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Treatment of Menopause-Related Mood Disturbances

Published online by Cambridge University Press:  07 November 2014

Abstract

More than 1.7 million American women are expected to reach menopause each year. Recent Canadian statistics show that a 50-year-old woman can now expect to live until her mid-80s, which implies living at least one-third of her life after menopause. The menopausal transition is typically marked by intense hormonal fluctuations, accompanied by vasomotor symptoms (eg, hot flashes, night sweats), sleeps disturbance, and changes in sexual function, as well as increased risk for osteoporosis, cardiovascular disease, and cognitive decline. More importantly, recent studies have demonstrated a significant association between menopausal transition and a higher risk for developing depression. In the post-Women's Health Initiative Study era, physicians and patients are questioning the safety and efficacy of long-term hormone therapy use. This article reviews the current literature on the benefits and risks of using hormone therapy for the treatment of menopause-related mood disturbances and alternate strategies currently available for the management of menopause-related problems, including antidepressants, complementary and alternative medicine, and selective estrogen receptor modulators.

Type
Review Articles
Copyright
Copyright © Cambridge University Press 2005

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References

REFERENCES

1. Female population by age, race, and Hispanic or Latino origin for the United States: Census 2000 PHC-T9. Washington, DC: United States Bureau of the Census; 2000.Google Scholar
2. Statistics Canada. CANSIM II. Ottawa, Canada: Statistics Canada; 2000.Google Scholar
3. Fried, L. Relating Aging and outcomes of menopause. Paper presented at: Biology of the Perimenopause: Impact on Health and Aging. 05 26-27, 2004; Bethesda, Maryland.Google Scholar
4. Wise, PM, Krajnak, KM, Kashon, ML. Menopause: the aging of multiple pacemakers. Science. 1996;273:6770.Google Scholar
5. Shifren, JL, Schiff, I. The aging ovary. J Womens Health Gend Based Med. 2000;9(suppl 1):S3S7.CrossRefGoogle ScholarPubMed
6. Clinical challenges of perimenopause: Consensus opinion of The North American Menopause Society. Menopause. 2000;7:513.Google Scholar
7. Adashi, EY. The climacteric ovary as a functional gonadotropin-driven androgen-producing gland. Fertil Steril. 1994;62:2027.CrossRefGoogle ScholarPubMed
8. Schmidt, PJ, Roca, CA, Bloch, M, Rubinow, DR. The perimenopause and affective disorders. Seminars Repro Endo. 1997;15:91100.Google Scholar
9. Stone, AB, Pearlstein, TB. Evaluation and treatment of changes in mood, sleep, and sexual functioning associated with menopause. Obstet Gynecol Clin North Am. 1994;21:391403.Google Scholar
10. Anderson, E, Hamburger, S, Liu, JH, Rebar, RW. Characteristics of menopausal women seeking assistance. Am J Obstet Gynecol. 1987;156:428433.CrossRefGoogle ScholarPubMed
11. Hay, AG, Bancroft, J, Johnstone, EC. Affective symptoms in women attending a menopause clinic. Br J Psychiatry. 1994;164:513516.Google Scholar
12. Burt, VK, Altshuler, LL, Rasgon, N. Depressive symptoms in the perimenopause: prevalence, assessment, and guidelines for treatment. Harv Rev Psychiatry. 1998;6:121132.Google Scholar
13. 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;4:214220.Google Scholar
14. Kaufert, PA, Gilbert, P, Tate, R. The Manitoba Project: a re-examination of the link between menopause and depression. Maturitas. 1992;14:143155.Google Scholar
15. Freeman, EW, Sammel, MD, Liu, L, et al. Hormones and menopausal status as predictors of depression in women in transition to menopause. Arch Gen Psychiatry. 2004;61:6270.Google Scholar
16. Schmidt, PJ, Haq, N, Rubinow, DR. A longitudinal evaluation of the relationship between reproductive status and mood in perimenopausal women. Am J Psychiatry. 2004;161:22382244.CrossRefGoogle ScholarPubMed
