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Estrogen Replacement
Aka: Estrogen Replacement, Hormone Replacement, Estrogen Replacement Therapy, Hormone Replacement Therapy- Indications
- See Also
- General
- Different Estrogen types are equivalent in efficacy
- Adverse effects and safety are also equivalent
- Nelson (2004) JAMA 291:1610-20
- Different Estrogen types are equivalent in efficacy
- Advantages: Benefits of Estrogen Replacement
- Osteoporosis
- Estrogen increases bone density by 20-30%
- Increases Bone Mineral Density 5-15% in 3 years
- Benefit even if started late postmenopausal
- Benefit also seen with Transdermal Estrogen
- Hazard Ratio for Hip Fracture: 0.66
- (2002) JAMA 288:321-333
- Endocrine Effects
- Reduces Type II Diabetes Mellitus Risk by 20% (PEPI)
- Improves Glucose Metabolism
- Improves Insulin sensitivity
- Decreases fasting Glucose levels
- Relief of perimenopausal Major Depression symptoms
- Relief of Genitourinary symptoms
- See adverse effects below regarding Incontinence
- Vaginal Dryness
- Dyspareunia
- Urethritis
- Relief of perimenonpausal vasomotor symptoms
- Hot Flashes
- Insomnia
- Irritability
- Anxiety
- Reduces tooth loss
- Protective against Colorectal Cancer
- Decreases cumulative Colon Cancer risk
- Hazard ratio for Colorectal Cancer 0.63
- (2002) JAMA 288:321-333
- Osteoporosis
- Disadvantages: Mixed Risks and Benefits
- Cardiovascular disease
- NIH Women's Health Initiative Results
- Combined HRT Study stopped early
- Increased coronary risk by 7 per 10,000 patients
- Hazard ratio for coronary events: 1.29
- Slight risk, but definately no CAD benefit
- Estrogen alone post-Hysterectomy
- This arm of study continues
- References
- Combined HRT Study stopped early
- Earlier studies questioned cardiovascular benefit
- Increased coronary event risk in first year of ERT
- Protective effect after first year
- Grodstein (2001) Ann Intern Med 135:1-8
- Herrington (2001) N Engl J Med 343:522-9
- Improved survival in Congestive Heart Failure
- Lowers systolic Blood Pressure (no diastolic effect)
- More pronounced effect in Obesity and advanced age
- Scuteri (2001) Ann Intern Med 135:229-38
- Lipid effects (Estrogen alone without Prosterone)
- Increases HDL
- Decreases LDL
- NIH Women's Health Initiative Results
- Cerebrovascular Disease Risk
- Initial studies showed increased CVA risk
- NIH Women's Health Initiative also had increased risk
- Increased Incidence by 8 per 10,000 patients
- Hazard ratio for Cerebrovascular Accident: 1.41
- (2002) JAMA 288:321-333
- Large prospective cohort study with no increased risk
- No HRT increased ischemic or Hemorrhagic CVA risk
- Angeja (2001) J Am Coll Cardiol 38:1297-301
- Cognitive effects
- Initial studies showed decreased Alzheimer's Risk
- Appeared to protect against cognitive decline
- Paganini (1996) Arch Intern Med 156:2213-7
- Yaffe (2000) Lancet 356:708-12
- Recent studies have shown no benefit
- No benefit
- May adversely affect global cognitive function
- Initial studies showed decreased Alzheimer's Risk
- Cardiovascular disease
- Disadvantages: Risks of Estrogen Replacement
- Breast Cancer
- See Breast Cancer Risk Factors
- Risk appears to be associated with replacement type
- Associated with Continuous Estrogen Replacement
- Less associated with Estrogen alone
- Less associated with Sequential Replacement
- Weiss (2002) Obstet Gynecol 100:1148-58
- Combination therapy increases risk
- Estrogen only therapy: 3-7 additional cases/1000
- Combination therapy: 18-20 additional cases/1000
- (2003) Lancet 362:419-27
- Lytinen (2006) Obstet Gynecol 108:1354-60
- Associated with Continuous Estrogen Replacement
- Endometrial Cancer
- Occurs with Unopposed Estrogen (without Progesterone)
- Atypical Hyperplasia in 30% on Unopposed Estrogen
