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Toronto Notes 2019
Menopause
Gynecology GY35
Side Effects of HRT
• abnormaluterinebleeding
• mastodynia:breasttenderness
• edema, bloating, heartburn, nausea
• moodchanges(progesterone)
• canbeworseinprogesteronephaseofcombinedtherapy
Contraindications to HRT
• absolute
■ acute liver disease
■ undiagnosed vaginal bleeding
■ history of breast cancer
■ known or suspected uterine cancer/breast cancer
■ acute vascular thrombosis or history of severe thrombophlebitis or thromboembolic disease ■ cardiovascular disease
• relative
■ pre-existing uncontrolled HTN
■ uterine fibroids and endometriosis
■ familial hyperlipidemias
■ migraine headaches
■ family history of estrogen-dependent cancer
■ chronic thrombophlebitis
■ DM(withvasculardisease)
■ gallbladder disease, hypertriglyceridemia, impaired liver function (consider transdermal estrogen) ■ fibrocystic disease of the breasts
WOMEN’S HEALTH INITIATIVE (launched in 1991)
• twonon-randomizedstudiesinvestigatinghealthrisksandbenefitsofHRTinhealthypostmenopausal women 50-79 yr old
■ continuous combined HRT (CEE 0.625 mg + MPA 2.5 mg OD) in 16,608 women with an intact uterus
■ estrogen-alone (CEE 0.625 mg) in 10,739 women with a previous hysterectomy
• botharmsofthetrialwerestoppedearlybecauseofevidenceofincreasedriskofbreastcancer,stroke,
PE, and CHD in the combined HRT arm, and increased risk of stroke with no CHD benefits in the
estrogen-alone arm
• theapparentincreaseinCHDwasindisagreementwithresultsofpreviousobservationaltrial
• resultsoftheWHIstudyhavesincebeenchallengedandrevisionofhowCHDwasdiagnosedledto
loss of statistical significance of the results
• benefits and risks reported as number of cases per 10,000 women each year
Absolute Contraindications to HRT
ABCD
Acute liver disease
Undiagnosed vaginal Bleeding
Cancer (breast/uterine), Cardiovascular disease
DVT (thromboembolic disease)
Table 18. HRT Benefits vs. Risks
Benefits
Vasomotor Symptoms: less frequent and severe with
use of either combined or estrogen-alone HRT
Osteoporosis: 5 fewer cases of hip fractures and 47 fewer cases of all fractures with combined HRT; 6 fewer cases of hip fractures with estrogen alone
Colon Cancer: 6 fewer cases with combined HRT (WHI) One additional case with estrogen-alone
Risks
Stroke: 8 additional cases with combined HRT and 12 additional cases
for estrogen alone (WHI)
DVT/PE: 18 additional cases with combined HRT and 9 additional cases for estrogen-alone (WHI)
CHD: 7 additional MIs with combined HRT (WHI); secondary analysis suggests greater absolute risk for women aged >70 yr and for women who start HRT >10 yr post-menopause
Breast Cancer: 8 additional cases with combined HRT (WHI) Risk only increased after >5 yr of combined HRT use; no increased risk for estrogen-alone
Dementia and Mild Cognitive Impairment: 50% greater risk of developing dementia in women taking estrogen-alone after age 65; risk is greater for women taking combined HRT; risk of developing dementia was reduced for women taking HRT before age 65
Long-Term Hormone Therapy for Perimenopausal and Postmenopausal Women
Cochrane DB Syst Rev 2012;7:CD004143
Purpose: To determine the effect of long-term HRT on mortality, cardiovascular outcomes, cancer, gallbladder disease, fractures, cognition, and QOL in perimenopausal and postmenopausal women, during HRT use, and after cessation of HRT. Results: 23 studies with 42,380 women included. 70% of the data from the WHI (1998) and
HERS (1998). None of the studies focused on perimenopausal women. Combined continuous HRT: increased risk of coronary event after 1
yr (absolute risk 18/1,000, 95% CI 3-7), venous thromboembolism after 1 yr (AR 7/1,000, 95% CI 4-11), stroke after 3 yr (AR 18/1,000, 95% CI 14-23), breast cancer after 5.6 yr (AR 23/1,000, 95% CI 19- 29), gallbladder disease after 5.6 yr (AR 27/1,000, 95% CI 21-34), and death from lung cancer after
5.6 yr use (AR 9/1,000, 95% CI 6-13). Estrogen only HRT: increased risk of venous thromboembolism after 1-2 yr use (AR 5/1,000, 95% CI 2-10; after 7 yr AR 21/1,000, 95% CI 16-28), stroke after 7 yr (AR 32/1,000, 95% CI 25-40), and gallbladder disease after 7 yr use (AR 45/1,000, 95% CI 36-57) and did not significantly affect the risk of breast cancer. Women >65 yr of age taking combined HRT had
a statistically significant increase in the incidence of dementia after 4 yr use (AR 18/1,000, 95% CI 11-30). Women taking HRT had a decreased risk
of fractures with combined HRT after 5.6 yr (AR 86/1,000, 95% CI 79-84) and 7.1 yr of estrogen only HRT (AR 102/1,000, 95% CI 91-112).
Conclusions: HRT is not indicated for primary or secondary prevention of cardiovascular disease or dementia. Although HRT is considered effective for the prevention of postmenopausal osteoporosis,
it is generally recommended as an option only for women at significant risk, for whom non-estrogen therapies are unsuitable.