What does Hormone Replacement Therapy (HRT) consist of for a postmenopausal woman who has undergone a hysterectomy?

Hormone Replacement Therapy After Hysterectomy

For postmenopausal women who have undergone a hysterectomy, HRT consists of estrogen-alone therapy without any progestin, as there is no uterus requiring endometrial protection. 1

Preferred Estrogen Formulation and Dosing

Transdermal 17β-estradiol 50-100 mcg daily is the first-line choice over oral formulations, as it avoids hepatic first-pass metabolism, provides superior safety regarding thrombotic risk, and has more favorable effects on lipids and blood pressure. 1 The standard approach is a 50 μg patch applied twice weekly. 2

Oral Alternatives (if transdermal not feasible):

• 17β-estradiol 1-2 mg daily 1
• Conjugated equine estrogens 0.625-1.25 mg daily 1

Critical Principle: No Progestin Required

Adding progestin to estrogen therapy in women without a uterus introduces avoidable harms, including increased breast cancer risk, with no additional benefit for vasomotor symptoms or vaginal atrophy. 1 Progestin should only be added in rare circumstances, such as supracervical hysterectomy where the cervical stump remains and contains endometrial tissue. 1

Age and Timing Considerations

The risk-benefit profile is most favorable for women under 60 years of age or within 10 years of menopause onset. 2 Long-term follow-up from the Women's Health Initiative demonstrates lower cardiovascular and breast cancer risks with estrogen-alone therapy in younger women compared to older women. 1

For Women Over 60 or >10 Years Post-Menopause:

• Use the absolute lowest effective dose 2
• Plan for the shortest possible duration 2
• Reassess necessity and attempt discontinuation 2
• Avoid initiating HRT for chronic disease prevention, as it increases morbidity and mortality 2

Special Populations

Women with History of Low-Risk Endometrial Cancer:

For Stage I-II, low-grade endometrial cancer, estrogen replacement therapy is reasonable, as randomized trials show no increased recurrence rates. 1 However, wait 6-12 months after completion of adjuvant treatment before initiating hormone therapy. 1

Women with Premature Surgical Menopause:

Women with surgical menopause before age 45 should start HRT immediately post-surgery unless contraindications exist, and continue at least until age 51, then reassess. 2 This prevents accelerated cardiovascular risk and bone loss. 2

Absolute Contraindications

Do not prescribe estrogen therapy to women with: 1, 2

• History of breast cancer
• Active or recent thromboembolic events
• Current smoking status (especially over age 35)
• History of stroke or coronary heart disease
• Active liver disease
• Antiphospholipid syndrome

Benefits and Risks

Benefits of Estrogen-Alone Therapy:

• 75% reduction in vasomotor symptom frequency 2
• 22-27% reduction in all clinical fractures 2
• No increased breast cancer risk (may even be protective with RR 0.80) 2, 3
• Prevention of accelerated bone loss 2

Risks:

• 8 additional strokes per 10,000 women-years 2
• 8 additional venous thromboembolic events per 10,000 women-years 2
• Increased gallbladder disease risk (RR 1.48-1.8) 2

Monitoring and Duration

No routine laboratory monitoring (estradiol levels, FSH) is required—management is symptom-based. 2 Annual clinical review should assess compliance and ongoing symptom burden. 2

Use the lowest effective dose for the shortest duration consistent with treatment goals. 3 Attempt dose reduction or discontinuation once symptoms are controlled, with reevaluation at age 65. 2

Vaginal Symptoms

For isolated genitourinary symptoms, low-dose vaginal estrogen preparations (rings, suppositories, creams) can be used without systemic progestin, as they provide minimal systemic absorption. 1, 2 These can be used concurrently with systemic estrogen therapy if needed. 2

Common Pitfalls to Avoid

• Never add progestin routinely to estrogen therapy in women without a uterus—this increases breast cancer risk unnecessarily 1
• Never use oral estrogen when transdermal is available—transdermal has superior safety profile regarding thrombosis 1
• Never deny estrogen therapy to all women with prior low-risk endometrial cancer—evidence shows safety in these cases 1
• Never initiate HRT solely for chronic disease prevention in asymptomatic women—this is explicitly contraindicated 2