What are the contraindications for Hormone Replacement Therapy (HRT) in women?

Contraindications for Hormone Replacement Therapy in Women

Hormone replacement therapy (HRT) is contraindicated in women with active liver disease, history of breast cancer, coronary heart disease, previous venous thromboembolism or stroke, and positive antiphospholipid antibodies. 1

Absolute Contraindications

Current or Past Medical Conditions

• Active liver disease 1, 2
• History of breast cancer 1
  • HRT is generally contraindicated in breast cancer survivors 3
  • Breast cancer being treated with adjuvant therapies 4
• History of coronary heart disease 1
• Previous venous thromboembolism or stroke 1
• Positive antiphospholipid antibodies 1
• Endometrial stromal sarcoma 5
• Hormone receptor-positive gastric and bladder cancer 5
• Meningioma and glioma 5

Cancer-Related Contraindications

• Low-grade serous epithelial ovarian cancer 3
• Granulosa cell tumors 3
• Certain types of sarcoma (leiomyosarcoma and stromal sarcoma) 3
• Advanced endometrioid uterine adenocarcinoma 3

Relative Contraindications

Cardiovascular Conditions

• Existing cardiovascular disease 4
• Cerebrovascular disease 4
• Hypertension (though not an absolute contraindication for women with POI) 3
  • For hypertensive women with POI, transdermal estradiol is preferred 3

Cancer-Related Relative Contraindications

• Leiomyosarcoma 5
• Certain types of ovarian tumors 5
• Brain tumors 5
• Advanced metastatic malignant melanoma 5
• Lung cancer 5
• Gastric cancer 5
• Bladder cancer 5

Risks Associated with HRT

Cardiovascular Risks

• Venous thromboembolism: Increased risk (RR 2.14), highest in first year of use (RR 3.49) 3
• Stroke: Small increase in incidence (RR 1.12), primarily thromboembolic stroke (RR 1.20) 3
• Coronary heart disease: HRT may increase incidence of CHD 3

Cancer Risks

• Breast cancer: Combined estrogen/progestogen therapy increases risk when used for more than 3-5 years 1
• Endometrial cancer: Unopposed estrogen increases risk (RR 2.3), with risk increasing with duration of use 3
  • Risk remains elevated 5+ years after discontinuation 3
  • Combined estrogen-progestin therapy does not increase risk 3
• Ovarian cancer: Data inconsistent, but some studies show increased risk with 10+ years of use 3

Other Risks

• Cholecystitis: Increased risk 3, 1

Special Considerations

Women with Hysterectomy

• Women without a uterus do not need progestogen; estrogen-only HRT is sufficient 1
• Evidence insufficient to recommend for or against unopposed estrogen for chronic condition prevention in women who have had hysterectomy 3

Women with Gynecologic Cancers

• No evidence to contraindicate HRT for women with cervical, vaginal, or vulvar cancers (non-hormone-dependent tumors) 3
• HRT is an option for women with BRCA1/2 mutations without personal history of breast cancer after prophylactic bilateral salpingo-oophorectomy 3
• For women with endometriosis who required oophorectomy, combined estrogen/progestogen therapy can effectively treat vasomotor symptoms 3

Premature Ovarian Insufficiency (POI)

• Women with POI should be informed that HRT has not been found to increase breast cancer risk before the age of natural menopause 3
• Migraine should not be seen as a contraindication to HRT use by women with POI 3

Clinical Implications

Understanding these contraindications is crucial for safe prescribing of HRT. The decision to use HRT should weigh the benefits for symptom relief against potential risks, with particular attention to the woman's personal and family medical history. For women with absolute contraindications, non-hormonal alternatives for managing menopausal symptoms should be considered.