What are the potential risks and considerations to watch out for when initiating Hormone Replacement Therapy (HRT)?

Key Risks and Considerations for Hormone Replacement Therapy (HRT)

HRT should not be routinely used for prevention of chronic conditions in postmenopausal women as the harmful effects are likely to exceed the chronic disease prevention benefits for most women. 1, 2

Cardiovascular and Thrombotic Risks

• For every 10,000 women taking estrogen and progestin for 1 year, there may be 7 additional coronary heart disease (CHD) events, 8 more strokes, and 8 more pulmonary emboli 3, 1
• Risk of venous thromboembolism (VTE) is 2-fold higher with estrogen plus progestin therapy compared to placebo, with increased risk demonstrated during the first year of use 4
• Women should be informed that cardiovascular risks (VTE, CHD, stroke) can occur within the first 1-2 years of therapy 5, 4
• Transdermal routes of HRT administration should be preferred as they have less impact on coagulation 1
• HRT should be discontinued at least 4-6 weeks before surgeries associated with increased thromboembolism risk or during periods of prolonged immobilization 4

Cancer Risks

Breast Cancer

• Combined estrogen-progestin therapy is associated with 8 more invasive breast cancers per 10,000 women-years 3, 4
• Long-term use of estrogen alone (≥20 years) is associated with increased breast cancer risk (relative risk 1.42) 2
• Risk of breast cancer appears to increase with longer-term HRT use and returns to baseline about 5 years after stopping treatment 4

Endometrial Cancer

• Unopposed estrogen (without progestin) in women with an intact uterus increases endometrial cancer risk 2-12 fold 4
• The greatest risk appears with prolonged use (15-24 fold increased risk for 5-10 years of use) and persists for 8-15 years after discontinuation 4
• Women with an intact uterus must use combination estrogen and progestin therapy to reduce endometrial cancer risk by approximately 90% 1

Ovarian Cancer

• The WHI estrogen plus progestin substudy showed a non-significant increased risk of ovarian cancer (relative risk 1.58) 4
• Some epidemiologic studies associate HRT use for 5+ years with increased ovarian cancer risk, though findings are inconsistent 4

Other Health Risks

• Increased risk of gallbladder disease, particularly with oral HRT formulations 1, 5
• Increased risk of urinary incontinence 5
• Possible increased risk of dementia in women starting HRT after age 65 4

Potential Benefits

• Reduced vasomotor symptoms (hot flashes) by approximately 75% 1
• Improved genitourinary symptoms with low-dose vaginal estrogen preparations (60-80% improvement) 1
• Reduced risk of osteoporosis and fractures (5 fewer hip fractures per 10,000 women-years) 3, 2
• Reduced risk of colorectal cancer (6 fewer cases per 10,000 women-years) with combined therapy 3, 2

Risk-Benefit Considerations Based on Timing

• The benefit-risk profile is most favorable for women under 60 years of age or within 10 years of menopause onset 1, 2
• For women who are many years past menopause (>10 years) or over 60 years old, the harmful effects are more likely to exceed benefits 1, 2
• Women starting HRT more than 10 years after menopause have increased probability of harm 2

Absolute Contraindications to HRT

• History of breast cancer 1
• Coronary heart disease 1
• Previous venous thromboembolic event or stroke 1
• Active liver disease 1
• Antiphospholipid syndrome 1
• Hormone-sensitive cancers 1

Recommendations for HRT Use

• HRT should be used primarily for management of menopausal symptoms rather than prevention of chronic conditions 3, 1
• Use the lowest effective dose for the shortest possible time 3, 1, 5
• For women with an intact uterus, combination estrogen and progestin therapy is required 1
• For women without a uterus, estrogen-alone therapy can be used 1
• For women with genitourinary symptoms only, consider low-dose vaginal estrogen preparations with minimal systemic absorption 1, 2

Monitoring Recommendations

• All women using HRT should receive yearly breast examinations and perform monthly breast self-examinations 4
• Schedule mammography examinations based on age, risk factors, and prior mammogram results 4
• Clinical surveillance for abnormal genital bleeding is important; adequate diagnostic measures should be undertaken to rule out malignancy 4