Premarin (Conjugated Estrogens) Prescription

For postmenopausal women with moderate-to-severe vasomotor symptoms and an intact uterus, Premarin must always be prescribed with concurrent progestogen therapy—never as monotherapy—because unopposed estrogen increases endometrial cancer risk 10- to 30-fold after 5 years of use. 1

Standard Prescription Format

For Women WITH an Intact Uterus (Requires Progestogen)

Premarin (conjugated equine estrogens) 0.625 mg

Take 1 tablet by mouth once daily
Dispense: 30 tablets
Refills: 11 (for 1 year with annual reassessment)

PLUS

Micronized progesterone 200 mg

Take 1 capsule by mouth at bedtime for 12–14 consecutive days each month (days 15–28 of cycle)
Dispense: 14 capsules
Refills: 11

Alternative continuous regimen: Micronized progesterone 100 mg nightly without interruption 1

For Women WITHOUT a Uterus (Post-Hysterectomy)

Premarin (conjugated equine estrogens) 0.625 mg

Take 1 tablet by mouth once daily
Dispense: 30 tablets
Refills: 11

No progestogen required; estrogen-alone therapy shows no increased breast cancer risk and may be protective (RR 0.80) 2, 1

Critical Pre-Prescription Requirements

Absolute Contraindications (Must Rule Out)

Personal history of breast cancer 2, 1
Active or history of venous thromboembolism or pulmonary embolism 2, 1
History of stroke or transient ischemic attack 2, 1
Coronary heart disease or myocardial infarction 2, 1
Active liver disease 2, 1
Antiphospholipid syndrome or positive antiphospholipid antibodies 2, 1
Unexplained vaginal bleeding 2
Pregnancy 2

Baseline Assessment Required

Blood pressure measurement (oral estrogen can elevate BP) 1
Confirm non-pregnancy status 1
Document absence of all contraindications 1

Dosing Considerations

Standard Dose

Premarin 0.625 mg daily is the dose studied in the Women's Health Initiative trials and represents the evidence-based standard 1

Lower Dose Option

Premarin 0.3–0.45 mg daily may be considered for women requiring minimal symptom control, though less extensively studied 1

Higher Dose

Doses above 0.625 mg carry incrementally increased cardiovascular and breast cancer risks without proportional symptom benefit 1

Risk-Benefit Profile (Per 10,000 Women-Years)

With Combined Estrogen-Progestogen (Intact Uterus)

Risks:

8 additional invasive breast cancers 2, 1
8 additional strokes 2, 1
8 additional pulmonary emboli 2, 1
7 additional coronary events 2, 1

Benefits:

75% reduction in vasomotor symptom frequency 2, 1
6 fewer colorectal cancers 2, 1
5 fewer hip fractures 2, 1

With Estrogen-Alone (Post-Hysterectomy)

No increased breast cancer risk (RR 0.80) 2, 1
8 additional strokes 2, 1
8 additional venous thromboembolic events 2, 1
5 fewer hip fractures 2, 1

Duration and Monitoring

Treatment Duration

Use the lowest effective dose for the shortest duration necessary to control symptoms 2, 1
Breast cancer risk emerges after 4–5 years of combined therapy 1
Stroke and VTE risks appear within 1–2 years 1

Annual Reassessment Protocol

Review symptom control and medication adherence 1
Measure blood pressure 1
Screen for new contraindications 1
Evaluate any abnormal vaginal bleeding (if uterus intact) 1
Attempt dose reduction or discontinuation once symptoms are controlled 1

Age-Specific Guidance

Most favorable risk-benefit: Women <60 years or within 10 years of menopause 2, 1
At age 65: Reassess necessity and attempt discontinuation; initiating HRT after 65 is contraindicated 1

Patient Counseling Points

Emergency Warning Signs (Seek Immediate Care)

Sudden chest pain or severe shortness of breath (possible pulmonary embolism) 1
Acute neurological deficits: severe headache, vision changes, speech difficulty, weakness (possible stroke) 1
Leg pain, swelling, warmth, or redness (possible deep vein thrombosis) 1

Contact Provider Within 24 Hours

Heavy vaginal bleeding 1
New breast lump 1

Expected Timeline for Symptom Relief

Vasomotor symptoms: 50% reduction within 2–4 weeks, maximal benefit by 8–12 weeks 1
Vaginal dryness: improvement within 2–4 weeks, maximal benefit by 8–12 weeks 1

Important Clinical Caveats

Why Oral Premarin Is Not First-Line

Transdermal estradiol is preferred over oral Premarin because:

Oral estrogen increases stroke risk by 28–39%; transdermal does not 1
Oral estrogen raises VTE risk 2–4-fold; transdermal does not 1
Oral estrogen increases gallbladder disease risk (RR 1.61–1.79); transdermal does not 1

However, Premarin remains appropriate when:

Patient specifically requests oral therapy after counseling on risks 1
Transdermal formulations are not tolerated or accessible 1
Patient has no additional VTE risk factors (obesity, smoking, thrombophilia) 1

Progestogen Selection Rationale

Micronized progesterone is preferred over medroxyprogesterone acetate because it has superior breast safety while maintaining endometrial protection 1
Progestogen must be given for at least 12 days per cycle; shorter durations increase endometrial cancer risk 1.8-fold 1

USPSTF Grade D Recommendation

Never prescribe Premarin solely for osteoporosis or cardiovascular disease prevention in asymptomatic women—this carries a Grade D recommendation (recommends against) because harms outweigh benefits 2, 1

Special Populations

Premature or Surgical Menopause (<45 Years)

Initiate HRT immediately at diagnosis/post-surgery 1
Continue at least until age 51 (average natural menopause), then reassess 1
Risk-benefit profile is highly favorable in this population 1

Smokers Over Age 35

Smoking significantly amplifies cardiovascular and thrombotic risks with oral estrogen 1
Smoking cessation is the single most important intervention before considering HRT 1
If HRT is essential, transdermal estradiol is mandatory (not oral Premarin) 1

Obese Women (BMI ≥30)

Oral estrogen raises VTE risk 2–4-fold, further amplified by obesity's baseline 2–3-fold VTE risk 1
Never prescribe oral Premarin to obese women—use transdermal estradiol instead 1

Alternative to Premarin

If transdermal therapy is preferred (recommended first-line):

Estradiol transdermal patch 0.05 mg

Apply 1 patch twice weekly (every 3–4 days)
Dispense: 8 patches
Refills: 11

PLUS (if uterus intact)