17. Bromberger, JT, Harlow, S, Avis, N, Kravitz, HM, Cordal, A. Racial/ethnic differences in the prevalence of depressive symptoms among middle-aged women: the Study of Women's Health Across the Nation (SWAN). Am J Public Health. 2004;94:13781385.CrossRefGoogle Scholar
18. Campbell, S, Whitehead, M. Oestrogen therapy and the menopausal syndrome. Clin Obstet Gynaecol. 1977;4:3147.Google Scholar
19. Burger, HG, Dudley, EC, Hopper, JL, et al. The endocrinology of the menopausal transition: a cross-sectional study of a population-based sample. J Clin Endocrinol Metab. 1995;80:35373545.Google ScholarPubMed
20. Joffe, H, Cohen, LS. Estrogen, serotonin, and mood disturbance: where is the therapeutic bridge? Biol Psychiatry. 1998;44:798811.Google Scholar
21. Maggi, A, Perez, J. Role of female gonadal hormones in the CNS: clinical and experimental aspects. Life Sci. 1985;37:893906.Google Scholar
22. Genazzani, AR, Lucchesi, A, Stomati, M, et al. Effects of sex steroid hormones on the neuroendocrine system. Eur J Contracept Reprod Health Care. 1997;2:6369.Google Scholar
23. Kuiper, GG, Enmark, E, Pelto-Huikko, M, Nilsson, S, Gusstafsson, JA. Cloning of a model receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A. 1996;93:59255930.Google Scholar
24. Mendelsohn, ME, Karas, RH. The protective effects of estrogen on the cardiovascular system. N Eng J Med. 1999;340(23):18011811.CrossRefGoogle ScholarPubMed
25. McEwen, BS, Alves, SE. Estrogen actions in the central nervous system. Endocrinol Rev. 1999;20:279307.Google Scholar
26. Stahl, SM. Sex and psychopharmacology: is natural estrogen a psychotropic drug in women? Arch Gen Psychiatry. 2001;58:537538.CrossRefGoogle ScholarPubMed
27. Halbreich, U, Kahn, LS. Role of estrogen in the aetiology and treatment of mood disorders. CNS Drugs. 2001;15:797817.CrossRefGoogle ScholarPubMed
28. Garlow, S, Musselman, D, Nemeroff, C. The neurochemistry of mood disorders: clinical studies. In: Charney, D, Nestler, E, Bunney, B, eds. Neurobiology of Mental Illness. New York, NY: Oxford University Press; 1999:348364.Google Scholar
29. Bethea, CL, Lu, NZ, Gundlah, C, Streicher, JM. Diverse actions of ovarian steroids in the serotonin neural system. Front Neuroendocrinol. 2002;23:41100.Google Scholar
30. Kugaya, A, Epperson, CN, Zoghbi, S, et al. Increase in prefrontal cortex serotonin 2A receptors following estrogen treatment in postmenopausal women. Am J Psychiatry. 2003;160:15221524.Google Scholar
31. Holte, A. Menopause, mood and hormone replacement therapy: methodological issues. Maturitas. 1998;29:518.Google Scholar
32. Ramachandran, C, Fleisher, D. Transdermal delivery of drugs for the treatment of bone diseases. Adv Drug Deliv Rev. 2000;42:197223.CrossRefGoogle ScholarPubMed
33. Scott, RT Jr, Ross, B, Anderson, C, Archer, DE Pharmacokinetics of percutaneous estradiol: a crossover study using a gel and a transdermal system in comparison with oral micronized estradiol. Obstet Gynecol. 1991;77:758764.Google Scholar
34. Smith, RN, Studd, JW, Zamblera, D, Holland, EF. A randomised comparison over 8 months of 100 micrograms and 200 micrograms twice weekly doses of transdermal oestradiol in the treatment of severe premenstrual syndrome. Br J Obstet Gynaecol. 1995;102:475484.Google Scholar
35. Gregoire, AJ, Kumar, R, Everitt, B, Henderson, AF, Studd, JW. Transdermal oestrogen for treatment of severe postnatal depression. Lancet. 1996;347:930933.Google Scholar
36. Schmidt, PJ, Nieman, L, Danaceau, MA, et al. Estrogen replacement in perimenopauserelated depression: a preliminary report. Am J Obstet Gynecol. 2000;183:414420.CrossRefGoogle ScholarPubMed
37. Soares, CN, Almeida, OP, Joffe, H, Cohen, LS. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebocontrolled trial. Arch Gen Psychiatry. 2001;58:529534.Google Scholar
