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Side effects of hormone therapy

Hormone therapy in transgender people is not a top-up for a deficiency, but a lifelong pharmacological switching of a healthy hormone system. With that come substantial side effects and risks, some well documented, some insufficiently researched. Informed decision-making requires a full description of what we know — and what we do not.

Side effects of oestrogen therapy

• Thrombosis and pulmonary embolism: elevated risk, particularly with oral administration; also elevated in smokers, overweight or clotting disorders.
• Cardiovascular effects: changes in blood pressure and lipids; recent cohort studies show elevated cardiovascular morbidity and mortality in trans women over the long term.
• Liver burden: particularly with oral administration (first-pass effect).
• Breast cancer: with long-term use possibly elevated risk, comparable to post-menopausal HRT (Asscheman et al.; De Blok et al. 2019).
• Prolactinoma: hyperprolactinaemia and in rare cases a prolactinoma (pituitary tumour).
• Mood: mood swings, depression, or improvement — highly individual.
• Bone density: after orchidectomy, without adequate oestrogen substitution, risk of osteoporosis.

Side effects of anti-androgens

• Cyproterone acetate: with long-term use and higher doses associated with meningioma (benign brain tumour). The EMA has issued a warning on this; lower doses and shorter courses are recommended.
• Bicalutamide: hepatotoxicity; less studied for transgender indications than for prostate cancer.
• Spironolactone: hyperkalaemia, effects on kidney function and blood pressure.
• GnRH analogues (used in adults to suppress testosterone): bone loss, mood effects.

Side effects of testosterone therapy

• Erythrocytosis: high haematocrit; significantly raises thrombosis risk and requires monitoring.
• Cardiovascular: unfavourable shift in lipid profile (HDL falls, LDL rises). Long-term consequences in trans men insufficiently researched.
• Acne and skin problems: the rule, sometimes severe.
• Androgenic hair loss: accelerated with genetic predisposition.
• Vaginal atrophy: with long-term use thinner, drier and more vulnerable mucosa, with complaints and possibly increased infection risk.
• Liver: burden with some routes of administration.
• Sleep and aggression patterns: irritability, worse sleep occurs, particularly after injections.
• Effects on uterus and ovaries: insufficient long-term data on carcinogenic risk with chronic testosterone exposure.

Cancer risks

Long-term studies of cancer risks under hormone therapy are limited and largely based on small, early cohorts. Points of attention: breast cancer in trans women (possibly elevated), prostate (testosterone suppression is protective, but not absolute), and endometrial and ovarian carcinoma in trans men retaining uterus and ovaries. The Cass Review (2024) points to the systematic lack of adequate long-term monitoring.

What we do not know well

Important knowledge gaps:

• Cardiovascular morbidity and mortality after 20+ years of hormone therapy.
• Cancer incidence in all tissues (breast, prostate, uterus, liver).
• Effects on cognitive ageing.
• Bone health on discontinuation without gonads.
• Psychological well-being in detransitioners who stop hormones after long-term use — an under-studied group.

Importance of monitoring

Annual check-up is a minimum: blood tests (haematocrit, liver, lipids, hormone levels, prolactin), blood pressure, cardiovascular risk assessment, cancer screening (mammography, prostate) according to the corresponding sex-based guidelines. Self-medication lacks this and risks are substantially higher.