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1 Climacteric Symptoms & Hormone Therapy Hyoung Moo Park, M.D. Department Of Obstetrics and Gynecology Chung Ang University College of Medicine & Hospital E mail : hmpark@hananet.net Abstract After menopause, estrogen deficiency from the loss of ovarian function results in various symptoms and metabolic changes, which lead to an increased risk of chronic diseases. Troublesome menopausal symptoms, vasomotor and/or psychological, are the first to develop, and various kinds of disorders related to estrogen deficiency such as genitourinary atrophy, involutional osteoporosis, cardiovascular, and Alzheimer's diseases follow. Among these, two major long term consequences of ovarian failure are osteoporosis and cardiovascular disease, which are also the major causes of morbidity, mortality and financial costs. Hormone therapy by using estrogen with or without progesterone, is most consistently effective for the treatment of acute and some intermediate menopause related symptoms such as vasomotor symptoms and vaginal dryness, and therefore has been recommended as the first line measure to prevent and treat the acute symptoms of estrogen deficiency. It also has been reported that hormone therapy reduces the risks of some long term sequelaes, suggesting both therapeutic and preventive roles in postmenopausal women. However, it is clear that hormone therapy is not a panacea and is not suitable for all postmenopausal women because of side effects and some concerns about cancer risks. The rate of long term compliance is also low at present. Recent RCTs showed that hormone therapy does not seem to be effective in improving cognition and preventing CHD and dementia. However, there is a growing consensus that the early initiation of hormone therapy provides protection from CVS and CNS, the two most important areas, whereas RCTs have disagreed with observational data. This means that in young women at early menopause, "a window of therapeutic opportunity" exists for hormone therapy, since treatment during this period may provide cardio and neuroprotection. More studies are urgently needed on this controversy. Current recommendations suggest treatment with the lowest effective dose for the shortest period of time and individualized treatment based on patient s risk and benefit ratio. Keywords : Menopause; Symptom; Sormone; Benefit; Risk; Early initiation 11

2 Short & long term consequences of menopause 2 60~ ~ ~ Incidence of climacteric symptoms in Korean women

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4 Clinical manifestation of hot flush (sensation) (heart rate) 5~35 1~7 0.1~0.9 14

5 Management of hot flushes paced respiration 15

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14 Risk of cognitive impairment & dementia in WHI memory study 95%CI 95%CI ~ ~ ~ ~

15 Risk of invasive breast cancer in WHI 95% ~ ~

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17 ta/025/025menopauseintropostconf.htm. 9. Ockene JK, Barad DH, Cochrane BB. Recurrent vasomotor symptoms common for EPT users in WHI after study was discontinued. JAMA 2005; 294: Pandya KJ, Morrow GR, Roscoe JA. Gabapentin for hot flashes in 420 women with breast cancer: a randomised double blind placebo controlled trial. Lancet 2005; 366: Avis NE, Brambilla D, Mckinlay SM, Vass K. A longitudinal analysis of the association between menopause and depression : Results from the Massachusetts Women s Health Study, Ann Epidemiol 1994; 4: Kessler RC, McGonagle KA, Swartz M, Blazer DG, Nelson CB. Sex and depression in the National Comorbidity Survey I : lifetime prevalence, choronicity and recurrence, J Affective Disorders 1993; 29: Busch CM, Zonderman AB, Costa PT Jr. Menopausal transition and psychological distress in a nationally representative sample: is menopause associated with psychological distress? J Aging Health 1994; 6: Sleep in America Poll. Washington, DC: National Sleep foundation; Accessible at org/2002poll.html 15. Cardozo L, Bachmann G, McClish D, Fonda D, Birgerson L. Meta analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital therapy committee. Obstet Gynecol 1998; 92: Johnson SR, Ettinger B, Macer JL, Ensrud KE, Quan J, Grady D. Uterine and vaginal effects of unopposed Ultralow dose transdermal estradiol. Obstet Gynecol 2005; 105: Fantl JA, Bump RC, Robinson D, McClish DK, Wyman JF. Efficacy of estrogen supplementation in the treatment of urinary incontinence. The continence program for women research group. Obstet Gynecol 1996; 88: Jackson S, Shepherd A, Brookes S, Abrams P. The effect of estrogen supplementation in the treatment of urinary incontinence. ; a double blind placebo controlled trial. Br J Obstet Gynaecol 1999; 106: Grodstein F, Lifford K, Resnick NM, Curhan GC. Postmenopausal hormone therapy and risk of developing urinary incontinence. Obstet Gynecol 2004; 103: Stenmauer JE, Waetgen LE, Vittinghoff E, Subak LL, Hulley SB, Grady D. Postmenopausal Hormone therapy. Dose it cause incontinence? Obstet Gynecol 2005; 106: Hendrix SL, Cochrane BB, Nygaard IE, Handa VL, Barnabei VM, Iglesia C, et al. Effects of estrogen with and without progestin on urinary incontinence. JAMA 2005; 293: Waetjen LE, Brown JS, Vittinghoff E, Ensrud KE, Pinkerton J, Wallace R, et al. The effect on Ultralow dose transdermal estradiol on urinary incontinence in postmenopausal women. Obstet Gynecol 2005; 106: Hulley S, Grady D, Bush T. Randomized trial of estrogen plus progestin for secondary prevention on coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. J Am Med Assoc 1998; 280: Writing Group for the Women s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women s Health Initiative randomized controlled trial. JAMA 2002; 288: Manson JE, Hsia J, Johnson KC. Estrogen plus progestin and 27

