Side Effects of Hormone Therapy

Q: How dangerous is hormone therapy?

With proper medical supervision, most risks can be managed, but they are not zero. Thrombosis, cardiovascular effects and potentially increased risks of cancer and mortality are real. Long-term safety has not been fully mapped out. Annual monitoring with blood tests and blood pressure measurement is the minimum. This monitoring is absent with self-medication, and the risks are substantially higher.

Q: Does estrogen increase the risk of breast cancer?

It may with long-term use, comparable to postmenopausal hormone therapy (HRT). Adequate screening therefore remains necessary, in accordance with the guidelines that apply to the relevant sex, such as mammography. Annual monitoring is the minimum. Those who use hormones without medical supervision miss this monitoring and face substantially higher risks.

Q: What is erythrocytosis?

An excessively high concentration of red blood cells, which makes the blood more viscous and increases the risk of thrombosis. It requires regular monitoring when using testosterone. Hematocrit, the proportion of red blood cells in the blood, is therefore measured during the annual blood test. Without this monitoring, the risk of thrombosis increases considerably.

Q: Can I stop hormone therapy?

Yes, but stopping has consequences: partial return of original characteristics, a risk of bone loss without gonads, and severe psychological problems in some people. A medically supervised tapering process is essential. Hormone therapy is a lifelong pharmacological alteration of a healthy hormonal system, so stopping also has medical consequences.

Q: Is cyproterone acetate safe?

Not without qualification. The drug is associated with meningioma, a benign brain tumor, when used long term and at higher doses. The EMA has issued a warning about this and advises lower doses, shorter courses and careful assessment of the indication. Regular monitoring is part of its use. This monitoring is absent with self-medication.

Rack of blood tubes with purple and red caps in a laboratory. — Photo: Tahir Xəlfəquliyev via Pexels

Hormone therapy for transgender people is not a replacement for a deficiency, but a lifelong pharmacological alteration of a healthy hormonal system. This entails substantial side effects and risks, some well documented and others insufficiently studied. Informed decision-making requires a complete description of what we know — and what we do not.

Side effects of estrogen therapy

Thrombosis and pulmonary embolism: increased risk of thrombosis, particularly with oral administration; also increased by smoking, obesity or clotting disorders.
Cardiovascular effects: changes in blood pressure and lipid levels; recent cohort studies show increased cardiovascular morbidity and mortality among trans women over the longer term. See cardiovascular disease during transition.
Liver strain: particularly with oral administration (first-pass effect).
Breast cancer: long-term use may increase the risk, comparable to postmenopausal HRT (Asscheman et al.; De Blok et al. 2019).
Prolactinoma: hyperprolactinemia and, in rare cases, prolactinoma (a pituitary tumor).
Mood: mood swings, depression or, conversely, improvement — highly individual.
Bone density: after orchiectomy without adequate estrogen replacement, there is a risk of osteoporosis. See bone density during transition.

Side effects of anti-androgens

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

Side effects of testosterone therapy

Erythrocytosis: an excessively high hematocrit, which significantly increases the risk of thrombosis and requires monitoring.
Cardiovascular effects: an unfavorable shift in the lipid profile (HDL decreases, LDL increases). The long-term consequences for trans men have not been sufficiently studied.
Acne and skin problems: common, sometimes severe.
Androgenic hair loss: accelerated in those with a genetic predisposition.
Vaginal atrophy: with long-term use, the mucous membrane becomes thinner, drier and more vulnerable, causing symptoms and potentially increasing the risk of infection.
Liver: strain with some forms of administration.
Sleep and aggression patterns: irritability and poorer sleep can occur, particularly after injections.
Effects on the uterus and ovaries: insufficient long-term data on carcinogenic risk with chronic testosterone exposure.

Cancer risks

Long-term studies into cancer risks associated with hormone therapy are limited and largely based on small, early cohorts. Points of concern include breast cancer in trans women (potentially increased risk), the prostate (testosterone suppression is protective, but not absolutely), and endometrial and ovarian carcinoma in trans men who retain their uterus and ovaries. The Cass Review (2024) highlights the systematic lack of adequate long-term monitoring.

What we do not know enough about

Important gaps in knowledge include:

Cardiovascular morbidity and mortality after 20 or more years of hormone therapy.
Cancer incidence in all tissues (breast, prostate, uterus, liver).
Effects on cognitive aging.
Bone health after stopping treatment without gonads.
Psychological well-being among detransitioners who stop taking hormones after long-term use — an overlooked group.

Importance of monitoring

Annual monitoring is the minimum: blood tests (hematocrit, liver function, lipid levels, hormone levels, prolactin), blood pressure, cardiovascular risk assessment, and cancer screening (mammography, prostate screening) in accordance with the corresponding sex-based guidelines. This monitoring is absent with self-medication, and the risks are substantially higher. A description of the physical side effects of hormonal transition can be found at genderzorgen.nl.

How dangerous is hormone therapy?

Does estrogen increase the risk of breast cancer?

What is erythrocytosis?

Can I stop hormone therapy?

Is cyproterone acetate safe?