When should estrogen or progesterone (hormone replacement therapy) be prescribed?

When to Prescribe Estrogen or Progesterone (Hormone Replacement Therapy)

Hormone replacement therapy should be prescribed primarily for moderate to severe menopausal symptoms in women who are within 10 years of menopause onset and under 60 years of age, while avoiding use in women with contraindications or those at elevated risk for cardiovascular disease or stroke. 1, 2

Primary Indications for HRT

• Vasomotor symptoms (hot flashes, night sweats)

  • First-line treatment for moderate to severe symptoms
  • Use lowest effective dose for shortest duration (typically 3-5 years)
  • Reevaluate necessity every 3-6 months 3

• Genitourinary syndrome of menopause

  • Vaginal dryness, atrophy, dyspareunia
  • Consider low-dose vaginal estrogen for localized symptoms (minimal systemic absorption) 4

• Premature or early menopause (before age 45)

  • Recommended to reduce elevated stroke risk 1
  • Continue until at least the average age of natural menopause (around 51) 2

Patient Selection Algorithm

Step 1: Assess for absolute contraindications

• History of hormone-sensitive cancers
• Active liver disease
• Unexplained vaginal bleeding
• History of venous thromboembolism or stroke
• Coronary heart disease 2

Step 2: Consider age and time since menopause

• Ideal candidates:
  • Age <60 years
  • Within 10 years of menopause onset
  • No elevated risk for cardiovascular disease, stroke, or breast cancer 1

Step 3: Evaluate uterine status

• Intact uterus: Requires combined estrogen plus progestogen/progesterone to prevent endometrial cancer 3, 5
• Post-hysterectomy: Estrogen-only therapy is appropriate 3

Step 4: Select appropriate formulation

• Transdermal estradiol: Preferred first-line (lower risk of stroke and VTE) 2
• Oral estrogen: Alternative when transdermal not feasible
• Vaginal estrogen: For isolated genitourinary symptoms 4

Dosing Considerations

• Estrogen:

  • Transdermal: 0.025-0.0375 mg/day patch
  • Oral conjugated estrogen: 0.625 mg/day 2

• Progestogen (for women with intact uterus):

  • Medroxyprogesterone acetate: 2.5 mg/day (continuous)
  • Micronized progesterone: 200 mg for 12-14 days per month (cyclic) 2

Important Risk Considerations

• Combined estrogen/progestogen therapy increases risk of:

  • Breast cancer (with >3-5 years use)
  • Coronary heart disease
  • Stroke
  • Venous thromboembolism 2, 5

• Estrogen-only therapy increases risk of:

  • Stroke
  • Deep vein thrombosis
  • Gallbladder disease 1

Special Populations

Premature/Early Menopause (before age 45)

• HRT strongly recommended until average age of natural menopause
• Benefits typically outweigh risks in this population 1
• For adolescents requiring pubertal induction, gradual dose escalation over 24 months is recommended 1

Women ≥60 years or >10 years post-menopause

• Oral estrogen-containing HRT associated with excess stroke risk
• Benefits rarely outweigh risks in this population 1
• Consider non-hormonal alternatives

Non-Hormonal Alternatives

When HRT is contraindicated or declined, consider:

• SSRIs/SNRIs (venlafaxine preferred)
• Gabapentin
• Clonidine 2, 4

Monitoring

• Initial follow-up at 3 months
• Annual follow-up thereafter
• Assess blood pressure, weight, lipid profile
• Monitor symptom control and bleeding patterns 2

Remember that HRT should be used at the lowest effective dose for the shortest duration necessary to manage symptoms, typically not exceeding 4-5 years due to increasing breast cancer risk with longer duration of use 4, 6.