What are the considerations for Hormone Replacement Therapy (HRT) in a patient with a history of endometriosis?

Hormone Replacement Therapy in Patients with a History of Endometriosis

For women with a history of endometriosis who require hormone replacement therapy, combined estrogen/progestogen therapy is recommended rather than estrogen-only therapy, even after hysterectomy, to reduce the risk of disease reactivation. 1

Risk Assessment and General Considerations

• Endometriosis is generally considered an estrogen-dependent disease, but it can affect up to 2.2% of postmenopausal women 2
• Women with endometriosis often experience premature menopause due to bilateral oophorectomy or repeated ovarian surgeries, making HRT particularly important for their health 3
• These women have higher background risk of cardiovascular disorders, hypercholesterolemia, and decreased bone mineral density due to previous treatments (GnRH agonists, progestins) 3

HRT Recommendations Based on Surgical Status

For women with endometriosis who underwent oophorectomy:

• Combined estrogen/progestogen therapy is effective for vasomotor symptoms and may reduce the risk of disease reactivation 1
• HRT should be continued at least until the average age of natural menopause to prevent long-term health consequences 1
• Estrogen-only HRT should be avoided even after hysterectomy due to risk of disease reactivation 3

For women with intact uterus:

• Combined HRT schemes are mandatory to protect the endometrium 1
• Continuous or cyclic combined preparations are preferred over sequential regimens 2

Medication Options

• 17-beta estradiol is preferred to ethinylestradiol or conjugated equine estrogens for estrogen replacement 1
• For progestogen component, options include:
  • Micronized natural progesterone (200 mg/day) 4
  • Medroxyprogesterone acetate (10 mg per day for 12 days per month) 4
  • Dydrogesterone (5-10 mg/day) 1
• Tibolone (2.5 mg/day) is an alternative option with potentially lower risk of endometriosis recurrence 2, 5
• For hypertensive women with endometriosis history, transdermal estradiol is the preferred delivery method 1

Monitoring and Risks

• Annual clinical review is recommended, paying particular attention to compliance 1
• Monitor for potential recurrence of endometriosis symptoms, which may include pelvic pain or dyspareunia 4
• The absolute risk of disease recurrence and malignant transformation cannot be precisely quantified based on current evidence 6
• Some case reports suggest increased risk of malignant transformation of endometriomas in patients using unopposed estrogen HRT 2

Special Considerations

• For women with BRCA1/2 mutations but without personal history of breast cancer after prophylactic bilateral salpingo-oophorectomy, HRT remains a treatment option 1
• HRT is generally contraindicated in breast cancer survivors 1
• For women with endometriosis and migraine, HRT should not be considered contraindicated, but consider changing dose, route of administration or regimen if migraine worsens during treatment 1

Common Pitfalls to Avoid

• Avoid prescribing estrogen-only HRT even after hysterectomy, as this appears to carry a higher risk of endometriosis recurrence than combined preparations 5
• Don't delay starting HRT after surgical menopause, as this does not provide any benefit in reducing recurrence risk 5
• Don't withhold HRT from symptomatic women solely due to their history of endometriosis, as the benefits often outweigh the theoretical risks 2