38. Fraser, I, Wang, Y. New delivery systems for hormone replacement therapy. In: Studd, J, ed. The Management of Menopause-Annual Review. London, United Kingdom: Parthenon; 1998:101110.Google Scholar
39. Coope, J, Thomson, JM, Poller, L. Effects of “natural oestrogen” replacement therapy on menopausal symptoms and blood clotting. Br Med J. 1975;4:139143.Google Scholar
40. Strickler, RC, Borth, R, Cecutti, A, et al. The role of oestrogen replacement in the climacteric syndrome. Psychol Med. 1977;7:631639.Google Scholar
41. Thompson, J, Oswald, I. Effect of oestrogen on the sleep, mood, and anxiety of menopausal women. Br Med J. 1977;2:13171319.Google Scholar
42. George, GC, Utian, WH, Beaumont, PJ, Beardwood, CJ. Effect of exogenous oestrogens on minor psychiatric symptoms in postmenopausal women. S Afr Med J. 1973;47:23872388.Google Scholar
43. Coppen, A, Bishop, M, Beard, R. Effects of piperazine oestrone sulphate on plasma tryptophan, oestrogens, gonadotrophins and psychological functioning in women following hysterectomy. Curr Med Res Opin. 1977;4:2936.CrossRefGoogle Scholar
44. Saletu, B, Brandstatter, N, Metka, M, et al. Double-blind, placebo-controlled, hormonal, syndromal and EEG mapping studies with transdermal oestradiol therapy in menopausal depression. Psychopharmacology (Berl). 1995;122:321329.CrossRefGoogle ScholarPubMed
45. Morrison, MF, Kallan, MJ, Ten Have, T, et al. Lack of efficacy of estradiol for depression in postmenopausal women: a randomized, controlled trial. Biol Psychiatry. 2004;55:406412.Google Scholar
46. Cohen, LS, Soares, CN, Poitras, JR, Prouty, J, Alexander, AB, Shifren, JL. Short-term use of estradiol for depression in perimenopausal and postmenopausal women: a preliminary report. Am J Psychiatry. 2003;160:15191522.Google Scholar
47. Bagger, YZ, Tanko, LB, Alexandersen, P, et al. Early postmenopausal hormone therapy may prevent cognitive impairment later in life. Menopause. 2005;12:1217.Google Scholar
48. Cassano, P, Soares, CN, Cohen, LS, Lyster, AK, Fava, M. Sex and age-related differences in major depressive disorder with comorbid anxiety treate with fluoxetine. Arch Women Ment Health. 2004;7(3):167171.Google Scholar
49. Cassano, P, Soares, CN, Cusin, C, et al. Antidepressant response and well-being in pre-, peri-, and postmenopausal women with major depressive disorder treated with fluoxetine. Psychother Psychosom. In press.Google Scholar
50. Komstein, SG, Schatzberg, AF, Thase, ME, et al. Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry. 2000;157:14451452.Google Scholar
51. Schneider, LS, Small, GW, Hamilton, SH, et al. Estrogen replacement and response to fluoxetine in a multicenter geriatric depression trial. Fluoxetine Collaborative Study Group. Am J Geriatr Psychiatry. 1997;5:97106.Google Scholar
52. Amsterdam, J, Garcia-Espana, F, Fawcett, J, et al. Fluoxetine efficacy in menopausal women with and without estrogen replacement. J Affect Disord. 1999;55:1117.CrossRefGoogle ScholarPubMed
53. Schneider, LS, Small, GW, Clary, CM. Estrogen replacement therapy and antidepressant response to sertraline in older depressed women. Am J Geriatr Psychiatry. 2001;9:393399.Google Scholar
54. Soares, CN, Poitras, JR, Prouty, J, et al. Efficacy of citalopram as a monotherapy or as an adjunctive treatment to estrogen therapy for perimenopausal and postmenopausal women with depression and vasomotor symptoms. J Clin Psychiatry. 2003;64:473479.Google Scholar
55. Bethea, CL, Pecins-Thompson, M, Schutzer, WE, Gundlah, C, Lu, ZN. Ovarian steroids and serotonin neural function. Mol Neurobiol. 1998;18:87123.Google Scholar
56. de Wit, H, Schmitt, L, Purdy, R, Hauger, R. Effects of acute progesterone administration in healthy postmenopausal women and normally-cycling women. Psychoneuroendocrinology. 2001;26:697710.Google Scholar
