Abstract
The effect of estrogen on the brain and body of women is a controversial topic that has received a tremendous amount of attention in the past few years. Recent reviews have focused on hormone replacement therapy (HRT), medical risks, and effects on brain metabolism, cognition, risk of Alzheimer’s disease, and mood. This article summarizes HRT and mood improvement in postmenopausal women. For nondepressed women, experimental designs provide no clear evidence for mood improvement associated with HRT, whereas observational studies are more likely to report mood improvement. There appears to be moderate evidence that HRT facilitates the improvement of clinical depression and the efficacy of antidepressants. Heterogeneity among studies makes it difficult to generalize and recommend HRT for mood improvement in postmenopausal women, but there is a clear need to examine the necessary duration of HRT for neuroprotection to decrease a woman’s risk for depression, cognitive dysfunction, and development of Alzheimer’s disease.
Similar content being viewed by others
References and Recommended Reading
Nelson HD, Humphrey LL, Nygren P, et al.: Postmenopausal hormone replacement therapy: scientific review. JAMA 2002, 288:872–881. Excellent summary regarding medical risk factors associated with HRT, including information from the Women’s Health Initiative study.
Meurer LN, Lena S: Cancer recurrence and mortality in women using hormone replacement therapy: meta-analysis. J Fam Pract 2002, 51:1056–62.
Zec RF, Trivedi MA: The effects of estrogen replacement therapy on neuropsychological functioning in postmenopausal women with and without dementia: a critical and theoretical review. Neuropsych Rev 2002, 12:65–109. Important summary regarding the literature on HRT and cognition.
Hogervorst E, Yaffe K, Richards M, et al.: Hormone replacement therapy for cognitive function in postmenopausal women (Cochrane Review). In The Cochrane Library, edn 2. Oxford: Updated Software; 2003.
Maki PM, Resnick SM: Effects of estrogen on patterns of brain activity at rest and during cognitive activity: a review of neuroimaging studies. Neuroimage 2001, 14:789–801. Information regarding HRT and brain metabolism.
Small GW: Estrogen effects on the brain. J Gend Specif Med 1998, 1:23–27.
Halbreich U: The role of estrogen in postmenopausal depression. Neurology 1997, 46(suppl):S16-S20.
Archer JSM: Relationship between estrogen, serotonin, and depression. Menopause 1999, 6:71–78.
Gallo R, Stomati M, Petraglia F, et al.: Central Nervous System. In Handbook of Experimental Pharmacology, Estrogens and Antiestrogens, Pharmacology and Clinical Application of Estrogens and Antiestrogens, vol 11. Edited by Oettel M, Schillinger E. New York: Springer; 1999:151–162.
Stoppe G, Dören M: Critical appraisal of effects of estrogen replacement therapy on symptoms of depressed mood. Arch Womens Ment Health 2002, 5:39–47. Helpful article regarding HRT and mood, including information on the “tonic” effect and “domino” theory.
Zweifel JE, O’Brien WH: A meta-analysis of the effect of hormone replacement therapy upon depressed mood. Psychoneuroendicronology 1997, 22:189–212. Excellent meta-analysis for HRT and mood.
Pearce J, Hawton K, Blake F: Psychological and sexual symptoms associated with the menopause and the effects of hormone replacement therapy. Br J Psychiatry 1995, 167:163–173.
Fedor-Freybergh P: The influence of estrogens on the wellbeing and mental performance in climacteric and postmenopausal women. Acta Obstet Gynecol Scand Supp 1977, 64:1–91.
Campbell S, Whitehead M: Estrogen therapy and the menopausal syndrome. Clin Obstet Gynaecol 1977, 4:31–47.
Schneider MA, Brotherton PL, Hales J: The effect of exogenous estrogens on depression in menopausal women. Med J Aust 1977, 2:162–163.
Ditkoff EC, Crary WG, Cristo M, Lobo RA: Estrogen improves psychological function in asymptomatic postmenopausal women. Obstet Gynecol 1991, 78:991–995.
Limouzin-Lamothe MA, Mairon N, Joyce CRB, Le Gal M: Quality of life after the menopause: influence of hormonal replacement therapy. Am J Obstet Gynecol 1994, 170:618–624.
