Postmenopausal estrogen therapy and depressive symptoms in older women Authors
Cite this article as: Whooley, M.A., Grady, D., Cauley, J.A. et al. J GEN INTERN MED (2000) 15: 535. doi:10.1046/j.1525-1497.2000.04029.x
BACKGROUND: Evidence regarding the effect of postmenopausal estrogen therapy on mood is limited.
METHODS: To determine whether postmenopausal estrogen therapy is associated with fewer depressive symptoms in elderly women, we conducted a cross-sectional study of 6,602 white women ages 71 years or older who were recruited from population-based listings in Baltimore, Md; Minneapolis, Minn; Portland, Ore; and the Monongahela Valley, Pa. Use of estrogen and progestin was determined by interview. Participants completed the Geriatric Depression Scale short form (GDS) and were considered depressed if they reported 6 or more of 15 possible symptoms of depression.
RESULTS: A total of 6.3% (72/1,150) of current estrogen users, 7.2% (142/1,964) of past estrogen users, and 9.0% (313/3,488) of never users reported 6 or more symptoms of depression ( P=.004). Current estrogen users had a decreased risk of reporting 6 or more depressive symptoms, compared with not current (past or never) users of estrogen (odds ratio [OR], 0.7; 95% CI, 0.5 to 0.9; P=.01), adjusted for living alone, bilateral oophorectomy, current smoking, physical activity, social network, self-perceived health, cognitive function, functional status, and antidepressant use. However, excluding women who use estrogen or progestin alone, we were unable to find an association between current use of combined estrogen plus progestin therapy and depressive symptoms (adjusted OR, 0.8; 95% CI, 0.5 to 1.4; P=.5).
CONCLUSIONS: This cross-sectional study found that current use of unopposed estrogen was associated with a decreased risk of depressive symptoms in older women. Additional studies are needed to understand the effect of combined estrogen and progestin therapy on the prevalence of depressive symptoms in older women.
estrogen replacement therapy
The members of the Study of Osteoporotic Fractures Research Group are listed in the Appendix.
Dr. Whooley is supported by a Research Career Development Award from the Department of Veterans Affairs Health Services Research and Development Service. This study was supported by a grant from the American Federation for Aging Research and by Public Health Service grants AG05394, AG05407, AR35582, AR35583, AR35584, and NS36016.
Depression Guideline Panel. Depression in Primary Care. Vol 1: Detection and Diagnosis. Clinical Practice Guideline. Washington, DC: U.S. Dept. of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research; 1993. AHCPR 93-0550.
Joffe H, Cohen LS. Estrogen, serotonin, and mood disturbance: where is the therapeutic bridge? Biol Psychiatry. 1998;44:798–811.
Jensvold MF, Halbreich U, Hamilton JA, eds. Psychopharmacology and Women: Sex, Gender and Hormones. Washington, DC: American Psychiatric Press; 1996.
Stahl SM. Basic psychopharmacology of antidepressants, part 2: estrogen as an adjunct to antidepressant treatment. J Clin Psychiatry. 1998;4:15–24.
Dennerstein L, Burrows GD, Hyman GJ, Sharpe K. Hormone therapy and affect. Maturitas. 1979;1:247–59.
Sherwin BB, Gelfand MM. Sex steroids and affect in the surgical menopause: a double-blind, cross-over study. Psychoneuroendocrinology. 1985;10:325–35.
Ditkoff EC, Crary WG, Cristo M, Lobo RA. Estrogen improves psychological function in asymptomatic postmenopausal women. Obstet Gynecol. 1991;78:991–5.
Derman RJ, Dawood MY, Stone S. Quality of life during sequential hormone replacement therapy—a placebo-controlled study. Int J Fertil Menopausal Stud. 1995;40:73–8.
George GC, Utian WH, Beaumont PJ, Beardwood CJ. Effect of exogenous oestrogens on minor psychiatric symptoms in postmenopausal women. S Afr Med J. 1973;47:2387–8.
Coppen A, Bishop M, Beard RJ. Effects of piperazine oestrone sulphate on plasma tryptophan, oestrogens, gonadotrophins and psychological functioning in women following hysterectomy. Curr Med Res Opin. 1977;4:29–36.
Campbell S, Whitehead M. Oestrogen therapy and the menopausal syndrome. Clin Obstet Gynaecol. 1977;4:31–47.
Strickler RC, Borth R, Cecutti A, et al. The role of oestrogen replacement in the climacteric syndrome. Psychol Med. 1977;7:631–9.
