Research Article| Volume 19, ISSUE 3, P617-627, August 2003

Download started.


The use of estrogen in older women

      The menopause is associated with a relatively abrupt decline in the ovarian production of estrogen that results in a state of estrogen deficiency. This estrogen deficiency state is associated with an accelerated expression of cardiovascular disease, osteoporosis, urogenital atrophy, dermal aging, an increased expression of colorectal cancer, an alteration in the expression of breast cancer which results in more malignant forms of the disease, and the loss of neurons from the brain that is associated with a more rapid decline in cognitive function, balance, and an earlier expression of Alzheimer's disease. Macular degeneration and cataract formation may be additional consequences of the estrogen deficiency state. Thus the estrogen deficiency state may be characterized as a state of accelerated aging. The abrupt transition from the reproductive state of multiple estrogen-dependent neural systems within the brain may affect their function as manifested by the typical menopausal symptoms of hot flashes, mood changes, sleep disturbance, and cognitive impairment. This transition may trigger a cascade of events that contributes to the acceleration of brain aging and the expression of neurodegenerative processes as Alzheimer's disease. This article discusses the use of estrogen to prevent these age-related changes (Box 1).

      The age-related consequences of the estrogen deficiency state

      • Osteoporosis
      • Acceleration of cardiovascular disease
      • Accelerated aging of the skin
      • Increased expression of colon cancer
      • Accelerated decline in cognitive function
      • Accelerated expression of Alzheimer's disease
      • Expression of more malignant forms of breast cancer
      • Tooth loss
      • Cataract formation
      • Macular degeneration
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.