- Risk remains 10 years after Unopposed Estrogen use
- Women with intact Uterus must use combination HRT
- Evaluate Postmenopausal Abnormal Uterine Bleeding
- Anticipate uterine bleeding for first 4-6 months
- Evaluate bleeding >6 months after starting HRT
- Endometrial Biopsy
- Uterine Ultrasound
- Occurs with Unopposed Estrogen (without Progesterone)
- Ovarian Cancer
- Associated with Estrogen use without Progestin
- Relative risk of Ovarian Cancer in ERT: 1.6
- Relative risk if ERT use >20 years: 3.2
- Lacey (2002) JAMA 288:334-41
- Venous Thrombosis risk
- Higher risk with Estrogen dose over 2.5 mg/day
- Higher risk when used with Progesterone
- NIH Women's Initiative
- Hazard Ratio for Pulmonary Embolism: 2.13
- (2002) JAMA 288:321-333
- Risk if prior Venous thrombosis occurred
- Trauma-related: no increased risk
- Oral Contraceptive related: possible increased risk
- Esterified Estrogen (Menest) not assoc. with thrombus
- May be preferred form for Estrogen Replacement
- Smith (2004) JAMA 292:1581-7
- Genitourinary
- Special considerations
- Gall Bladder disease risk
- Relative risk: 1.5 to 2.0
- Risk persists for 5 years after Estrogen stopped
- Increased Triglycerides
- Baseline Triglycerides: 250 to 750
- Start Estrogen Replacement
- Recheck Triglycerides in 4 weeks
- Baseline Triglycerides: over 500
- Consider transdermal Estrogen Replacement
- Baseline Triglycerides: over 750
- Avoid Estrogen Replacement
- Risk of Pancreatitis
- Baseline Triglycerides: 250 to 750
- Gall Bladder disease risk
- Breast Cancer
- Contraindications: Estrogen Replacement
- Absolute
- Unexplained Vaginal Bleeding
- Acute liver disease
- Breast Cancer
- Active Thrombophlebitis
- Thromboembolic disorder including past history of Venous Thromboembolism
- Pregnancy
- Relative
- Chronic Liver Disease
- Heart disease
- Endometrial Cancer
- Hypertension
- Familial Hyperlipidemia
- Consider Transdermal Estrogen
- Seizure disorder
- Migraine Headaches
- History of Thrombophlebitis
- Endometriosis
- Gall Bladder disease
- Absolute
- Safety
- Recent data suggests HRT is safe for 4-5 years of use
- NIH Women's Health Initiative did not study age <50
- Consider continuing Estrogen in these patients
- (2002) JAMA 288:321-333
- Meta-analysis 4000 patients, 29 studies
- Initially irregular bleeding for 6 months
- Amenorrhea in 75% after 6 months
- Atrophic Endometrium in 90% of patients
- Endometrial Hyperplasia in 1% of patients
- Adenocarcinoma in 0.05% of patients (2 cases)
- Udoff (1995) Obstet Gynecol 86:306-16
- Preparations
- Management: Algorithm for choice of replacement method
- Use the lowest effective dose of replacement that controls symptoms
- Age under 40 years, Ovaries removed, or Perimenopause
- Menopause
- Late Postmenopausal
- Continuous Estrogen Replacement OR
- Vaginal Estrogen for atrophic vagina
- Management: Protocol to stop Hormone Replacement
- Timing of Estrogen Replacement discontinuation
- Premature Menopause
- Re-evaluate continued Estrogen use at age 51
- Estrogen Replacement with Progesterone
- Consider stopping Estrogen Replacement after 3-5 years of use
- Estrogen Replacement without Progesterone
- Consider stopping Estrogen Replacement after 7 years of use
- Premature Menopause
- Slow taper over 2-3 months reduces withdrawal affects
- Estrogen withdrawal effects to anticipate
- Irregular Vaginal Bleeding or spotting
- Hot Flushes
- Taper
- First: HRT only monday to friday for 1-3 months
- Next: HRT only monday, wednesday, friday x1-3 months
- Timing of Estrogen Replacement discontinuation
- Management: Consider alternatives to Estrogen Replacement
- See Hot Flushes
- See Cardiac Risk Management
- See Osteoporosis Management
- Local Estrogen sources (Vaginal Estrogen)
- Vagifem tablets
- E-String vaginal ring