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Combined HRT (oestrogen + progestogen) Pregnancy: §4.6: not indicated during pregnancy. If pregnancy occurs during treatment, withdraw immediately. Data on a limited number of exposed pregnancies indicate no adverse effects of medroxyprogesterone acetate on the foetus; animal studies have shown reproductive toxicity and the potential risk for humans is unknown. Most epidemiological studies relevant to inadvertent foetal exposure to combinations of oestrogens and progestagen indicate no teratogenic or foetotoxic effect. Not indicated during lactation.

Estradiol with medroxyprogesterone

Brand names: Indivina, Tridestra

A combined hormone replacement therapy combining estradiol with the progestogen medroxyprogesterone acetate, used for menopausal symptom relief in women who have a uterus.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: One tablet each day (initiate with Indivina 1 mg/2.5 mg — 1 mg estradiol valerate with 2.5 mg medroxyprogesterone acetate)
Route: Oral
Frequency: Once daily without a tablet-free interval, taken at approximately the same time each day
SOURCE PRODUCT: Indivina 1 mg/2.5 mg tablets — a continuous combined HRT regimen in which oestrogen and progestagen are given every day without interruption. TITRATION: treatment is recommended to be initiated with Indivina 1 mg/2.5 mg and the dosage then adjusted to individual need depending on clinical response. Medroxyprogesterone acetate 2.5 mg is usually sufficient to prevent breakthrough bleeding; if breakthrough bleeding occurs and persists and endometrial abnormality has been ruled out, the dose can be increased to 5 mg (Indivina 1 mg/5 mg tablet). If 1 mg of estradiol valerate is not sufficient to alleviate oestrogen deficiency symptoms, the dose can be increased to 2 mg (Indivina 2 mg/5 mg tablet). The effect of oestrogen on bone mineral density is dose dependent, so the effect of 1 mg estradiol valerate may be less than with 2 mg. For initiation and continuation of treatment of postmenopausal symptoms the lowest effective dose for the shortest duration should be used. STARTING: in women with amenorrhoea not taking HRT, or women switching from another continuous combined HRT product, treatment may be started on any day; women switching from a cyclic HRT regimen should start one week after completion of the cycle. MISSED DOSE: discard the forgotten tablet — forgetting a dose may increase the likelihood of breakthrough bleeding and spotting.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Known, past or suspected breast cancer
  • Known or suspected oestrogen-dependent malignant tumours (e.g. endometrial cancer)
  • Undiagnosed genital bleeding
  • Untreated endometrial hyperplasia
  • Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism)
  • Known thrombophilic disorders (e.g. protein C, protein S or antithrombin deficiency)
  • Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction)
  • Acute liver disease or a history of liver disease as long as liver function tests have failed to return to normal
  • Hypersensitivity to the active substances or to any excipient
  • Porphyria

Side effects

  • Breast pain/tension — the most frequently reported effect, in 10.6% of users in clinical trials; also unscheduled vaginal bleeding or spotting, vaginal discharge, vulval/vaginal disorder and menstrual disorder (common)
  • Headache and dizziness (common); migraine, paraesthesia and tremor (uncommon)
  • Hot flushes (common); hypertension and superficial phlebitis (uncommon); venous thromboembolism (deep leg or pelvic venous thrombosis and pulmonary embolism) and cerebral ischaemic events (rare)
  • Nausea, vomiting, stomach cramps and flatulence (common); abdominal pain and bloating (rare)
  • Oedema, weight increase or decrease (common); depression, nervousness and lethargy (common)
  • Alterations in liver function and biliary flow (uncommon); cholestatic jaundice (rare); benign breast and endometrial neoplasms (common)

Clinical monograph

How it works

Estradiol restores oestrogenic activity to relieve menopausal symptoms while medroxyprogesterone acetate counters oestrogen-induced endometrial proliferation to protect the endometrium.

Prescribing in practice

  • The medroxyprogesterone component is required to prevent endometrial hyperplasia and carcinoma from unopposed oestrogen in women with an intact uterus.
  • Evaluate venous thromboembolism, stroke and breast cancer risk before initiation and review at least annually.
  • Avoid in active or previous thromboembolic disease, oestrogen-dependent cancers and undiagnosed vaginal bleeding.

Monitoring

Review symptoms, blood pressure and bleeding pattern periodically, and investigate any unscheduled vaginal bleeding.

Counselling the patient

  • Report unexpected vaginal bleeding, new breast lumps, or possible clot symptoms.
  • Take the combined preparation as prescribed and do not omit the progestogen component.
  • Continue to attend breast and cervical screening when invited.

Evidence & guidelines

Combined oestrogen-progestogen hormone replacement therapy is supported by NICE menopause guidance for symptom control with individualised risk assessment.

Reference: NICE NG23; British Menopause Society; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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