseline and periodic MRI surveillance for individuals on long-term high-dose CPA, and consideration of alternative anti-androgens.
Results
Cervical cancer screening recommendations for transgender men are complicated by lower uptake and anatomical or psychological barriers to participation.
Transgender men with a cervix remain at risk of cervical cancer and should continue HPV-based cervical screening per national guidelines.
Studies report significantly lower rates of cervical cancer screening uptake among transgender men compared to cisgender women.
Testosterone-induced atrophic changes to cervical tissue can lead to unsatisfactory smear results, complicating screening interpretation.
Healthcare providers are encouraged to use affirming language and offer supportive accommodations to improve screening participation.
Discussion
Management of active or historical cancers in transgender individuals requires individualized decision-making balancing oncological risk against the significant benefits of GAHT.
There is very limited evidence specifically addressing cancer treatment in transgender individuals, requiring extrapolation from cisgender populations.
Hormone-sensitive cancers (e.g., breast, prostate) present particular complexity regarding continuation or cessation of GAHT during treatment.
The paper emphasizes that 'the significant benefits of GAHT in the face of any hormonal risk' must be weighed carefully.
Multidisciplinary team involvement and shared decision-making with the patient are highlighted as essential components of care.
Abrupt cessation of GAHT can cause significant psychological harm, and this must be factored into oncological management planning.
Discussion
Current cancer screening recommendations for transgender individuals remain broad due to insufficient data for precise risk stratification by age, duration of GAHT, and inherited cancer risk.
The paper states there is 'insufficient data to make precise risk estimates accounting for age and inherited cancer risk.'
Most screening guidelines are extrapolated from cisgender population data and adapted with clinical judgment.
The paper calls for further research to generate transgender-specific evidence to refine screening protocols.
Inherited cancer predisposition syndromes (e.g., BRCA mutations) add additional complexity to risk assessment in transgender individuals.
Berner A, Atkinson S. (2024). The implications of hormone treatment for cancer risk, screening and treatment in transgender individuals.. Best practice & research. Clinical endocrinology & metabolism. https://doi.org/10.1016/j.beem.2024.101909