Mass General Hospital

Harvard Medical School

Menopausal Symptoms

Webcasts

“Depression During the Menopausal Transition: A Critical Review of Risk Factors and Evidence-Based Treatment Strategies.”
From the Congress on Women’s Mental Health meeting in Melbourne, Australia, March 2008.
Lee S. Cohen, MD; Hadine Joffe, MD, MSc; Claudio N. Soares, MD, PhD, FRCPC; Joyce T. Bromberger, PhD, MSW; and Martha Hickey, FRANZCOG, MD

Menopause Transition

Dennerstein L, Dudley EC, Hopper JL, Guthrie JR, Burger HG. A prospective population-based study of menopausal symptoms. Obstet Gynecol 2000;96:351-8.

Guthrie JR, Dennerstein L, Taffe JR, Donnelly V. Health care-seeking for menopausal problems. Climacteric 2003;6:112-7.

Joffe H, Cohen LS. Estrogen, serotonin and mood disturbance: Where is the therapeutic bridge? Biological Psychiatry 1998; 44: 798-811.

Proceedings from the NIH State-of-the-Science Conference on Management of Menopause-Related Symptoms, March 21-23, 2005, Bethesda, Maryland, USA. Am J Med 2005;118 Suppl 12B:1-171.

Santoro N, Sherman SS, Joffe H, Newton K, Grady D, Freeman E, Schmidt P, Stearns V; Endicott J, Ganz P, Low Dog T, Monroe S, Shames D, Weber A, Zeitlian G. New intervention strategies for menopausal symptoms. Executive Summary of NIH meeting November 2006.

Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, Woods N. Executive summary: Stages of Reproductive Aging Workshop (STRAW). Fertil Steril 2001;76:874-8.

Hot Flashes

Symptoms

Freedman RR, Benton MD, Genik RJ, 2nd, Graydon FX. Cortical activation during menopausal hot flashes. Fertil Steril 2006;85:674-8.

Freeman EW, Sammel MD, Lin H, Gracia CR, Pien GW, Nelson DB, Sheng L. Symptoms associated with menopausal transition and reproductive hormones in midlife women. Obstet Gynecol 2007;110:230-40

Freeman EW, Sammel MD, Lin H, Gracia CR, Kapoor S, Ferdousi T. The role of anxiety and hormonal changes in menopausal hot flashes. Menopause 2005;12:258-66.

Gold EB, Colvin A, Avis N, Bromberger J, Greendale GA, Powell L, Sternfeld B, Matthews K. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: Study of women’s health across the nation. Am J Public Health 2006;96:1226-35.

Joffe H, Hall JE, Soares CN, Hennen J, Reilly CJ, Carlson K, Cohen LS. Vasomotor symptoms are associated with depression in perimenopausal women seeking primary care. Menopause 2002 Nov-Dec;9(6):392-8.

Kravitz HM, Ganz PA, Bromberger J, Powell LH, Sutton-Tyrrell K, Meyer PM. Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition. Menopause 2003;10:19-28

Kronenberg F. Hot flashes: epidemiology and physiology. Ann N Y Acad Sci 1990;592:52-86.

Stearns V, Ullmer L, Lopez JF, Smith Y, Isaacs C, Hayes D. Hot flushes. Lancet 2002;360:1851-61.

Young T, Rabago D, Zgierska A, Austin D, Laurel F. Objective and subjective sleep quality in premenopausal, perimenopausal, and postmenopausal women in the Wisconsin Sleep Cohort Study. Sleep 2003;26:667-72.

Treatment

Joffe H, Soares CN, Cohen LS. Assessment and treatment of hot flushes and menopausal mood disturbance. Psychiatr Clin North Am. 2003 Sep;26(3):563-80.

Nelson HD, Vesco KK, Haney E, Fu R, Nedrow A, Miller J, Nicolaidis C, Walker M, Humphrey L. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006;295:2057-71.

Bachmann GA, Schaefers M, Uddin A, Utian W. Lowest effective transdermal 17?-estradiol dose for relief of hot flushes in postmenopausal women: A randomized controlled trial. Obstet Gynecol 2007;110:771-9.

Ettinger B. Vasomotor symptom relief versus unwanted effects: role of estrogen dosage. Am J Med 2005;118 Suppl 12B:74-8.

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;105:161-6.

Faure ED, Chantre P, Mares P. Effects of a standardized soy extract on hot flushes: a multicenter, double-blind, randomized, placebo-controlled study. Menopause 2002 Sep-Oct;9(5):329-34.

Gordon PR, Kerwin JP, Boesen KG, Senf J. Sertraline to treat hot flashes: a randomized controlled, double-blind, crossover trial in a general population. Menopause 2006;13:568-75.

Grady D, Cohen B, Tice J, Kristof M, Olyaie A, Sawaya GF. Ineffectiveness of sertraline for treatment of menopausal hot flushes: a randomized controlled trial. Obstet Gynecol 2007;109:823-30.