Henderson VW: Estrogen, cognition, and a woman’s risk of Alzheimer’s disease. Am J Medicine 1997, 103:11S-18S.
Rudolph I, Zimmerman T, Kaminski K, et al.: Changes in psychic and somatic well-being and cognitive capabilities of per- and post-menopausal women after the use of a hormone replacement drug containing estradiol valerate and levonorgestrel. Methods Find Exp Clin Pharmacol 2000, 22:51–56.
Strickler RC, Borth R, Cecutti A, Cookson BA: The role of estrogen replacement in the climacteric syndrome. Psychol Med 1977, 7:631–639.
Polo-Kantola P, Portin R, Polo O, et al.: The effect of short-term estrogen replacement therapy on cognition: a randomized double-blind, crossover trial in postmenopausal women. Obstet Gynecol 1998, 91:459–466.
Wolf OT, Kudielka BM, Hellhammer DH, et al.: Two weeks of transdermal estradiol treatment in postmenopausal elderly women and its effect on memory and mood: verbal memory changes are associated with the treatment induced estradiol levels. Psychoneuroendocrinology 1999, 24:727–741.
Cagnacci A, Neri I, Tarabusi M, et al.: Effect of long-term local or systemic hormone replacement therapy on post-menopausal mood disturbances: influences of socio-economic and personality factors. Maturitas 1999, 31:111–116.
Duka T, Tasker R, McGowan JF: The effects of 3-week estrogen hormone replacement on cognition in elderly healthy females. Psychopharmacology 2000, 149:129–139.
Janowsky JS, Chevez B, Orwoll E: Sex steroids modify working memory. J Cogn Neurosci 2000, 12:407–414.
Cummings JA, Brizendine L: Comparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women. Menopause 2002, 9:253–263.
Schleifer LA, Justice AJ, de Wit H: Lack of effects of acute estradiol on mood in postmenopausal women. Pharmacol Biochem Behav 2002, 71:71–77.
Sherwin BB: Affective changes with estrogen and androgen replacement therapy in surgically menopausal women. J Affect Dis 1988, 14:177–187.
Kimura D: Estrogen replacement therapy may protect against intellectual decline. Horm Behav 1995, 29:312–321.
Sherwin BB: Estrogen and cognitive functioning in women. Proc Soc Exp Biol Med 1998, 217:17–22.
Whooley MA, Grady D, Cauley JA: Postmenopausal estrogen therapy and depressive symptoms in older women. Gen Intern Med 2000, 15:535–541.
Maki P, Zonderman A, Resnick S: Enhanced verbal memory in nondemented elderly women receiving hormone-replacement therapy. Am J Psychiatry 2001, 158:227–233.
Miller K, Connery JC, Rasgon NL, et al.: Mood symptoms and cognitive performance in women estrogen users and nonusers and men. J Am Ger Soc 2002, 50:1826–1830. Addresses the issue of including men in research regarding effects of HRT on mood and cognition.
Daly E, Gray A, Barlow D, et al.: Measuring the impact of menopausal symptoms on quality of life. Br J Med 1993, 307:836–840.
Barrett-Conner E, Kritz-Silverstein D: Estrogen replacement therapy and cognitive function in older women. JAMA 1993, 269:2637–2641.
Robinson D, Friedman L, Marcus R, et al.: Estrogen replacement therapy and memory in older women. J Am Ger Soc 1994, 42:919–922.
Jacobs DM, Tang MX, Stern Y, et al.: Cognitive function in nondemented older women who took estrogen after menopause. Neurology 1998, 50:368–373.
Stephens C, Ross N: The relationship between hormone replacement therapy use and psychological symptoms: no effects found in a New Zealand sample. Health Care Women Int 2002, 23:408–414.
Palinkas LA, Barrett-Conner E: Estrogen use and depressive symptoms in postmenopausal women. Obstet Gynecol 1992, 80:30–36.
Joffe H, Cohen LS: Estrogen, serotonin, and mood disturbance: where is the therapeutic bridge? Bio Psychiatry 1998, 44:798–811.
