What is the recommended approach to initiate hormone replacement therapy (HRT) in a woman?

Initiating Hormone Replacement Therapy in Women

For women with menopausal symptoms, hormone replacement therapy should be started at the lowest effective dose for the shortest duration necessary, with estradiol as the preferred estrogen and a progestin added for women with an intact uterus. 1, 2, 3

Initial Assessment and Candidate Selection

• Appropriate candidates:

  • Women with moderate to severe vasomotor symptoms
  • Women with vulvovaginal atrophy
  • Women with premature ovarian insufficiency (POI)
  • Women at risk for osteoporosis without contraindications

• Contraindications:

  • History of breast cancer 2
  • Active liver disease 2
  • Recent thromboembolic events 2
  • Unexplained vaginal bleeding 2
  • Women aged 60+ or >10 years post-menopause (increased vascular risks) 2

Medication Selection and Dosing

For Women With an Intact Uterus:

• Must use combined estrogen-progestin therapy to protect the endometrium 1, 3
• Initial regimen options:
  • Oral estradiol 1-2 mg daily + cyclical progestin (e.g., medroxyprogesterone acetate 2.5 mg daily or micronized progesterone 200 mg for 12-14 days per month) 2, 3
  • Transdermal estradiol patch 0.025-0.0375 mg/day + progestin 2

For Women Without a Uterus:

• Estrogen-only therapy is sufficient 3
• Initial regimen options:
  • Oral estradiol 1-2 mg daily 3
  • Transdermal estradiol patch 0.025-0.0375 mg/day 2

Special Considerations:

• For women with hypertension: Transdermal estradiol is preferred over oral administration 1
• For women with POI: 17-β estradiol is preferred over ethinylestradiol or conjugated equine estrogens 1
• For women with endometriosis: Combined estrogen/progestogen therapy is recommended 1

Administration Schedule

• Cyclic regimen: 3 weeks on, 1 week off (may be appropriate for perimenopausal women) 3
• Continuous regimen: Daily administration without breaks (may be preferred for postmenopausal women seeking amenorrhea) 4

Monitoring and Follow-up

1. Initial follow-up: 1-3 months after starting therapy 2

   • Assess symptom control
   • Evaluate side effects
   • Check blood pressure

2. Annual follow-up: 1, 2

   • Clinical review focusing on compliance
   • Monitor blood pressure and weight
   • Assess bleeding patterns (any abnormal bleeding requires investigation)
   • No routine laboratory monitoring is required unless prompted by specific symptoms

3. Duration and tapering:

   • Attempt to discontinue or taper medication at 3-6 month intervals 3
   • For women with POI, consider continuing until the average age of natural menopause 1

Important Considerations and Risks

• Breast cancer risk:

  • Women with POI: HRT has not been found to increase breast cancer risk before the age of natural menopause 1
  • Combined estrogen-progestin therapy carries higher breast cancer risk than estrogen-only therapy 2

• Cardiovascular risk:

  • HRT is not recommended for secondary prevention of coronary events 2
  • Estrogen-only therapy does not reduce CHD risk 1
  • Increased risk of stroke and DVT, particularly in women over 60 2

• Other potential adverse effects:

  • Gallbladder disease 1
  • Urinary incontinence 1
  • Migraine headaches may worsen (consider changing dose, route, or regimen) 1

Non-hormonal Alternatives

For women with contraindications to HRT, consider:

• SSRIs/SNRIs (e.g., venlafaxine)
• Gabapentin
• Clonidine 2

Androgen Therapy

• Consider only after failure of estrogen therapy for persistent symptoms
• Limited data supports use; long-term health effects unclear
• If started, evaluate effect after 3-6 months and limit to 24 months 1