57. Rupprecht, R, Holsboer, F. Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci. 1999;22:410416.CrossRefGoogle ScholarPubMed
58. Westhoff, C, Wieland, D, Tiezzi, L. Depression in users of depo-medroxyprogesterone acetate. Contraception. 1995;51:351354.CrossRefGoogle ScholarPubMed
59. Wieland, S, Belluzzi, J, Hawkinson, JE, et al. Anxiolytic and anticonvulsant activity of a synthetic neuroactive steroid Co 3-0593. Psychopharmacology (Berl). 1997;134:4654.CrossRefGoogle ScholarPubMed
60. Gupta, N, O'Brien, R, Jacobsen, LJ, et al. Mood changes in adolescents using depotmedroxyprogesterone acetate for contraception: a prospective study. J Pediatr Adolesc Gynecol. 2001;14:7176.CrossRefGoogle ScholarPubMed
61. Civic, D, Scholes, D, Ichikawa, L, et al. Depressive symptoms in users and non-users of depot medroxyprogesterone acetate. Contraception. 2000;61:385390.CrossRefGoogle ScholarPubMed
62. Morrison, MF. Androgens in the elderly: will androgen replacement therapy improve mood, cognition, and quality of life in aging men and women. Psychopharmacol Bull. 1997;33:293296.Google ScholarPubMed
63. Zumoff, B, Bradlow, H. Sex difference in the metabolism of dehydroisoandrosterone sulfate. J Clin Endocrinol Metab. 1980;51:334336.Google Scholar
64. Davis, S. The therapeutic use of androgens in women. J Steroid Biochem Mol Biol. 1999;69:177184.CrossRefGoogle ScholarPubMed
65. Morley, JE. Androgens and aging. Maturitas. 2001;38613871.Google Scholar
66. Archer, J. The influence of testosterone on human aggression. Br J Psychol. 1991;82(pt 1):128.Google Scholar
67. Christiansen, K. Behavioural effects of androgen in men and women. J Endocrinol. 2001;170:3948.Google Scholar
68. Cashdan, E. Hormones, sex, and status in women. Horm Behav. 1995;29:354366.CrossRefGoogle ScholarPubMed
69. Sherwin, BB, Gelfand, MM. Sex steroids and affect in the surgical menopause: a double-blind, cross-over study. Psychoneuroendocrinology. 1985;10:325335.Google Scholar
70. Shifren, JL, Braunstein, GD, Simon, JA, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med. 2000;343(10):682688.Google Scholar
71. Barrett-Connor, E, von Muhlen, D, Laughlin, GA, Kripke, A. Endogenous levels of dehydroepiandrosterone sulfate, but not other sex hormones, are associated with depressed mood in older women: the Rancho Bernardo Study. J Am Geriatr Soc. 1999;47:685691.CrossRefGoogle Scholar
72. Yaffe, K, Ettinger, B, Pressman, A, et al. Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study. Biol Psychiatry. 1998;43:694700.Google Scholar
73. Rossouw, JE, Anderson, GL, Prentice, RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321333.Google Scholar
74. Anderson, GL, Limacher, M, Assaf, AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004;291:17011712.Google ScholarPubMed
75. Hays, J, Ockene, JK, Brunner, RL, et al. Effects of estrogen plus progestin on health-related quality of life. N Engl J Med. 2003;348:18391854.Google Scholar
76. McIntosh, J, Blalock, SJ. Effects of media coverage of Women's Health Initiative study on attitudes and behavior of women receiving hormone replacement therapy. Am J Health Syst Pharm. 2005;62:6974.Google Scholar
77. Soares, CN. Hormones and mental health: where do we stand in the post-WHI era? Rev Bras Psiquiatr. 2003;25:198199.CrossRefGoogle ScholarPubMed
78. Notelovitz, M. The clinical practice impact of the Women's Health Initiative: political vs biologic correctness. Maturitas. 2003;44:39.Google Scholar
79. Haskell, SG. After the Women's Health Initiative: postmenopausal women's experience with discontinuing estrogen replacement therapy. J Womens Health. 2004;13:438442.Google Scholar
80. Bair, YA, Gold, EB, Azari, RA, et al. Use of conventional and complementary health care during the transition to menopause: longitudinal results from the Study of Women's Health Across the Nation (SWAN). Menopause. 2005;12:3139.Google Scholar