      Subscribe to Clinics in Geriatric Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Bachmann G.A
        Vulvovaginal complaints in treatment of the postmenopausal woman: basic and clinical aspects.
        in: Lobo R.A Treatment of the Postmenopausal Woman. Raven Press, New York1994: 137-142
        • Raz R
        • Stamm W.E
        A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections.
        N Engl J Med. 1993; 329: 753-756
        • Kudenchuk P
        • Maynard C
        • Martin J
        • et al.
        Comparison of presentation, treatment, and outcome of acute myocardial infarction in men versus women (The Myocardial Infarction Triage and Intervention Registry).
        Am J Cardiol. 1996; 78: 9-14
        • Hodis H
        • Mack W
        • Lobo R.A
        Estrogen in the Prevention of Atherosclerosis Trial Research Group.
        Ann Intern Med. 2001; 135: 939-953
        • O'Connor G
        • Morton J
        • Diel M
        • et al.
        • for the Northern New England Cardiovascular Disease Study Group
        Differences between men and women in hospital mortality associated with coronary artery bypass graft surgery.
        Circulation. 1993; 88: 2104-2110
        • Honjo H
        • Ogino Y
        • Naitoh K
        • et al.
        In vivo effects by estrone sulfate on the central nervous system - senile dementia (Alzheimer's type).
        J Steroid Biochem Mole Biol. 1989; 34: 521-525
        • Grady D
        • Rubin S
        • Petitti D.B
        • et al.
        Hormone therapy to prevent disease and prolong life in postmenopausal women.
        Ann Intern Med. 1992; 177: 1016-1037
        • The Writing Group for the PEPI Trial
        Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women.
        JAMA. 1995; 273: 199-208
        • Mueke A
        • Seeger H
        • Lippert T.H
        Estradiol inhibits LDL oxidation: do the progestins medroxyprogesterone acetate and norethindrone acetate influence this effect?.
        Clin Obstet Gyn. 1998; 25: 26-28
        • Zhu X
        • Bonet B
        • Knopp R
        Estradiol 17 beta inhibition of LDL oxidation and endothelial cell cytotoxicity is opposed by progestins to different degrees.
        Atherosclerosis. 2000; 148: 31-41
        • Ross R
        Atherosclerosis - an inflammatory disease.
        N Engl J Med. 1999; 340: 115-126
        • Rosselli M
        • Imthurn B
        • Keller P
        • et al.
        Circulating nitric oxide (nitrate/nitrite) levels in postmenopausal women substituted with 17beta-estradiol and norethistrone acetate.
        Hypertension. 1995; 25: 848-853
        • Sorensen K
        • Dorup I
        • Hermann A
        • et al.
        Combined hormone replacement therapy does not protect women against the age-related decline in endothelium dependent vasomotor function.
        Circulation. 1998; 97: 1234-1238
        • McCrohon J
        • Adams M.R
        • McCredie R
        • et al.
        Hormone replacement therapy is associated with improved arterial physiology in healthy post-menopausal women.
        Clin Endocrin. 1996; 45: 435-441
        • Hulley S
        • Grady D
        • Busch T
        • et al.
        Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group.
        JAMA. 1998; 280: 605-613
        • 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: 321-333
        • Mikkola T
        • Clarkson T
        Estrogen replacement therapy, atherosclerosis, and vascular function.
        Cardiovasc Res. 2002; 53: 605-619
        • Lindsay R
        • Tohme J
        Estrogen treatment of patients with established postmenopausal osteoporosis.
        Am J Obstet Gynecol. 1990; 76: 290-295
        • Recker R
        • Davies K
        • Dowd R
        • et al.
        The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women: a randomized, controlled trial.
        Ann Intern Med. 1997; 130: 897-904
        • Keil D
        • Felson D.T
        • Anderson J
        • et al.
        Hip fracture and the use of estrogens in postmenopausal women. The Framingham Study.
        N Engl J Med. 1987; 317: 1169-1174
        • Ettinger B
        • Black D.M
        • Mitlak B.H
        • et al.
        Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. Results from a 3-year randomized clinical trial.
        JAMA. 1999; 282: 637-689
        • Fisher B
        • Dignam J
        • Bryant J
        • et al.
        Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor positive tumors.
        J Natl Cancer Inst. 1997; 88: 1529-1542
        • Shah M
        • Maibach H
        Estrogen and skin. An overview.
        Am J Clin Dermatol. 2001; 2: 143-150
        • Ashcroft G
        • Greenwell-Wild T
        • Horan M
        • et al.
        Topical estrogen accelerates cutaneous wound healing in aged humans associated with an altered inflammatory response.
        Am J Pathol. 1999; 155: 1137-1146
        • Newcomb P.A
        • Storer B
        Postmenopausal hormone use and risk of large bowel cancer.
        J Nat Cancer Inst. 1995; 87: 1067-1071
        • Kampman E
        • Potter J
        • Slattery M
        • et al.
        Hormone replacement therapy, reproductive history and colon cancer.
        Cancer Causes Control. 1997; 8: 146-158
        • Newcomb P.A
        • Solomon C
        • White E
        Tamoxifen and risk of large bowel cancer in women with breast cancer.
        Breast Can Res Treat. 1999; 53: 271-277
        • CGHFBC. (Collaborative Group on Hormonal Factors in Breast Cancer)
        Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer.
        Lancet. 1997; 350: 1047-1059
        • Ross R.K
        • Paganini-Hill A
        • Wan P.C
        • et al.
        Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin.
        J Nat Cancer Inst. 2000; 92: 328-332
        • Schairer C
        • Lubin J
        • Troisi R
        • et al.
        Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk.
        JAMA. 2000; 283: 485-491
        • Magnusson C
        • Baron J.A
        • Correia N
        • et al.
        Breast-cancer risk following long-term oestrogen- and oestrogen-progestin-replacement therapy.
        Int J Cancer. 1999; 81: 339-344
        • Schairer C
        • Gail M
        • Byrne C
        • et al.
        Estrogen replacement therapy and breast cancer survival in a large screening study.
        J Nat Cancer Inst. 1999; 91: 264-270
        • Grodstein F
        • Stampfer M.J
        • Colditz G.A
        • et al.
        Postmenopausal hormone therapy and mortality.
        N Engl J Med. 1997; 336: 1769-1775
        • Persson I
        • Yuen J
        • Bergkvist L
        • et al.
        Cancer incidence and mortality in women receiving estrogen and estrogen-progestin replacement therapy: a long-term follow-up for a Swedish cohort.
        Int J Cancer. 1996; 67: 327-332
        • Willis D.B
        • Calle E.E
        • Miracle-McMahill H.L
        • et al.
        Estrogen replacement therapy and risk of fatal breast cancer in a prospective cohort of postmenopausal women in the United States.
        Cancer Causes Control. 1996; 7: 449-457
        • Bergkvist L
        • Adami H.O
        • Persson I
        • et al.
        Prognosis after breast cancer diagnosis in women exposed to estrogen and estrogen-progestogen replacement therapy.
        Am J Epidemiol. 1989; 130: 221-228
        • Ross R.K
        • Paganini-Hill A
        • Wan P.C
        • et al.
        Effect of hormone replacement therapy on breast cancer risk: estrogen plus progestin.
        J Nat Cancer Inst. 2000; 92: 328-332
        • O'Meara E
        • Rossing M
        • Daling J.R
        • et al.
        Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality.
        J Nat Cancer Inst. 2001; 93: 754-761
        • Murphy D.C
        • DeCarli C
        • McIntosh A.R
        Sex differences in human brain morphometry and metabolism: an in vivo quantitative magnetic resonance imaging and position emission tomography study on the effect of aging.
        Arch Geriatr Psych. 1996; 53: 585-594
        • Maki P
        • Zonderman A
        • Resnick S
        Enhanced verbal memory in nondemented elderly women receiving hormone-replacement therapy.
        Am J Psychiatry. 2001; 158: 1227-1233
        • Yaffe K
        • Lui L.Y
        • Grady D
        • et al.
        Cognitive decline in women in relation to non-protein-bound oestradiol concentrations.
        Lancet. 2000; 356: 694-695
        • Rice M.M
        • Graves A.B
        • McCurry S.M
        • et al.
        Postmenopausal estrogen and estrogen-progestin use and 2-year rate of cognitive change in a cohort of older Japanese American women.
        Arch Int Med. 2000; 160: 1641-1649
        • Naessen T
        • Lindmark B
        • Larsen H.C
        Better postural balance in elderly women receiving estrogens.
        Am J Obstet Gynecol. 1997; 177: 412-416
        • Berlinger W.G
        • Potter J.F
        Low body mass index in demented outpatients.
        JAGS. 1991; 39: 973-978
        • Ball L.J
        • Mandi D
        • Birge S.J
        Validation of a mailed health survey for screening dementia of the Alzheimer's type.
        J Am Ger Soc. 2001; 49: 798-802
        • Yaffe K
        • Browner W
        • Cauley J
        • et al.
        Association between bone mineral density and cognitive decline in older women.
        JAGS. 1999; 47: 1176-1182
        • Tang M.X
        • Jacobs D
        • Stern Y
        • et al.
        Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease.
        Lancet. 1996; 348: 429-432
        • Birge S.J
        Estrogen and the brain: implications for menopause management.
        in: Schneider H.P.G Menopause: the state of the art–in research and management. Pantheon Publishing, London2002: 191-195
        • Mathews K
        • Cauley J
        • Yaffe K
        • et al.
        Estrogen replacement therapy and cognitive decline in older women.
        JAGS. 1999; 47: 518-523
        • Zandi P.P
        • Carlson M.C
        • Plassman B.L
        • et al.
        Hormone replacement therapy and incidence of Alzheimer's disease in older women. The Cache County Study.
        JAMA. 2002; 288: 2123-2129
        • Mulnard R.A
        • Cotman C.W
        • Kawas C
        • et al.
        Estrogen replacement therapy for treatment of mild to moderate Alzheimer's disease: A 1-year randomized controlled trial.
        JAMA. 2000; 283: 1054-1055
        • Grodstein F
        • Manson J.E
        • Colditz G.A
        • et al.
        A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease.
        Ann Intern Med. 2000; 133: 933-941
        • Williams D.B
        • Voigt B
        • Fu Y
        • et al.
        Assessment of less than monthly progestin therapy in postmenopausal women given estrogen replacement.
        Obstet Gynecol. 1994; 84: 787-793
        • Naftolin F
        • Silver D
        Is progestogen supplementation of ERT really necessary?.
        Menopause. 2002; 9: 1-2