Pearlstein T, Rosen K, Stone AB: Mood disorders and menopause. Endocrinol Metab Clin North Am 1997, 26:279–294.
Schneider LS, Small GW, Clary CM: Estrogen replacement therapy (ERT) and antidepressant response to sertraline in older depressed women. Am J Geriatr Psychiatry 2001, 9:393–399.
Klaber EL, Broverman DM, Vogel W, Kobayashi Y: Estrogen therapy for severe persistent depression in women. Arc Gen Psychiatry 1979, 36:550–554.
Furuhjelm M, Karlgren E, Carlström K: The effect of estrogen therapy on somatic and psychical symptoms in postmenopausal women. Acta Obstet Gynecol Scand 1984, 63:655–661.
Montgomery JC, Brincat M, Tapp A, et al.: Effect of estrogen and testosterone implants on psychological disorders in the climacteric. Lancet 1987, 1:297–299.
Siddle NC, Fraser D, Whitehead M, et al.: Endometrial, physical and psychological effects of postmenopausal estrogen therapy with added dydrogesterone. Br J Obstet Gynecol 1990, 97:1101–1107.
Wiklund I, Berg G, Hammar M, et al.: Long-term effect of transdermal hormonal therapy on aspects of quality of life in postmenopausal women. Maturitas 1992, 14:225–236.
Derman RJ, Dawood M, Stone S: Quality of life during sequential hormone replacement therapy: a placebo controlled study. Int J Fertility 1995, 40:73–78.
Schneider LS, Arlow MR, Henderson VW, Pogoda JM: Effects of estrogen replacement therapy on response to tacrine in patients with Alzheimer’s disease. Neurology 1996, 46:1580–1584.
Carranza-Lira S, Valentino-Figueroa ML: Estrogen therapy for depression in postmenopausal women. Int J Gynecol Obstet 1999, 65:33–38.
Small GW: Hormone treatments for behavioral and psychological symptoms of dementia. Int Psychogeriatrics 2000, 12:291–295.
Rasgon NL, Small GW, Siddarth P, et al.: Estrogen use and brain metabolic change in older adults. Psychiatr Res 2001, 107:11–18.
Rasgon NL, Altshuler LL, Fairbanks LA, et al.: Estrogen replacement therapy in the treatment of major depressive disorder in perimenopausal women. J Clin Psychiatry 2002, 63:45–48.
Thompson J, Oswald I: Effect of estrogen on the sleep, mood and anxiety of menopausal women. BMJ 1977, 2:1317–1319.
Coope J: Is estrogen therapy effective in the treatment of menopausal depression? J R Coll Gen Pract 1981, 31:134–140.
Pearce J, Hawton K, Blake F, et al.: Psychological effects of continuation versus discontinuation of hormone replacement therapy by estrogen implants: a placebo-controlled study. J Psychosomatic Res 1997, 42:177–186.
Hays J, Ockene JK, Brunner RL, et al.: Effects of estrogen plus progestin on health-related quality of life. N Engl J Med 2003, 348:1839–1854.
Carlson LE, Sherwin BB: Steroid hormones, memory and mood in a healthy elderly population. Psychoneuroendocrinology 1998, 23:583–603.
Barrett-Connor E, Kritz-Silverstein D: Gender differences in cognitive function with age: The Rancho Bernardo Study. J Am Geriatr Soc 1999, 47:159–164.
Mulnard RA, Cotman CW, Kawas C, et al.: Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. JAMA 2000, 283:1007–1015.
Soares CN, Cohen LS: The perimnopause, depressive disorders, and hormonal variability. Sao Paulo Med J 2001, 119:78–83.
Utian WH: The true clinical features of menopause and oophorectomy and their response to estrogen therapy. S Afr Med J 1972, 46:732–737.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Miller, K.J. The other side of estrogen replacement therapy: Outcome study results of mood improvement in estrogen users and nonusers. Curr Psychiatry Rep 5, 439–444 (2003). https://doi.org/10.1007/s11920-003-0082-5
Issue Date:
DOI: https://doi.org/10.1007/s11920-003-0082-5