Estrogen Preparations

Oestrogen preparations replace or supplement oestrogen. They treat menopausal vasomotor symptoms and genitourinary symptoms, prevent bone loss, replace oestrogen in premature ovarian insufficiency, Turner syndrome and hypogonadism, and are part of combined contraceptives. Benefit depends on starting early and choosing a low-risk route, and the endometrium needs progestogen protection when the uterus is present.

Mechanism. Oestradiol binds oestrogen receptors alpha and beta in the brain, bone, vagina, endothelium and endometrium. It stabilises thermoregulation, maintains bone formation, thickens vaginal epithelium and stimulates endometrial growth.

Pharmacokinetics. Oral oestradiol is metabolised in the gut and liver, so oestrone is high and clotting factors increase. Transdermal and vaginal routes avoid first-pass metabolism. Conjugated equine oestrogens contain several oestrogens, and ethinylestradiol is a potent synthetic used in contraception.

Progestogen cover. For women with a uterus give a progestogen: micronised progesterone 100 mg daily or 200 mg for 12 to 14 days of each month, medroxyprogesterone acetate, norethisterone, or a levonorgestrel intrauterine system. Women without a uterus need oestrogen alone.

Dose in specific conditions.

• Premature ovarian insufficiency and Turner syndrome: oestradiol doses higher than menopausal doses, continued to about 51 years; children start low (for example, 0.25 mg or 3 micrograms/kg) to induce puberty.
• Vasomotor symptoms: lowest effective dose; review yearly.

• First-line. Moderate to severe vasomotor symptoms in women under 60 or within 10 years of menopause; local vaginal oestrogen for genitourinary syndrome; replacement in premature ovarian insufficiency.
• Alternative. Non-hormonal drugs for hot flushes (venlafaxine, gabapentin, fezolinetant); tibolone; vaginal moisturisers.
• Specialist. Osteoporosis prevention in women under 60 when other treatments are unsuitable; hypogonadism; delayed puberty; gender-affirming care.
• Emergency. Conjugated oestrogens 25 mg intravenously every 4 to 6 hours for acute heavy uterine bleeding (specialist, now seldom used).

Selection. Offer oestrogen after a discussion of risks and benefits. Prefer transdermal oestradiol with micronised progesterone for lowest thrombosis and breast risk. Use local oestrogen alone for genitourinary symptoms regardless of age.

Contraindications. Breast cancer (current or past); oestrogen-sensitive cancer; undiagnosed vaginal bleeding; active or past venous thromboembolism or arterial disease (myocardial infarction, stroke); active liver disease; porphyria; pregnancy; untreated endometrial hyperplasia.

Serious adverse effects.

• Venous thromboembolism (oral route higher), stroke, gallbladder disease.
• Breast cancer risk with combined therapy over about 5 years; endometrial cancer if oestrogen is used alone with a uterus.
• Breast tenderness, nausea, headache, bloating, breakthrough bleeding.
• Hypertriglyceridaemia and rare liver tumours.

Major interactions. Enzyme inducers (rifampicin, carbamazepine, phenytoin, St John’s wort) lower levels; levothyroxine dose may need to rise with oral oestrogen; tamoxifen opposes oestrogen effects; some antiretrovirals change levels.

Common prescribing errors.

• Oestrogen alone in a woman with a uterus.
• Starting after many years of menopause without review.
• Using oral oestrogen in high thrombosis risk.
• Treating unexplained bleeding with hormones before investigation.
• Forgetting to review the need each year.

Special groups.

• Pregnancy: not used.
• Breastfeeding: avoid high doses; may reduce milk.
• Children: induction of puberty is specialist care.
• Older adults: avoid starting systemic therapy after age 60 or 10 years from menopause; vaginal oestrogen remains safe.
• Kidney: caution with fluid retention.
• Liver: avoid in active disease.
• East Africa: menopause care is often missed; patches and gels may be costly or unavailable, while oral oestradiol is cheaper; check for hypertension, smoking and sickle cell disease before choosing; evaluate abnormal bleeding for cervical and endometrial disease.

Monitoring. Symptom review at 3 months, then yearly; blood pressure; breast screening under the national programme; bleeding pattern; weight.

Referral and escalation. Unscheduled bleeding after the first 6 months; breast lump; leg swelling or chest pain; visual disturbance; severe headache.

Comparison with alternative classes. Oestrogen is the most effective treatment for hot flushes and genitourinary symptoms, but carries thrombosis and cancer risk; non-hormonal drugs are weaker but safer for women with contraindications.