ESTRONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ESTRONE (ESTRONE).
Estrone is a natural estrogen that binds to estrogen receptors (ERα and ERβ) in target tissues, modulating gene expression and exerting estrogenic effects on reproductive, skeletal, and cardiovascular systems.
| Metabolism | Metabolized primarily in the liver via hydroxylation by cytochrome P450 enzymes (CYP3A4, CYP1A2, CYP2C9, CYP2C19) and conjugation to glucuronides and sulfates. Estrone is interconvertible with estradiol and estriol. Enterohepatic recirculation occurs. |
| Excretion | Renal (approximately 60-80% as glucuronide and sulfate conjugates), biliary/fecal (20-40%) |
| Half-life | Terminal elimination half-life is 24-36 hours; due to enterohepatic recirculation and slow clearance of conjugates, clinical effects persist for several days after discontinuation. |
| Protein binding | Approximately 96-98% bound to albumin and sex hormone-binding globulin (SHBG) |
| Volume of Distribution | 0.8-1.2 L/kg; indicates extensive distribution into tissues, particularly adipose tissue. |
| Bioavailability | Oral: ~5% due to extensive first-pass metabolism; Intramuscular: 100%; Topical: variable, approximately 10% systemically. |
| Onset of Action | Intramuscular: 1-2 hours; Oral: 2-4 hours; Topical: 1-2 hours |
| Duration of Action | Intramuscular: 3-7 days depending on dose; Oral: 24-48 hours; Topical: 24 hours; long-acting depot formulations may last 2-4 weeks. |
For menopausal hormone therapy: 0.625-5 mg orally once daily; or 0.1-0.5 mg transdermally once weekly; or 2.5-5 mg intramuscularly every 2-4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustments provided; use with caution in severe renal impairment (GFR <30 mL/min) due to potential accumulation of metabolites; monitor estrogenic effects. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). In Child-Pugh class A or B, reduce dose by 50% and monitor liver function; start at lowest effective dose. |
| Pediatric use | Not indicated for routine use; individualize for rare conditions (e.g., delayed puberty) under specialist guidance. Typical starting dose: 0.3-0.625 mg orally once daily; adjust based on response and bone age. |
| Geriatric use | Start at low end of dosing range (e.g., 0.3-0.625 mg orally once daily); consider increased risk of thromboembolism and endometrial cancer; monitor for adverse effects; use shortest duration possible. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ESTRONE (ESTRONE).
| Breastfeeding | Estrone is excreted in human breast milk; M/P ratio not determined. Use during lactation is generally contraindicated as estrogens may suppress milk production and alter milk composition. Alternative agents recommended if breastfeeding. |
| Teratogenic Risk | First trimester: Theoretical risk of fetal harm based on estrogenic effects, but no well-controlled studies. Second and third trimesters: Avoid use due to risk of fetal genital tract abnormalities and potential for other adverse effects. Overall: FDA Pregnancy Category X (contraindicated) unless used for specific conditions like progesterone-resistant recurrent pregnancy loss. |
■ FDA Black Box Warning
Estrogens increase the risk of endometrial cancer in postmenopausal women. Unopposed estrogen use is associated with increased risk of endometrial hyperplasia and carcinoma. Adequate diagnostic measures should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.
| Serious Effects |
["Known or suspected pregnancy","Undiagnosed abnormal genital bleeding","Known or suspected breast cancer (except in selected palliative cases)","Known or suspected estrogen-dependent neoplasia","Active or history of venous thromboembolism (e.g., DVT, pulmonary embolism)","Active arterial thromboembolic disease (e.g., stroke, MI)","Severe hepatic impairment or disease","Hypersensitivity to estrone or any component of the formulation"]
| Precautions | ["Cardiovascular disorders: Increased risk of stroke, DVT, pulmonary embolism, and myocardial infarction, especially in smokers and older women","Malignancy: Increased risk of endometrial cancer (unopposed estrogen) and potential for breast cancer; avoid use in known or suspected estrogen-dependent neoplasia","Dementia: Possible increased risk in women over 65 years","Gallbladder disease: Increased risk of cholelithiasis","Hypertriglyceridemia: May cause severe hypertriglyceridemia with pancreatitis","Hepatic impairment: Use with caution; may be contraindicated in severe disease","Fluid retention: May exacerbate conditions such as asthma, epilepsy, migraine, cardiac or renal dysfunction","Hypocalcemia: Should be used with caution in patients with hypoparathyroidism","Visual abnormalities: Discontinue if sudden vision loss, proptosis, or migraine develops"] |
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| Fetal Monitoring | Monitor maternal blood pressure, liver function, and signs of thromboembolism. In cases of accidental exposure or therapeutic use during pregnancy, fetal ultrasound for genital tract development and appropriate prenatal surveillance. |
| Fertility Effects | Estrone can affect fertility by altering the hypothalamic-pituitary-gonadal axis; chronic use may suppress ovulation and disrupt menstrual cycles. Withdrawal may restore fertility, but long-term effects on fertility are not fully characterized. |