Guttuso T Jr, Kurlan R, McDermott MP, Kieburtz K. Gabapentin’s effects on hot flashes in postmenopausal women: a randomized controlled trial. Obstet Gynecol 2003 Feb;101(2):337-45.

Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials. Ann Intern Med 2002 Nov 19;137(10):805-13.

Loprinzi CL, Sloan JA, et al. Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol 2002 Mar 15;20(6):1578-83.

Loprinzi CL, Kugler JW, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet 2000 Dec 16;356(9247):2059-63.

Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med 2006;145:869-79.

Pandya KJ, Morrow GR, Roscoe JA, et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial. Lancet 2005;366:818-824.

Rapkin AJ. Vasomotor symptoms in menopause: Physiologic condition and central nervous system approaches to treatment. Am J Obstet Gynecol 2006.

Soares CN, Joffe H, Viguera AC, Petrillo LF, Rydzewski M, Yehezkel BS, Somley B, Cohen LS. Paroxetine versus placebo for midlife women after hormone therapy discontinuation. Am J Med In Press.

Soares CN, Arsenio H, Joffe H, Bankier B, Cassano P, Petrillo LF, Cohen LS. Escitalopram versus ethinyl estradiol and norethindrone acetate for symptomatic peri- and postmenopausal women: impact on depression, vasomotor symptoms, sleep, and quality of life. Menopause 2006;13:780-6.

Soares CN, Poitras JR, Shifren JL, Alexander AB. 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(4): 673-679.

Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA 2003;289:2827-34.

Steingold KA, Laufer L, Chetkowski RJ, DeFazio JD, Matt DW, Meldrum DR, Judd HL. Treatment of hot flashes with transdermal estradiol administration. J Clin Endocrinol Metab 1985;61:627-32.

Suvanto-Luukkonen E, Koivunen R, Sundstrom H, Bloigu R, Karjalainen E, Haiva-Mallinen L, Tapanainen JS. Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, double-blind study. Menopause 2005;12:18-26.

Mood (Depression and Anxiety)

Symptoms

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;4:213-20.

Bromberger JT, Matthews KA, Schott LL, Brockwell S, Avis NE, Kravitz HM, Everson-Rose SA, Gold EB, Sowers M, Randolph JF, Jr. Depressive symptoms during the menopausal transition: The Study of Women’s Health Across the Nation (SWAN). J Affect Disord 2007.

Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL. Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles. Arch Gen Psychiatry. 2006 Apr;63(4):385-90.

Freeman EW, Sammel D, Lin H, Nelson DB. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006 Apr;63(4):375-82.

Freeman EW, Sammel MD, Lin H, Gracia CR, Kapoor S, Ferdousi T. The role of anxiety and hormonal changes in menopausal hot flashes. Menopause 2005;12:258-66.

Freeman EW, Sammel MD, Liu L, Gracia CR, Nelson DB, Hollander L. Hormones and menopausal status as predictors of depression in women in transition to menopause. Arch Gen Psychiatry 2004;61:62-70.

Joffe H, Hall JE, Soares CN, Hennen J, Reilly CJ, Carlson K, Cohen LS. Vasomotor symptoms are associated with depression in perimenopausal women seeking primary care. Menopause 2002 Nov-Dec;9(6):392-8.

Treatment

Joffe H, Soares CN, Cohen LS. Assessment and treatment of hot flushes and menopausal mood disturbance. Psychiatr Clin North Am. 2003 Sep;26(3):563-80.

Joffe H, Soares CN, Petrillo LF, Viguera AC, Somley BL, Koch JK, Cohen LS. Treatment of depression and menopause-related symptoms with the serotonin-norepinephrine reuptake inhibitor duloxetine. J Clin Psychiatry 2007;68:943-50.

Joffe H, Groninger H, Soares C, Nonacs R, Cohen LS. An open trial of mirtazapine in menopausal women with depression unresponsive to estrogen replacement therapy. J Womens Health Gend Based Med 2001 Dec;10(10):999-1004.

Schmidt PJ, Nieman L, Danaceau MA, Tobin MB, Roca CA, Murphy JH, Rubinow DR. Estrogen replacement in perimenopause-related depression: a preliminary report. Am J Obstet Gynecol 2000; 183: 414-20.

Soares CN, Arsenio H, Joffe H, Bankier B, Cassano P, Petrillo LF, Cohen LS. Escitalopram versus ethinyl estradiol and norethindrone acetate for symptomatic peri- and postmenopausal women: impact on depression, vasomotor symptoms, sleep, and quality of life. Menopause 2006;13:780-6.

Soares CN, Poitras JR, Shifren JL, Alexander AB. 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(4): 673-679.

Soares CN, Almeida OP, Joffe H, Cohen LS. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 2001; 58: 529-34.

Sleep

Symptoms

Erlik Y, Tataryn IV, Meldrum DR, Lomax P, Bajorek JG, Judd HL. Association of waking episodes with menopausal hot flushes. JAMA 1981;245:1741-4.

Freedman RR, Roehrs TA. Sleep disturbance in menopause. Menopause 2007.

