estradiol hemihydrate + norethisterone acetate: clinical use

Prescribing considerations

• Confirm whether the patient has a uterus and assess menopausal status and bleeding history.
• Assess breast, endometrial, cardiovascular, thromboembolic, hepatic and osteoporosis risks.
• Investigate unexplained bleeding before initiation and assess new, persistent or heavy bleeding during treatment.
• Review benefit and risk periodically and before major surgery or expected prolonged immobilisation.
• Discuss contraception where pregnancy remains possible.

Contraindications and cautions

• Known, previous or suspected breast cancer
• Known or suspected oestrogen-dependent malignancy
• Undiagnosed genital bleeding or untreated endometrial hyperplasia
• Previous or current venous thromboembolism or known thrombophilic disorder
• Active or recent arterial thromboembolic disease
• Acute liver disease, or previous liver disease before tests have normalised
• Porphyria
• Hypersensitivity to an active substance or excipient; selected Estradot Conti patches are also contraindicated with soya or peanut hypersensitivity

Monitoring

• Personal and family history, with examination guided by clinical risk
• Symptom control, adverse effects and ongoing benefit-risk balance
• Breast awareness and appropriate screening
• Unscheduled bleeding
• Blood pressure and relevant hepatic, metabolic or thromboembolic risk factors where indicated
• Thyroid function in patients receiving thyroid replacement

Clinical pharmacology

Estradiol acts through oestrogen receptors. Norethisterone acetate is rapidly converted to norethisterone, which opposes oestrogen-driven endometrial proliferation. Transdermal delivery avoids noticeable hepatic first-pass metabolism, while oral estradiol undergoes substantial gastrointestinal absorption and hepatic metabolism.

Formulation and product differences

• Elleste Duet is an oral sequential product with differently coloured estradiol-only and combined tablets; it contains lactose.
• Evorel Conti and Estradot Conti are continuous combined matrix patches applied below the waist.
• Selected Estradot Conti patches contain partially hydrogenated soybean oil, requiring attention to soya or peanut allergy.
• Patch products differ in composition and labelled release and should not be assumed interchangeable.

Tablet

Route: Oral

Strengths: 1 mg + 0.5 mg, 2 mg + 1 mg