Conjugated estrogens

PREMARIN

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What it isMixture of estrogens from equine urine; vasomotor symptoms and genitourinary atrophy.

Why this oneThe preparation used in the Women’s Health Initiative, so its risks and benefits are the best quantified of any menopausal hormone therapy.

What limits itVTE, stroke and, unopposed, endometrial cancer — add a progestogen if the uterus is present. Oral dosing carries more VTE risk than transdermal.

FDA-approved for

menopausal symptoms (~1942)

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Increased endometrial cancer risk with unopposed estrogen in women with a uterus (add progestin); do not use to prevent cardiovascular disease or dementia; WHI (estrogen-alone): increased stroke and DVT; WHIMS: increased probable dementia at age >=65; estrogen+progestin additionally increased PE, MI, and invasive breast cancer

FDA dosing	Population	Start	Target
Moderate-severe vasomotor symptoms of menopause	Postmenopausal women	0.3 mg QD; adjust to response; continuous or cyclic (e.g., 25 days on/5 off)	Lowest effective dose, reassessed periodically
Moderate-severe vulvar/vaginal atrophy of menopause	Postmenopausal women	0.3 mg QD; adjust to response; continuous or cyclic	Lowest effective dose (consider topical vaginal products if solely vaginal symptoms)
Hypoestrogenism - female hypogonadism	Women	0.3 or 0.625 mg QD, cyclically (e.g., 3 wk on/1 wk off)	Adjusted to symptoms and endometrial responsiveness
Hypoestrogenism - female castration or primary ovarian failure	Women	1.25 mg QD, cyclically	Lowest maintenance dose providing effective control
Breast cancer, palliation only (metastatic disease, selected patients)	Women & men	10 mg TID for at least 3 months	10 mg TID
Advanced androgen-dependent prostate carcinoma, palliation only	Men	1.25-2.5 mg TID	Judged by phosphatase levels and symptoms
Prevention of postmenopausal osteoporosis	Postmenopausal women	0.3 mg QD; adjust to clinical/bone mineral density response; continuous or cyclic	Lowest effective dose

Renal Undefined (effect of renal impairment not studied)

Hepatic Contraindicated in hepatic impairment or disease

Instructions

May take without regard to meals
Use lowest effective dose for shortest duration; re-evaluate periodically
Add a progestin in women with a uterus (endometrial cancer risk); not needed after hysterectomy (except some with history of endometriosis)

Contraindications

Undiagnosed abnormal genital bleeding
Breast cancer or history of breast cancer (except appropriately selected patients treated for metastatic disease)
Estrogen-dependent neoplasia
Active DVT or PE, or history of these
Active arterial thromboembolic disease (e.g., stroke, MI), or history of these
Hepatic impairment or disease
Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

Cautions

Cardiovascular disorders: stroke, DVT (discontinue if these occur or are suspected)
Malignant neoplasms: endometrial cancer (unopposed estrogen), breast cancer
Probable dementia in women >=65 yr
Gallbladder disease (2- to 4-fold risk of surgery)
Severe hypercalcemia in breast cancer with bone metastases - discontinue if it occurs
Visual abnormalities/retinal vascular thrombosis - discontinue pending evaluation for sudden vision loss, proptosis, diplopia, migraine
Anaphylaxis and angioedema reported

Adverse reactions

Abdominal pain
Asthenia
Back pain
Headache
Flatulence
Nausea
Depression
Insomnia
Breast pain
Endometrial hyperplasia
Leucorrhea
Vaginal hemorrhage
Vaginitis

Pregnancy Not indicated for use during pregnancy; epidemiologic data show no increased birth-defect risk from inadvertent early-pregnancy estrogen exposure

Lactation Estrogens present in human milk and can reduce milk production (less likely once breastfeeding established); weigh benefits against maternal need

⚠ BOXED WARNINGS