What is the standard sig (prescription instruction) for Premarin (conjugated estrogens) for menopausal symptoms?

Standard Premarin Dosing for Menopausal Symptoms

For postmenopausal women with moderate to severe vasomotor symptoms, Premarin (conjugated equine estrogens) 0.625 mg orally once daily is the standard FDA-studied dose, with mandatory addition of a progestin in women with an intact uterus to prevent endometrial cancer. 1, 2

Dosing Algorithm Based on Uterine Status

Women WITH Intact Uterus

• Premarin 0.625 mg orally once daily PLUS one of the following progestin regimens 1, 2:

  • Preferred: Micronized progesterone 200 mg orally at bedtime (continuous) 2, 3
  • Alternative: Medroxyprogesterone acetate 2.5 mg orally daily (continuous) 1, 4
  • Cyclic option: Medroxyprogesterone acetate 10 mg orally daily for 12-14 days per month 1, 5

• The continuous combined regimen (daily estrogen + daily progestin) typically achieves amenorrhea in 65% of women immediately and in all women by 12-15 months 4

• Micronized progesterone is superior to medroxyprogesterone acetate for sleep quality, improving sleep efficiency by 8% while both equally control menopausal symptoms 3

Women WITHOUT Uterus (Post-Hysterectomy)

• Premarin 0.625 mg orally once daily (estrogen-alone therapy) 1, 2
• No progestin required, which eliminates progestin-related side effects and may reduce breast cancer risk (HR 0.80) 2

Duration and Timing Principles

• Use the lowest effective dose for the shortest duration necessary - this is an FDA mandate, not a suggestion 2
• Most favorable risk-benefit profile exists for women under age 60 OR within 10 years of menopause onset 2
• Initiate therapy at symptom onset; do not delay until after menopause is complete 2
• Annual reassessment is mandatory - attempt dose reduction or discontinuation yearly 2
• For women over 60 or more than 10 years past menopause, HRT initiation is generally contraindicated except for severe refractory symptoms 2

Expected Efficacy

• Premarin 0.625 mg reduces vasomotor symptoms by approximately 75% 2
• Hot flushes decrease from baseline average of 6.7 per day to 0.5 per day by 12 weeks 6
• Continuous improvement occurs with each successive treatment cycle 6, 7

Critical Absolute Contraindications

Before prescribing, verify absence of 2:

• History of breast cancer or other estrogen-dependent neoplasia
• Active liver disease
• History of venous thromboembolism or stroke
• Coronary heart disease or myocardial infarction
• Antiphospholipid syndrome or positive antiphospholipid antibodies
• Undiagnosed abnormal vaginal bleeding

Transdermal Alternative (Preferred Over Oral)

If no contraindications exist, transdermal estradiol 0.05 mg patch (changed twice weekly) is superior to oral Premarin due to 2:

• Avoidance of hepatic first-pass metabolism
• Lower rates of venous thromboembolism
• Lower stroke risk
• More favorable cardiovascular profile

For women with intact uterus using transdermal estradiol, add micronized progesterone 200 mg orally at bedtime 2

Common Pitfalls to Avoid

• Never initiate HRT solely for osteoporosis or cardiovascular disease prevention - this increases morbidity and mortality 2
• Never use higher doses than 0.625 mg without compelling reason - risks increase dose-dependently 2
• Never continue therapy beyond symptom management needs - breast cancer risk increases significantly after 5 years 2
• Never prescribe estrogen alone in women with intact uterus - this causes endometrial hyperplasia and cancer 2
• Do not use compounded "bioidentical" hormones - these lack safety and efficacy data 2

Risk Profile at Standard Dose

Per 10,000 women taking Premarin 0.625 mg + progestin for 1 year 2:

• 7 additional coronary events
• 8 additional strokes
• 8 additional pulmonary emboli
• 8 additional invasive breast cancers
• Balanced against: 6 fewer colorectal cancers, 5 fewer hip fractures, 75% reduction in hot flushes

For estrogen-alone therapy (post-hysterectomy), breast cancer risk is not increased and may be reduced 2