Chap. 29 Menopause (2) Hormone Replacement Therapy

Estrogen deficiency –Physiologic –Genetically programed Postmenopausal women 의 20% 미만에서 HRT 를 시행. Although estrogen replacement Tx is not completely risk-free, health benefits appears to outweigh risk.

Ix. & CIx. For ERT

Benefits Hot flashes Osteoporosis Cardiovascular disease

Hot flashes Relief of hot flashes – 대부분의 여성에게 있어서 HRT 를 시작하고 유 지하는 most common reason 이다. Insomnia, 집중력 약화 유발 대부분 ERT 를 시작한 수 일안에 증상 완화 몇몇 경우에서는 수 주가 걸리기도 함.

Osteoporosis HRT 는 bone mass, skeletal integrity 의 유 지에 도움을 준다. -> osteoporosis 를 예방하는 효과 Estrogen – 장의 Ca 흡수 촉진, 신장의 Ca 보존 증가. –Direct 하게 Osteoclast function –Bone loss 를 느리게 만듦. ERT should be initiated at menopause and given for a long time

progesterone promotes bone formation by –directly, increasing osteoblast activity –indirectly, by inhibiting glucocorticoid effect on osteoblast progestine 단독 사용은 불가.

Cardiovascular disease protects against cardiovascular disease (coronary a. ds. & stroke) –decrease risk of both MI & stroke by 50% Mechanism –effects on serum lipid and lipoprotein low-density lipoprotein↓ high-density lipoprotein↑ total cholesterol↓ HDL/ LDL ↑ –these effects are attenuated by concomitant progestin use & by time

anti-atherosclerosis effect on blood vessels –direct effect on blood vessels that is not reversed by progestin –antioxidants that decreases formation of lipid peroxidases --> minimizing oxidation of low-density lipoprotein cholesterol --> decrease atheroscrelosis vasodilation –direct effect on blood vessel endothelial cells --> immediate vasodilation

effect on coagulation –low doses of estrogen(0.625mg daily of conjugated estrogen) results in subclinical decrease in coagulability by decreasing platelet aggregation & fibrinogen and by inhibiting plasminogen formation → long-term therapy 에 사용 –higher dose of estrogen (i.e. 1.25mg of conjugated estrogen or does equivalent to OC's) -> increase in coagulability

Potential Health Risks risks of estrogen therapy appear to be dose-related

Breast cancer –controversial Endometrial cancer –women used estrogen alone were 4-7times more likely to develop endometrial Ca. → simultaneous use of progestines effectively prevents this problem – endometrial evaluation for all women with irregular vaginal bleeding Gallbladder Disease –symptomatic gallbladder disease 의 risk↑(2 배 )

Thrombophlebitis –no increased risk of thrombophlebitis, despite well-established association with use of OC –women who have a Hx. of thrombophlebitis should be offered estrogen Tx. Hypertension –relative CIx. to OC because higher-dose formulations further increase BP. –dose of conjugated estrogens used for ERT have little effect on BP.

Side effect –vaginal bleeding any vaginal bleeding may be distressing –hormonal replacement regimens associated with amenorrhea are preferable daily use of estrogen & cyclic progestin → cyclic bleeding in most women daily use of estrogen & progestin in an effort to avoid cyclic bleeding after several months, daily progestin Tx will result in amenorrhea in more than 1/2 of women with minimal risk of hyperplasia

–endometrial biopsy irregular bleeding may be an early sign of endometrial hyperplasia or malignancy indicated because of known association of ERT with endometrial neoplasia. breast tenderness –both estrogen and progesterone stimulation of breast tissue –fibrocystic breast change –Relieve breast Sx. decrease daily estrogen dose to equivalent of 0.625mg of conjugated equine estrogen reduce progestin to equivalent of 2.5mg of medroxyprogesterone

mood changes –progestins are known to cause anxiety, irritability or depression weigh gain and water retention

Special Cases History of breast cancer –limited date suggest no increased risk of breast cancer but, esrtrogen should be used with caution –nonmetastatic(node-negative) ER(-) breast cancer, and strong F.Hx. of osteoporosis & heart disease particularly,  benifits of estrogen may outweigh low theoretic risk that hormone will predispose her to development of recurrent cancer

History of Endometrial cancer –theoretically, estrogen & progesterone should not increase risk of recurrent endometrial cancer; Endometriosis –recurrent endometriosis or malignant transformation of endometriosis in women with endometriosis who take ERT following bilateral oophorectomy reported.

Liver Disease –estrogens are metabolized in liver –normal dose of conjugated estrogens could lead to a higher level of circulating estrogens than expected --> avoided in women with active or chronic liver disease