18 the risk of coronary heart disease. N Engl J Med 2003; 349: Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hystetectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004; 291: Clarkson TB, Anthony MS, Klein KP. Hormone replacement therapy and coronary artery ahterosclerosis: the monkey model. Br J Obstet Gynaecol 1996; 103(Suppl 13): Clarkson TB, Anthony MS, Morgan TM. Inhibition of postmenopausal atherosclerosis progression : a comparison of the effects of conjugated equine estrogens and soy phytoestrogens. J Clin Endocrinol Metab 2001; 86: Admans MR, Kaplan JR, Manuck SB. Inhibition of coronary artery atherosclerosis by 17 beta estradiol in ovariectomized monkeys. Lack of an effect of added progesterone. Arteriosclerosis 1990; 10: DeKleijin MJJ, Bots ML, BakAAA. Hormone replacement therapy in perimenopausal women and 2 year change of carotid intima media thickness. Maturitas 1999; 32: Hodis HN, Mack WJ, Lobo RA. Estrogen in the prevention of atherosclerosis : a randomized double blind, placebo controlled trial. Ann Int Med 2001; 135: Akhrass F, Evnas AT, Wang Y. Hormone replacement therapy is associated with less coronary atherosclerosis in postmenopausal women. J Clin Endocrinol Metab 2003; 88: Harman SM, Brinton EA, Cedars M, Lobo R, Manson JE, Merriam GR. KEEPS: The Kronos early estrogen prevention study. Climacteric 2005; 8: Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JE, et al. for the WHIMS Investigators. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women s Health Initiative Memory Study: a randomized controlled trial. JAMA 2003; 289: Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ochene JK, et al. for the WHIMS Investigators. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women s Health Initiative Memory Study: a randomized controlled trial. JAMA 2003; 289: Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB. Conjugated equine estrogens and global cognitive function in postmenopausal women. Women's health initiative memory study. JAMA 2004; 291: Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, et al. for the Women s Health Initiative Memory Study Investigators. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women s Health Initiative Memory Study. JAMA 2004: 291: Zandi PP, Carlson MC, Plassman BL, Welsh Bohmer KA, Mayer LS, Steffens DC. Hormone replacement therapy and incidence of Alzheimer disease in older women. The Cache County Study. JAMA 2002; 288: Bagger YZ, Tanko LB, Alexandersen P, Qin G, Christiansen C. (for the PERF Study Group) Early postmenopausal hormone therapy may prevent cognitive impairment later in life. Menopause 2005; 12: Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy : collaborative reanalysis of data from 51 epidemiological studies of 52 28

19 705 women with breast cancer and women without breast cancer. Lancet 1997; 350: Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horwitz RI. A clinical trial of estrogen replacement therapy after ischemic stroke. N Engl J Med 2001; 345: Beral V, Reeves G, Banks E. Current evidence about the effect of hormone replacement therapy on the incidence of major conditions in postmenopausal women. BJOG 2005; 112: , Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Lane GD, Rodabough RJ, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women : the Women's Health Initiative Randomized Trial. JAMA 2003; 289; Hulley S, Furberg C, Barrett connor E, Cauley J, Grady D, Haskell W, et al. Noncardiovascular disease outcomes during replacement study follow up (HERS ), JAMA 2002; 288; de Lignieres B, de Vathaire F, Fournier S, Urbinelli R, Allaert F, Le MG. Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women. Climacteric 2002; 5: Fournier A, Berrino F, Riboli E, Avenel V, Clavel Chapelon F. Breast cancer risk in relation to different types of hormone replacement therapy in the E3N EPIC cohort. Int J Cancer 2005; 114: Von Schoultz E, Rutqvist LE. Menopausal hormone therapy after breast cancer: the Stockholm randomized Trail. J Natl Cancer Inst 2005; 97: Holmberg L, Anderson G. HABITS (hormonal replacement therapy after breast cancer is it safe?) a randomized comparison stopped. Lancet 2004; 363: years of hormone therapy: Heart and estrogen/progestin Peer Reviewer Commentary 29

Treatment and Role of Hormaonal Replaement Therapy

Treatment and Role of Hormaonal Replaement Therapy Treatment and Role of Hormone Replacement Therapy Chung-Ang University Hospital Chee Jeong Kim 7.2 5.3 6.4 5.6 7.3 5.5 1 1 2 3 4 10 11 7 34 49 122 123 1.0 - - 10. 2001 1998 1998 Improvement of postmenopausal