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. |
| Molecular Weight | 270.37 |
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 | Contraindicated; risk of fetal harm based on animal studies and limited human data. Estrogen exposure during early pregnancy is associated with increased risk of congenital anomalies. |
| 2nd trimester | Contraindicated; use during second trimester is associated with potential adverse effects on fetal development, including genitourinary tract abnormalities. |
| 3rd trimester | Contraindicated; exposure in late pregnancy may lead to delayed parturition, fetal distress, and long-term reproductive tract abnormalities (e.g., vaginal adenosis, clear cell adenocarcinoma in female offspring). |
Clinical note
Comprehensive clinical and safety monograph for NATURAL ESTROGENIC SUBSTANCE-ESTRONE (NATURAL ESTROGENIC SUBSTANCE-ESTRONE).
| Placental transfer | Estrone crosses the placenta. Cord blood levels can reach maternal levels, indicating significant transfer. Animal studies confirm placental passage with potential for fetal toxicity. |
| Breastfeeding |
■ 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 pregnancyUndiagnosed abnormal genital bleedingKnown or suspected estrogen-dependent neoplasia (e.g., breast cancer, endometrial cancer)Active thromboembolic disorder or history of thromboembolism (e.g., deep vein thrombosis, pulmonary embolism)Known hypersensitivity to estrone
| 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. |
| Food/Dietary | Grapefruit juice may increase estrone levels; avoid concomitant use. Excessive alcohol intake may alter estrogen metabolism. High-fat meals may affect absorption of oral formulations. |
Loading safety data…
| Estrone is excreted in human milk and may reduce milk production and quality. Use during breastfeeding is not recommended. If use is necessary, monitor infant for estrogenic effects such as breast enlargement and vaginal bleeding. The American Academy of Pediatrics considers estrogens as compatible with breastfeeding, but alternatives are preferred. |
| Lactation Rating | L3 - Limited data; potential adverse effects. Some sources classify as 'Avoid' due to risk of reduced milk supply. |
| 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 | 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. |
| Clinical Pearls | For hormone replacement therapy, start with lowest effective dose. Use for vasomotor symptoms; not for primary or secondary prevention of cardiovascular disease. Contraindicated in breast cancer, active thromboembolic disease, and pregnancy. Monitor for endometrial hyperplasia with unopposed use. |
| Patient Advice | Take exactly as prescribed; do not skip doses unless directed. · Report any unusual vaginal bleeding, breast lumps, or leg swelling/pain immediately. · Do not use if pregnant or breastfeeding. · Some formulations may interact with herbal supplements like St. John's Wort. · Smoking increases risk of thromboembolic events; advise cessation. |