ESTROVIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ESTROVIS (ESTROVIS).
Estrovis (estropipate) acts by binding to estrogen receptors (ERα and ERβ), leading to activation of estrogen-responsive genes. It increases hepatic synthesis of sex hormone-binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins, and suppresses gonadotropin secretion via negative feedback on the hypothalamic-pituitary axis.
| Metabolism | Estropipate is hydrolyzed to estrone, which undergoes extensive hepatic metabolism via cytochrome P450 3A4 (CYP3A4) and other enzymes. Estrone is further metabolized to estradiol and estriol. Conjugation occurs with glucuronic acid and sulfate, and metabolites are excreted primarily in urine. |
| Excretion | Renal: 60-70% as glucuronide and sulfate conjugates; Fecal/biliary: 20-30% as conjugated metabolites. |
| Half-life | Terminal elimination half-life: 12-18 hours (mean 15 hours). Clinical context: Supports once-daily dosing; steady-state achieved within 3-5 days. |
| Protein binding | High: 98-99% bound to serum albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Apparent Vd: 0.7-1.0 L/kg, indicating extensive distribution into tissues (e.g., breast, adipose, reproductive organs). |
| Bioavailability | Oral: 5-10% due to extensive first-pass metabolism; Transdermal: 10-20% relative to intravenous. |
| Onset of Action | Oral: 2-4 hours for reduction in vasomotor symptoms; Transdermal: 4-8 hours for initial clinical effect. |
| Duration of Action | Oral: 24 hours (symptom control); Transdermal: 3-4 days (patch replacement interval, with therapeutic levels maintained for 7 days). |
| Molecular Weight | 272.38 |
1 mg orally once daily, continuous dosing cycle (no placebo week).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate impairment (eGFR ≥30 mL/min). Not studied in severe impairment (eGFR <30 mL/min) or dialysis; use contraindicated. |
| Liver impairment | Contraindicated in Child-Pugh class B or C. For Child-Pugh class A, no dose adjustment necessary; monitor liver function. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; however, clinical studies included limited patients >65 years. Use with caution due to increased risk of thromboembolic events and cognitive effects. |
| 1st trimester | Contraindicated due to risk of teratogenicity (females with Y-chromosome may be at increased risk for hypospadias). |
| 2nd trimester | Contraindicated due to risk of fetal harm; may cause feminization of male fetus. |
| 3rd trimester | Contraindicated due to risk of fetal harm; may cause feminization of male fetus. |
Clinical note
Comprehensive clinical and safety monograph for ESTROVIS (ESTROVIS).
| Placental transfer | Estradiol crosses the placenta; transfer of exogenous estrogens is significant. |
| Breastfeeding | Estradiol is excreted in human milk; monitor infant for estrogenic effects (e.g., breast tenderness, vaginal bleeding). Use only if clearly needed. |
| Lactation Rating |
■ FDA Black Box Warning
Estrogen therapy, alone or in combination with progestins, should not be used to prevent cardiovascular disease or dementia. The Women's Health Initiative (WHI) studies reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50-79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo. The WHI study of CE alone reported an increased risk of stroke and deep vein thrombosis. The Women's Health Initiative Memory Study (WHIMS) reported an increased risk of probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with CE plus MPA relative to placebo. It is unknown whether this finding applies to younger postmenopausal women or to estrogens alone.
| Serious Effects |
Known or suspected pregnancyUndiagnosed abnormal genital bleedingKnown or suspected estrogen-dependent neoplasia (e.g., breast cancer)Active thromboembolic disordersPorphyria
| Precautions | Cardiovascular disorders: Increased risk of stroke, DVT, PE, and MI., Malignant neoplasms: Increased risk of endometrial cancer (use with progestin in women with a uterus), breast cancer, and ovarian cancer., Gallbladder disease: Increased risk., Hypertriglyceridemia: Pancreatitis risk in women with elevated triglycerides., Hepatic effects: Monitor liver function; avoid in active liver disease., Fluid retention: Caution in cardiac or renal dysfunction., Hypocalcemia: May be exacerbated., Endometriosis: Malignant transformation risk with unopposed estrogen., Hereditary angioedema: Exacerbation possible., Ophthalmologic effects: Discontinue if sudden vision loss occurs., Dementia: Increased risk in women ≥65 years (WHIMS). |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | FDA Category X. First trimester: Significant risk of congenital anomalies including cardiovascular defects, neural tube defects, and limb reduction defects. Second and third trimesters: Increased risk of urogenital tract abnormalities, vaginal adenosis, and clear cell adenocarcinoma in female offspring. Avoid in pregnancy. |
| Fetal Monitoring | Monitor fetal development with ultrasound during pregnancy if inadvertent exposure occurs. Assess for signs of estrogenic effects in neonates. Monitor maternal blood pressure, liver function, and signs of thromboembolism. |
| Fertility Effects | Estrogens can decrease fertility by inhibiting gonadotropin secretion, disrupting ovulation. Long-term use may impair fertility; effect is reversible upon discontinuation. |
| Food/Dietary | Grapefruit juice may increase estrogen levels; avoid excessive consumption. No other significant food interactions documented. |
| Clinical Pearls | ESTROVIS is a synthetic non-steroidal estrogen used for menopausal hormone therapy. Avoid in patients with known or suspected estrogen-dependent neoplasia. Monitor for thromboembolic events, especially in smokers or those with hypertension. Use lowest effective dose for shortest duration. May increase risk of gallbladder disease. Do not use in pregnancy. |
| Patient Advice | Take exactly as prescribed; do not change dose or stop without consulting your doctor. · Report any unusual vaginal bleeding, chest pain, shortness of breath, or leg swelling immediately. · Avoid smoking, as it increases the risk of blood clots with estrogen use. · This medication does not protect against HIV or other sexually transmitted infections. · Inform your doctor if you become pregnant or plan to become pregnant; estrogen is contraindicated in pregnancy. · Regular breast exams and mammograms are recommended while on this therapy. |