What is the recommended dose of Menopausal Hormone Therapy (MHT) for a 55-year-old postmenopausal woman with and without a hysterectomy?

Recommended Doses of Menopausal Hormone Therapy

For postmenopausal women with an intact uterus, use oral conjugated equine estrogen 0.625 mg daily plus medroxyprogesterone acetate 2.5 mg daily (continuous combined) or transdermal estradiol 50 μg daily with micronized progesterone 200 mg at bedtime; for women after hysterectomy, use estrogen-alone therapy with oral conjugated equine estrogen 0.625 mg daily or transdermal estradiol 50 μg daily. 1, 2, 3

Dosing for Women WITH an Intact Uterus

Combined estrogen-progestin therapy is mandatory to prevent endometrial hyperplasia and cancer, which has a relative risk of 2.3 escalating to 9.5 after 10 years of unopposed estrogen use. 4

First-Line Regimen (Transdermal Route Preferred)

• Transdermal estradiol 50 μg daily (patch changed twice weekly) PLUS micronized progesterone 200 mg orally at bedtime 2, 5
• Transdermal delivery avoids hepatic first-pass metabolism, resulting in lower rates of venous thromboembolism, stroke, and cardiovascular events compared to oral formulations 2
• Micronized progesterone is preferred over medroxyprogesterone acetate due to lower breast cancer risk and thrombotic risk 2

Alternative Oral Regimen

• Oral conjugated equine estrogen 0.625 mg daily PLUS medroxyprogesterone acetate 2.5 mg daily (continuous combined) 1, 5
• This was the specific dose studied in the Women's Health Initiative trials, providing adequate endometrial protection with only 6% incidence of hyperplasia over 36 months compared to 64% with estrogen alone 5
• Alternative progestin dosing: medroxyprogesterone acetate 10 mg daily for 10-14 days each month (sequential/cyclic therapy) 5

Progestin Administration Options

• Continuous combined therapy (daily estrogen + daily progestin) minimizes breakthrough bleeding 4
• Sequential/cyclic therapy (daily estrogen with progestin for 10-14 days per month) may result in monthly withdrawal bleeding 4

Dosing for Women WITHOUT a Uterus (Post-Hysterectomy)

Estrogen-alone therapy is appropriate and safe, with no need for progestin and a small reduction in invasive breast cancer risk compared to combined therapy. 1, 4

First-Line Regimen (Transdermal Route Preferred)

• Transdermal estradiol 50 μg daily (patch changed twice weekly) 2
• Preferred due to lower thrombotic and cardiovascular risk profile 2

Alternative Oral Regimen

• Oral conjugated equine estrogen 0.625 mg daily 1, 3
• This dose was specifically studied in WHI trials and demonstrated efficacy with established risk profiles 1
• Alternative: 17β-estradiol 1-2 mg daily 3

Dose Adjustment Principles

Starting and Titration Strategy

• Always start at the lowest effective dose for the indication 3
• Initial dosage range for oral estradiol is 1-2 mg daily, adjusted to control symptoms 3
• For transdermal estradiol, start with 50 μg daily patches; ultra-low-dose 14 μg daily has demonstrated efficacy for women requiring lower doses 2
• Determine the minimal effective dose for maintenance therapy through titration 3

Duration and Reassessment

• Use the lowest effective dose for the shortest duration consistent with treatment goals 2, 3
• Patients should be reevaluated periodically at 3-6 month intervals to determine if treatment is still necessary 3
• Attempts to discontinue or taper medication should be made at 3-6 month intervals 3
• Administration should be cyclic (e.g., 3 weeks on and 1 week off) 3

Critical Risk-Benefit Context by Dose

Combined Estrogen-Progestin (CEE 0.625 mg + MPA 2.5 mg)

For every 10,000 women taking this regimen for 1 year: 1, 2

• Harms: 7 additional coronary events, 8 more strokes, 8 more pulmonary emboli, 8 more invasive breast cancers
• Benefits: 6 fewer colorectal cancers, 5 fewer hip fractures, 75% reduction in vasomotor symptom frequency

Estrogen-Alone (CEE 0.625 mg)

For every 10,000 women taking this regimen for 1 year: 1

• Harms: 8 additional strokes, 8 additional venous thromboembolic events
• Benefits: 5 fewer hip fractures, 75% reduction in vasomotor symptoms, small reduction in breast cancer risk (RR 0.80)

Common Pitfalls to Avoid

• Never use higher doses than necessary to control symptoms, as risks including stroke, VTE, and breast cancer increase with dose and duration 2
• Avoid compounded bioidentical hormones including pellets, as they lack data supporting safety and efficacy 2, 5
• Do not initiate HRT solely for chronic disease prevention in asymptomatic women—this is explicitly contraindicated and increases morbidity and mortality 2
• Never prescribe oral estrogens to women with moderate-to-high cardiovascular risk—use transdermal formulations instead 2
• Do not continue HRT beyond symptom management needs, as breast cancer risk increases significantly beyond 5 years of use 2

Special Population Considerations

Women Under 60 or Within 10 Years of Menopause

• The risk-benefit profile is most favorable in this population 2
• Standard doses as outlined above are appropriate 2

Women Over 60 or More Than 10 Years Past Menopause

• Do not initiate HRT in this population for chronic disease prevention 2
• If already on HRT, reassess necessity and attempt discontinuation 2
• If continuation is deemed essential, reduce to the absolute lowest effective dose 2

Women with Surgical Menopause Before Age 50

• Should start HRT immediately post-surgery unless contraindications exist 2
• Continue at least until average age of natural menopause (51 years), then reassess 2
• Use estrogen-alone therapy if hysterectomy was performed 2