Rankings / Hormones & Endocrine
Estetrol (E4) for menopause
Hormones & Endocrine · Native estrogen (NEST)
Tier B
Bottom line
Read Off Label grades Estetrol (E4) for menopause as B (6.6/10) based on strong evidence, med-high benefit magnitude, and a med-risk safety profile.
Estetra/Mithra (Donesta; licensed to Gedeon Richter).
Typical use: Oral 15-20 mg/day (menopause trials) — Rx.
What this is
Estetra/Mithra (Donesta; licensed to Gedeon Richter). E4COMFORT I and II Phase 3 (n~640): significant reductions in moderate-severe vasomotor symptom frequency and severity at weeks 4 and 12 vs placebo. Already approved as the contraceptive Nextstellis/Drovelis. Menopause launch expected 2026, an option for women with synthetic-HRT contraindications. Industry-sponsored.
Mechanism
Estetrol, a native fetal estrogen with tissue-selective estrogen-receptor activity and minimal hepatic impact, apparently with lower thrombotic-marker effect than synthetic or conjugated estrogens.
Dose & route
Oral 15-20 mg/day (menopause trials)
Citations
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Common questions
- Does Estetrol (E4) for menopause work?
- Read Off Label rates the evidence for Estetrol (E4) for menopause as Strong and the benefit magnitude as med-high, producing an overall grade of B (6.6/10). Estetra/Mithra (Donesta; licensed to Gedeon Richter).
- Is Estetrol (E4) for menopause safe?
- Estetrol (E4) for menopause has a med risk profile in published human data. Legal status: Rx (approved as contraceptive; menopause indication Phase 3 / filing). This is not medical advice — see the disclaimer.
- What is the typical dose for Estetrol (E4) for menopause?
- Oral 15-20 mg/day (menopause trials)
- How does Estetrol (E4) for menopause work?
- Estetrol, a native fetal estrogen with tissue-selective estrogen-receptor activity and minimal hepatic impact, apparently with lower thrombotic-marker effect than synthetic or conjugated estrogens.
This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.