Thomson J, Oswald I. Effect of oestrogen on the sleep, mood, and anxiety of menopausal women. Br Med J. 1977;2:1317–9.
Coope J. Is oestrogen therapy effective in the treatment of menopausal depression? J R Coll Gen Pract. 1981;31:134–40.
Montgomery JC, Appleby L, Brincat M, et al. Effect of oestrogen and testosterone implants on psychological disorders in the climacteric. Lancet. 1987;1:297–9.
Saletu B, Brandstatter N, Metka M, et al. Double-blind, placebocontrolled, hormonal, syndromal and EEG mapping studies with transdermal oestradiol therapy in menopausal depression. Psychopharmacology. 1995;122:321–9.
Prange AJ. Estrogen may well affect response to antidepressant. JAMA. 1972;219:143–4.
Klaiber EL, Broverman DM, Vogel W, Kobayashi Y. Estrogen therapy for severe persistent depressions in women. Arch Gen Psychiatry. 1979;36:550–4.
Shapira B, Oppenheim G, Zohar J, Segal M, Malach D, Belmaker RH. Lack of efficacy of estrogen supplementation to imipramine in resistant female depressives. Biol Psychiatry. 1985;20:576–9.
Zohar J, Shapira B, Oppenheim G, Ayd FJ, Belmaker RH. Addition of estrogen to imipramine in female-resistant depressives. Psychopharmacol Bull. 1985;21:705–6.
Oppenheim G, Zohar J, Shapiro B, et al. The role of estrogen in treating resistant depression. In: Zohar J, Belmaker RH, eds. Treating Resistant Depression. Boston Mass: PMA Publishing; 1987:357–63.
Palinkas LA, Barrett-Connor E. Estrogen use and depressive symptoms in postmenopausal women. Obstet Gynecol. 1992;80:30–6.
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.
Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-anlysis. Obstet Gynecol. 1995;85:304–13.
Sherwin BB. Affective changes with estrogen and androgen replacement therapy in surgically menopausal women. J Affect Disord. 1988;14:177–87.
Cummings SR, Black DM, Nevitt MC, et al. Appendicular bone density and age predict hip fracture in women. The Study of Osteoporotic Fractures Research Group. JAMA. 1990;263:665–8.
Yesavage JA. Geriatric Depression Scale. Psychopharmacol Bull. 1988;24:709–11.
Sheikh JI, Yesavage JA. Geriatric Depression Scale (GDS): recent evidence and development of a shorter version. Clinical Gerontologist. 1986;5:165–73.
Gerety MB, Williams J Jr, Mulrow CD, et al. Performance of casefinding tools for depression in the nursing home: influence of clinical and functional characteristics and selection of optimal threshold scores. J Am Geriatr Soc. 1994;42:1103–9.
Paffenbarger RSJ, Wing AL, Hyde RT. Physical activity as an index of heart attack risk in college alumni. Am J Epidemiol. 1978;108:161–75.
Lubben JE. Assessing social networks among elderly populations. Fam Comm Health. 1988;11:42–52.
Lohman TG, Roche AF, Martorell R. Anthropometric Standardization Reference Manual. Champaign, Ill: Human Kinetics Books; 1988.
Wechsler D, Wechsler Adult Intelligence Scale-Revised. New York, NY: Psychological Corporation; 1988.
Pincus T, Summey JA, Soraci S Jr, Wallston KA, Hummon NP. Assessment of patient satisfaction in activities of daily living using a modified Standford Health Assessment Questionnaire. Arthritis Rheum. 1983;26:1346–53.
Sherwin BB. The impact of different doses of estrogen and progestin on mood and sexual behavior in postmenopausal women. J Clin Endocrinol Metab. 1991;72:336–43.
Arpels JC. The female brain hypoestrogenic continuum from the premenstrual syndrome to menopause. A hypothesis and review of supporting data. J Reprod Med. 1996;41:633–9.
Guicheney P, Leger D, Barrat J, et al. Platelet serotonin content and plasma tryptophan in peri- and postmenopausal women: variations with plasma oestrogen levels and depressive symptoms. Eur J Clin Invest. 1988;18:297–304.
Klaiber EL, Broverman DM, Vogel W, Kobayashi Y, Moriarty D. Effects of estrogen therapy on plasma MAO activity and EEG driving responses of depressed women. Am J Psychiatry. 1972;128:1492–8.
