Estradiol & progesterone (HRT)
Estradiol cypionate / E2, Progesterone · Sex hormones (hormone therapy)
What it is
Hormone-therapy agents — injectable estradiol esters (the core feminizing agent) and progesterone (whose routine role in feminizing therapy remains optional and debated) — which also circulate outside supervised care.
What human evidence shows
Large clinical literature in menopausal HRT and transgender medicine, with monitoring frameworks that are indication- and patient-specific — in supervised care. Unsupervised use discards exactly that monitoring.
Risks
Thromboembolism is the headline estrogen risk (route- and dose-dependent), plus monitoring-dependent items: breast tissue changes, mood effects, fertility impact, and — in unsupervised use — running levels far outside any studied range. Hormone therapy is one of medicine's better-served areas for legitimate clinical access; unsupervised sourcing is all downside here.
Legal status
US: prescription-only.
Evidence base
Not auto-graded. This entry covers several different drugs, or a use the published research was never about, so no single letter honestly describes it. The reading below is real literature — read it against what this page says, not as a score.
Research (12)
- Tailoring transdermal estradiol dose to maximize benefits and minimize risksMenopause · 2026
- Menopausal Hormone Therapy and Cardiovascular Disease: The Role of Formulation, Dose, and Route of DeliveryJ Clin Endocrinol Metab · 2021
- Neuroendocrine mechanisms of mood disorders during menopause transition: A narrative review and future perspectivesMaturitas · 2024
- The rediscovery of estetrol and its implications for estrogen treatmentMenopause · 2025
- Obesity and menopauseBest Pract Res Clin Obstet Gynaecol · 2015
- The route of administration, timing, duration and dose of postmenopausal hormone therapy and cardiovascular outcomes in women: a systematic reviewHum Reprod Update · 2019
- Metabolic Messengers: oestradiolNat Metab · 2025
- Comparison of estrogens and selective estrogen receptor modulators (SERMs) used for menopausal hormone therapyMenopause · 2025
- AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON MENOPAUSE-2017 UPDATEEndocr Pract · 2017
- Association Between Menopause Age and Estradiol-Based Hormone Therapy With Cognitive Performance in Cognitively Normal Women in the CLSANeurology · 2025
- Long-term cognitive effects of menopausal hormone therapy: Findings from the KEEPS Continuation StudyPLoS Med · 2024
- Hormone therapy and phytoestrogensJ Clin Pharm Ther · 1996
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