What is the appropriate use of hormone replacement therapy (HRT) in menopausal women?

Hormone Replacement Therapy (HRT) for Menopausal Women

Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms and vaginal atrophy, but should be used at the lowest effective dose for the shortest duration needed due to associated risks. 1

Patient Selection and Appropriate Use

Indications for HRT

• Moderate to severe vasomotor symptoms (hot flashes, night sweats)
• Vulval and vaginal atrophy
• Prevention of osteoporosis (when other medications are not appropriate)

Contraindications

• History of hormone-dependent cancers (breast, uterine) 1
• Active liver disease 1
• Recent or active venous thromboembolism 1
• History of prostate cancer 1

Treatment Approach

Key Principles

1. Use lowest effective dose for shortest duration 1, 2
2. Women with intact uterus must receive progestogen with estrogen to prevent endometrial cancer 1, 2
3. Reevaluate need for therapy every 3-6 months 1, 2
4. More favorable benefit-risk ratio when started in early menopause (within 10 years or before age 60) 1

Dosing Regimens

For Women with Intact Uterus

• Cyclic/Sequential Regimen:

  • Estradiol 1-2 mg daily 1, 2
  • Plus progesterone for 12-14 days per month:
    • Micronized progesterone 200 mg orally/vaginally for 12-14 days 1
    • OR medroxyprogesterone acetate 10 mg for 12-14 days 1

• Continuous Combined Regimen:

  • Estradiol 1-2 mg daily 1, 2
  • Plus daily progestogen:
    • Medroxyprogesterone acetate minimum 2.5 mg daily 1

For Women Without Uterus

• Estradiol 1-2 mg daily without progestogen 2

Route of Administration

• Transdermal estradiol (0.025-0.0375 mg/day patch) is preferred due to lower cardiovascular and thrombotic risk 1
• Oral estradiol is an alternative (1-2 mg daily) 1, 2

Risks and Benefits

Benefits

• Most effective treatment for vasomotor symptoms 1, 3
• Effective for vaginal atrophy 1, 3
• Prevention of osteoporosis 1, 2

Risks

• Breast cancer (hazard ratio 1.26) 1
• Venous thromboembolism (RR 2.14) 1
• Stroke (RR 1.12) 1
• Gallbladder disease (RR 1.8-2.5) 1
• Urinary incontinence 1

Monitoring and Follow-up

• Initial follow-up at 8-10 weeks after starting treatment 1
• Regular reassessment every 3-6 months 1, 2
• Annual comprehensive assessment of risks and benefits 1
• For women with uterus: endometrial sampling when indicated for abnormal vaginal bleeding 2

Non-Hormonal Alternatives

• Calcium and vitamin D supplementation 1
• Weight-bearing exercise 1
• Diet modification 1
• SSRIs/SNRIs (paroxetine, venlafaxine) 1
• Gabapentin 1
• Clonidine 1
• Local vaginal moisturizers and lubricants (first-line for vaginal symptoms) 1

Common Pitfalls to Avoid

1. Prescribing unopposed estrogen to women with intact uterus - significantly increases endometrial cancer risk 1
2. Continuing therapy indefinitely - attempt to discontinue or taper medication every 3-6 months 2
3. Overlooking transdermal options - transdermal routes have less impact on coagulation 4
4. Starting with high doses - begin with lowest effective dose and titrate as needed 1, 2
5. Prescribing HRT for cardiovascular disease prevention - not indicated for this purpose 5, 6

Special Considerations

• Micronized progesterone is associated with lower cardiovascular and thrombotic risk 1
• Lower doses of conjugated estrogens (0.3 mg) may be as effective as higher doses (0.625 mg) with fewer side effects 6
• Women with premature menopause who begin HRT before age 50 may have significant longevity advantages 4