Price WA, Giannini AJ, Antidepressant effects of estrogen. J Clin Psychiatry. 1985;46:506.
Rubinow DR, Schmidt PJ, Roca CA. Estrogen-serotonin interactions: implications for affective regulation. Biol Psychiatry. 1998;44:839–50.
Fink G, Sumner BE, Rosie R, Grace O, Quinn JP. Estrogen control of central neurotransmission: effect on mood, mental state, and memory. Cell Mol Neurobiol. 1996;16:325–44.
Halbreich U, Rojansky N, Palter S, Tworek H, Hissin P, Wang K. Estrogen augments serotonergic activity in postmenopausal women. Biol Psychiatry. 1995;37:434–41.
Oppenheim G. Estrogen in the treatment of depression: neuropharmacological mechanisms. Biol Psychiatry. 1983;18:721–5.
Kumar MS, Chen CL, Muther TF. Changes in the pituitary and hypothalamic content of methionine-enkephalin during the estrous cycle of rats. Life Sci. 1979;25:1687–96.
Saletu B, Brandstatter N, Metka M, et al. Hormonal, syndromal and EEG mapping studies in menopausal syndrome patients with and without depression as compared with controls. Maturitas. 1996;23:91–105.
Coope J. Hormonal and non-hormonal interventions for menopausal symptoms. Maturitas. 1996;23:159–68.
McEwen BS, Biegon A, Davis PG, et al. Steroid hormones: humoral signals which alter brain cell properties and functions. Recent Prog Horm Res. 1982;38:41–92.
Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry. 1997;54:597–606.
Cauley JA, Cummings SR, Black DM, Mascioli SR, Seeley DG. Prevalence and determinants of estrogen replacement therapy in elderly women. Am J Obstet Gynecol. 1990;163:1438–44.
Barrett-Connor E. Postmenopausal estrogen and prevention bias. Ann Intern Med. 1991;115:455–6.
Sturgeon SR, Schairer C, Brinton LA, Pearson T, Hoover RN. Evidence of a healthy estrogen user survivor effect. Epidemiology. 1995;6:227–31.
Matthews KA, Kullr LH, Wing RR, Meilahn EN, Plantinga P. Prior to use of estrogen replacement therapy, are users healthier than nonusers? Am J Epidemiol. 1996;143:971–8.
Hulley S, Grady D, Bush 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;280:605–13.
Zweifel JE, O’Brien WH. A meta-analysis of the effect of hormone replacement therapy upon depressed mood. Psychoneuroendocrinology. 1997;22:189–212.
Lebowitz BD, Pearson JL, Schneider LS, et al. Diagnosis and treatment of depression in late life. Consensus statement update. JAMA. 1997;278:1186–90.
Johnson J, Weissman MM, Klerman GL. Service utilization and social morbidity associated with depressive symptoms in the community. JAMA. 1992;267:1478–83.
Wells KB, Stewart A, Hays RD, et al. The functioning and well-being of depressed patients. Results from the Medical Outcomes Study. JAMA. 1989;262:914–9.
Broadhead WE, Blazer DG, George LK, Tse CK. Depression, disability days, and days lost from work in a prospective epidemiologic survey. JAMA. 1990;264:2524–8.
Simon GE. Psychiatric disorder and functional somatic symptoms as predictors of health care use. Psychiatr Med. 1992;10:49–59.
Katon W, Berg AO, Robins AJ, Risse S. Depression—medical utilization and somatization. West J Med. 1986;144:564–8.
Spitzer RL, Kroenke K, Linzer M, et al. Health-related quality of life in primary care patients with mental disorders. Results from the PRIME-MD 1000 Study. JAMA. 1995;274:1511–7.
Whooley MA, Browner WS. Association between depressive symptoms and mortality in older women. Arch Int Med. 1998;158:2129–35.
Bryant HU, Dere WH. Selective estrogen receptor modulators: an alternative to hormone replacement therapy. Proc Soc Exp Biol Med. 1998;217:45–52.
Delmas PD, Bjarnason NH, Mitlak BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med. 1997;337:1641–7.
Hot T, Cox MB, Bryant HU, Draper MW. Selective estrogen receptor modulators and postmenopausal women’s health. J Women’s Health. 1997;6:523–31.
Mitlak BH, Cohen FJ. In search of optimal long-term female hormone replacement: the potential of selective estrogen receptor modulators. Horm Res. 1997;48:155–63.
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