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Oestrogen Replacement Therapy Pregnancy: Contraindicated — HRT not indicated in pregnancy. If inadvertently given, no clear evidence of harm from transient exposure.

Estradiol (HRT — Hormone Replacement Therapy)

Brand names: Elleste Solo (oral), Evorel (patch), Oestrogel (gel), Lenzetto (spray), Vagifem (vaginal tablet), Estring (vaginal ring)

Adult dose

Dose: Systemic HRT (oral): estradiol 1–2mg OD. Transdermal patch: 25–100 micrograms/24h — apply twice weekly (or weekly for some brands). Gel (Oestrogel): 0.75–1.5mg (1–2 pumps) daily to skin. Vaginal (local): Vagifem 10 microgram tablet: 1 tablet daily for 2 weeks then twice weekly. Estring ring: 1 ring inserted for 90 days.
Route: Oral / Transdermal patch / Gel / Vaginal
Frequency: Daily (oral/gel) or twice weekly/weekly (patches); twice weekly (vaginal tablets)
Max: 2mg OD oral; 100 micrograms/24h transdermal; individualised for gel
Women with intact uterus MUST have progestogen added (cyclical or continuous combined HRT) to prevent endometrial hyperplasia. Transdermal route preferred in women with VTE risk, hypertriglyceridaemia, or migraine — avoids hepatic first-pass, does not increase clotting factors. Vaginal preparations (Vagifem, Estring): local effect only — minimal systemic absorption; progestogen not required.

Paediatric dose

Route: Oral / Transdermal
Frequency: Daily
Max: Individualised
Used in adolescents with primary ovarian insufficiency (Turner syndrome, POI) under specialist paediatric endocrinology supervision. Start at very low doses and titrate over 2–3 years to mimic puberty.

Dose adjustments

Renal

No specific adjustment — use with caution in severe renal impairment (fluid retention).

Hepatic

Active liver disease: avoid systemic HRT. Transdermal route can be considered in mild-moderate hepatic impairment under specialist guidance.

Clinical pearls

  • WHI trial (2002): overstated HRT risks — applied to older, obese women starting HRT >10 years after menopause. Current NICE guidance (NG23): HRT for women <60 starting within 10 years of menopause has favourable benefit-risk ratio
  • Transdermal oestrogen does NOT increase VTE risk (avoids hepatic first-pass and coagulation factor upregulation) — preferred over oral for women with VTE risk factors
  • Progestogen must be added in women with a uterus — micronised progesterone (Utrogestan) preferred (safest breast cancer profile vs. synthetic progestogens)
  • Breast cancer risk: combined HRT increases risk; oestrogen-only HRT in hysterectomised women may actually reduce breast cancer risk (MWHS data)

Contraindications

  • Unexplained vaginal bleeding
  • Oestrogen-dependent cancers (active breast cancer, endometrial cancer)
  • VTE history (caution — use transdermal if HRT required)
  • Active liver disease
  • Untreated endometrial hyperplasia
  • Uncontrolled hypertension

Side effects

  • Breast tenderness and swelling
  • Nausea
  • Headache / migraine
  • Fluid retention / bloating
  • VTE (oral route — 2-fold increase; transdermal does not increase VTE risk)
  • Breast cancer (small increase in risk with combined HRT — 1 extra case per 1000 women per year over 5 years)
  • Endometrial cancer (oestrogen-only in women with uterus — must add progestogen)

Interactions

  • Enzyme-inducing drugs (rifampicin, carbamazepine) — reduce efficacy of oral oestrogen
  • Thyroid hormones — HRT may increase thyroxine requirements; monitor TFTs

Monitoring

  • Blood pressure (annually)
  • Breast examination and mammography (as per NHS screening programme)
  • Endometrial assessment if breakthrough bleeding
  • Annual review of ongoing benefit vs. risk

Reference: BNFc; BNF 90; NICE NG23 (Menopause); BMS HRT Guidelines 2020; WHI Trial. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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