NATURAL ESTROGENIC SUBSTANCE-ESTRONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NATURAL ESTROGENIC SUBSTANCE-ESTRONE (NATURAL ESTROGENIC SUBSTANCE-ESTRONE).
Estrone binds to and activates estrogen receptors (ERα and ERβ), leading to modulation of gene transcription and subsequent estrogenic effects on target tissues.
| Metabolism | Primarily hepatic via cytochrome P450 enzymes, including CYP1A2 and CYP3A4; undergoes oxidation, hydroxylation, and conjugation (glucuronidation and sulfation). |
| Excretion | Renal: ~50% (as glucuronide and sulfate conjugates), Biliary/Fecal: ~50% (enterohepatic recirculation). |
| Half-life | Terminal half-life: 24-48 hours (prolonged due to enterohepatic recirculation and tissue distribution). |
| Protein binding | ~80% bound, primarily to albumin (60%) and sex hormone-binding globulin (SHBG, 20%). |
| Volume of Distribution | Vd: ~10-15 L/kg (extensive tissue distribution, particularly adipose tissue). |
| Bioavailability | Oral: 5-10% (extensive first-pass metabolism); IM: 100%; Transdermal: 5-20% (variable). |
| Onset of Action | Oral: 2-4 hours; IM: 1-2 hours; Transdermal: 4-8 hours. Clinical effects (e.g., vasomotor symptom relief) may take 2-4 weeks. |
| Duration of Action | Oral: 24 hours; IM: 7-14 days for depot formulations; Transdermal: 7 days. Continuous therapy required for sustained effect. |
0.1 to 0.5 mg intramuscularly 2 to 3 times per week for estrogen replacement therapy
| Dosage form | INJECTABLE |
| Renal impairment | No specific dosing adjustment recommended; use caution in severe renal impairment due to potential fluid retention |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated |
| Pediatric use | Not indicated for use in pediatric patients; no established dosing guidelines |
| Geriatric use | Initiate at lowest effective dose; monitor for cardiovascular and thromboembolic events; no specific dose adjustment required but use with caution |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NATURAL ESTROGENIC SUBSTANCE-ESTRONE (NATURAL ESTROGENIC SUBSTANCE-ESTRONE).
| Breastfeeding | Contraindicated during breastfeeding due to suppression of lactation and potential hormone transfer to infant. M/P ratio not established. |
| Teratogenic Risk | First trimester: Increased risk of congenital anomalies, including cardiovascular and neural tube defects. Second and third trimesters: Fetal feminization, genitourinary tract abnormalities, and potential for delayed developmental milestones. |
| Fetal Monitoring |
■ FDA Black Box Warning
Estrogens should not be used to prevent cardiovascular disease or dementia. Increased risk of endometrial cancer in women with intact uterus; use progestin if uterus is intact. Increased risk of stroke, deep vein thrombosis, pulmonary embolism, and myocardial infarction. Increased risk of invasive breast cancer.
| 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 past history of venous thromboembolism (e.g., DVT, PE); active or past history of arterial thromboembolism (e.g., stroke, MI); known liver impairment or disease; known hypersensitivity to estrone or any component; known protein C, protein S, or antithrombin deficiency or other thrombophilic disorders.
| Precautions | Cardiovascular disorders (e.g., stroke, DVT, PE, MI); elevated blood pressure; hypertriglyceridemia; impaired liver function; cholestatic jaundice; gallbladder disease; increased risk of endometrial cancer; breast cancer risk; dementia; fluid retention; hypocalcemia; exacerbation of endometriosis; hereditary angioedema; pre-existing uterine leiomyoma; use during pregnancy should be avoided. |
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| Monitor fetal growth by ultrasound, amniotic fluid index, and non-stress testing. Assess maternal blood pressure, liver function, and coagulation profile. |
| Fertility Effects | May impair fertility by disrupting ovulatory cycles and endometrial receptivity. Long-term use can cause anovulation and amenorrhea. |