81. Suvanto-Luukkonen, E, Koivunen, R, Sundstrom, H, et al. Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, double-blind study. Menopause. 2005;12:1826.Google Scholar
82. Stearns, V, Beebe, KL, Iyengar, M, Dube, E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA. 2003;289:28272834.CrossRefGoogle ScholarPubMed
83. Mayeux, R. Can estrogen or selective estrogen-receptor modulators preserve cognitive function in elderly women? N Engl J Med. 2001;344:12421244.CrossRefGoogle ScholarPubMed
84. Genazzani, AR, Bernardi, F, Stomati, M, et al. Raloxifene analog LY 117018 effects on central and peripheral beta-endorphin. Gynecol Endocrinol. 1999;13:249258.Google Scholar
85. Sumner, BE, Grant, KE, Rosie, R, Hegele-Hartung, C, Fritzemeier, KH, Fink, G. Effects of tamoxifen on serotonin transporter and 5-hydroxytryptamine(2A) receptor binding sites and mRNA levels in the brain of ovariectomized rats with or without acute estradiol replacement. Brain Res Mol Brain Res. 1999;73:119128.Google Scholar
86. Wissink, S, van der Burg, B, Katzenellenbogen, BS, van der Saag, PT. Synergistic activation of the serotonin-1A receptor by nuclear factor-kappa B and estrogen. Mol Endocrinol. 2001;15:543552.Google Scholar
87. Thompson, DS, Spanier, CA, Vogel, VG. The relationship between tamoxifen, estrogen, and depressive symptoms. Breast J. 1999;5:375382.CrossRefGoogle ScholarPubMed
88. Fisher, B, Costantino, JP, Wickerham, DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90:13711388.Google Scholar
89. Cathcart, CK, Jones, SE, Pumroy, CS, Peters, GN, Knox, SM, Cheek, JH. Clinical recognition and management of depression in node negative breast cancer patients treated with tamoxifen. Breast Cancer Res Treat. 1993;27:277281.Google Scholar
90. Yaffe, K, Krueger, K, Sarkar, S, et al. Cognitive function in postmenopausal women treated with raloxifene. N Engl J Med. 2001;344:12071213.Google Scholar
91. Nickelsen, T, Lufkin, EG, Riggs, BL, Cox, DA, Crook, TH. Raloxifene hydrochloride, a selective estrogen receptor modulator: safety assessment of effects on cognitive function and mood in postmenopausal women. Psychoneuroendocrinology. 1999;24:115128.Google Scholar
92. Strickler, R, Stovall, DW, Merritt, D, Shen, W, Wong, M, Silfen, SL. Raloxifene and estrogen effects on quality of life in healthy postmenopausal women: a placebo-controlled randomized trial. Obstet Gynecol. 2000;96:359365.Google ScholarPubMed
93. Jarkova, NB, Martenyi, F, Masanauskaite, D, Walls, EL, Smetnik, VP, Pavo, I. Mood effect of raloxifene in postmenopausal women. Maturitas. 2002;42:7175.CrossRefGoogle ScholarPubMed
94. Grigoriadis, S, Kenndy, SH, Srinivisan, J, McIntyre, RS, Fulton, K. Antidepressant augmentation with raloxifene. J Clin Psychopharmacol. 2005;25:9698.Google Scholar
95. Kessel, B, Kronenberg, F. The role of complementary and alternative medicine in management of menopausal symptoms. Endocrinol Metab Clin North Am. 2004;33:717739.Google Scholar
96. Huntley, AL, Ernst, E. Soy for the treatment of perimenopausal symptoms--a systematic review. Maturitas. 2004;47:19.Google Scholar
97. Pockaj, BA, Loprinzi, CL, Sloan, JA, et al. Pilot evaluation of black cohosh for the treatment of hot flashes in women. Cancer Invest. 2004;22:515521.Google Scholar
98. Taylor, M. Alternatives to HRT: an evidence-based review. Int J Fertil Womens Med. 2003;48:6468.Google Scholar
99. Soares, CN, Arsenio, HC, Bankier, B, et al. Impact of escitalopram versus norethindrone acetate and ethinyl estradiol on depression, vasomotor symptoms, and quality of life in peri and postmenopausal women: a randomized trial. Paper presented at: annual meeting of the American College of NeuroPsychiatry. December 7-11, 2003; San Juan, PR.Google Scholar
100. Evans, ML, Pritts, E, Vittinghoff, E, McClish, K, Morgan, KS, Jaffe, RB. Management of postmenopausal hot flushes with venlafaxine hydrochloride: a randomized, controlled trial. Obstet Gynecol. 2005;105:161166.Google Scholar