Side Effects of Hormone Replacement Therapy (HRT) to Discuss with Patients
Patients should be informed about the significant risks of HRT including increased risk of breast cancer, venous thromboembolism, stroke, coronary heart disease, and gallbladder disease before starting therapy. 1, 2
Major Risks of HRT
Cardiovascular and Thrombotic Risks
- Venous thromboembolism (VTE): 2-fold increased risk (35 vs 17 per 10,000 women-years) 2
- Deep vein thrombosis risk: 26 vs 13 per 10,000 women-years
- Pulmonary embolism risk: 18 vs 8 per 10,000 women-years
- Risk is highest during the first year of therapy
- Stroke and coronary heart disease: Increased risk, especially when started more than 10 years after menopause 1, 2
- Blood pressure changes: Potential for increased blood pressure 2
Cancer Risks
- Breast cancer: Increased risk with estrogen-progestin combinations (RR 1.24,41 vs 33 cases per 10,000 women-years) 2
- Risk increases with duration of use
- Risk appears to return to baseline about 5 years after stopping treatment
- Women with prior hormone therapy use have higher risk (RR 1.86)
- Endometrial cancer: 2-12 times greater risk with unopposed estrogen in women with intact uterus 2
- Risk increases with duration of treatment and estrogen dose
- Risk persists for 8-15 years after discontinuation
- Ovarian cancer: Potential increased risk, especially with 5+ years of use 2
Gastrointestinal Effects
- Gallbladder disease: 1.8-2.5 times increased risk of cholecystitis 3, 2
- Higher risk with oral formulations
- Risk remains elevated even after stopping HRT
- Nausea and vomiting 2
- Abdominal cramps and bloating 2
Other Physical Side Effects
- Breast tenderness, enlargement, and pain 2
- Irregular vaginal bleeding or spotting (especially during initial months) 2
- Fluid retention and edema 2
- Headaches and migraines 2
- Hair loss 2
- Skin changes: Possible melasma (facial pigmentation) 2
Neurological and Psychological Effects
- Probable dementia: Increased risk in women over 65 2
- Mood disturbances: Depression, irritability, nervousness 2
- Sleep disturbances: Insomnia 2
- Dizziness 2
Factors Affecting Risk Profile
Route of Administration
- Transdermal estrogen has lower risk of VTE compared to oral formulations 3, 1
- Vaginal estrogen for localized symptoms has minimal systemic absorption 1
Formulation Considerations
- Estrogen-only therapy has different risk profile than combined estrogen-progestin therapy 2
- Different progestins have varying side effect profiles 3, 1
Individual Risk Factors
- Age at initiation: Risk-benefit ratio most favorable when started within 10 years of menopause or before age 60 1, 4
- Pre-existing conditions: Diabetes, obesity, and metabolic syndrome increase VTE risk 1
Absolute Contraindications to Discuss
- History of hormone-dependent cancers
- Active liver disease
- History of VTE
- Unexplained vaginal bleeding
- History of stroke or coronary heart disease 1, 5
Monitoring and Follow-up Requirements
- Regular breast examinations and mammograms
- Pelvic examinations
- Blood pressure monitoring
- Periodic reassessment of risks and benefits 1, 2
Important Counseling Points
- HRT should be used at the lowest effective dose for the shortest duration needed 1
- Regular follow-up is essential (8-10 weeks after initiation and annually thereafter) 1
- Attempt to taper to lowest effective dose at 3-6 month intervals 1
- Report any unusual vaginal bleeding immediately 2
- Discontinue HRT 4-6 weeks before surgery with increased thromboembolism risk 2
By thoroughly discussing these potential side effects before initiating HRT, patients can make informed decisions about their treatment and be vigilant about reporting concerning symptoms promptly.