Freedman RR, Roehrs TA. Lack of sleep disturbance from menopausal hot flashes. Fertil Steril 2004;82:138-44.

Ohayon MM. Severe hot flashes are associated with chronic insomnia. Arch Intern Med 2006;166:1262-8.

Savard J, Davidson JR, Ivers H, Quesnel C, Rioux D, Dupere V, Lasnier M, Simard S, Morin CM. The association between nocturnal hot flashes and sleep in breast cancer survivors. J Pain Symptom Manage 2004;27:513-22.

Shaver J, Giblin E, Lentz M, Lee K. Sleep patterns and stability in perimenopausal women. Sleep 1988;11:556-61.

Thurston RC, Blumenthal JA, Babyak MA, Sherwood A. Association between hot flashes, sleep complaints, and psychological functioning among healthy menopausal women. Int J Behav Med 2006;13:163-72.

Woodward S, Freedman RR. The thermoregulatory effects of menopausal hot flashes on sleep. Sleep 1994;17:497-501.

Treatment

Dorsey CM, Lee KA, Scharf MB. Effect of zolpidem on sleep in women with perimenopausal and postmenopausal insomnia: a 4-week, randomized, multicenter, double-blind, placebo-controlled study. Clin Ther 2004;26:1578-86.

Joffe H, Petrillo LF, Viguera AC, Koukopoulos A, Silver-Heilman K, Farrell A, Yu G, Pollack MH, Cohen LS. Eszopiclone improves insomnia, depressive and anxious symptoms in perimenopausal and postmenopausal women with hot flashes. At: American College of Neuropsychopharmacology. Boca Raton, FL; December 11, 2007.

Soares CN, Joffe H, Rubens R, Caron J, Roth T, Cohen L. Eszopiclone in patients with insomnia during perimenopause and early postmenopause: a randomized controlled trial. Obstet Gynecol 2006;108:1402-10.

Cognition

Joffe H, Hall JE, Gruber S, Sarmiento IA, Cohen LS, Yurgelun-Todd D, Martin KA. Estrogen therapy selectively enhances prefrontal cognitive processes: a randomized, double-blind, placebo-controlled study with functional magnetic resonance imaging in perimenopausal and recently postmenopausal women. Menopause 2006;13:411-22.

Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JE, Gass ML, Stefanick ML, Lane DS, Hays J, Johnson KC, Coker LH, Dailey M, Bowen D. 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;289:2663-72.

Shumaker SA, Legault C, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN, 3rd, Assaf AR, Jackson RD, Morley Kotchen J, Wassertheil-Smoller S, Wactawski-Wende J. 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;289:2651-62.

Hormonal Therapy

Amended Report from the North American Menopause Society Advisory Panel on Postpmenopausal Hormone Therapy.

Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O’Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 2004;291:1701-12.

Ettinger B. Rationale for use of lower estrogen doses for postmenopausal hormone therapy. Maturitas 2007.

Gass M. Impact of WHI conclusions and ACOG guidelines on clinical practice. Int J Fertil Womens Med. 2003 May-Jun;48(3):106-10; discussion 137-8.

Grady D. Postmenopausal hormones–therapy for symptoms only. N Engl J Med. 2003 May 8;348(19):1835-7. Epub 2003 Mar 17.

Grady D, Ettinger B, Tosteson AN, Pressman A, Macer JL. Predictors of difficulty when discontinuing postmenopausal hormone therapy. Obstet Gynecol 2003;102:1233-9.

Hays J, Ockene JK, et al; Women’s Health Initiative Investigators. Effects of Estrogen plus Progestin on Health-Related Quality of Life. N Engl J Med 2003 May 8;348(19):1839-54.

Langenberg P, Kjerulff KH, Stolley PD. Hormone replacement and menopausal symptoms following hysterectomy. Am J Epidemiol 1997;146:870-80.

McIntyre RS, Konarski JZ, Grigoriadis S, Fan NC, Mancini DA, Fulton KA, Stewart DE, Kennedy SH. Hormone replacement therapy and antidepressant prescription patterns: a reciprocal relationship. CMAJ 2005;172:57-9.

Nelson HD, Humphrey LL, et al. Postmenopausal Hormone Replacement Therapy: Scientific Review. JAMA 2002; 288:872-881.

Ockene JK, Barad DH, Cochrane BB, Larson JC, Gass M, Wassertheil-Smoller S, Manson JE, Barnabei VM, Lane DS, Brzyski RG, Rosal MC, Wylie-Rosett J, Hays J. Symptom experience after discontinuing use of estrogen plus progestin. JAMA 2005;294:183-93.

Rossouw JE, Anderson GL, et al; 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.

Shulman LP, Harari D. Low-dose transdermal estradiol for symptomatic perimenopause. Menopause 2004;11:34-9.

Simon JA, Mack CJ. Counseling patients who elect to discontinue hormone therapy. Int J Fertil Womens Med. 2003 May-Jun;48(3):111-6; discussion 137-8.

Stefanick ML. Estrogens and progestins: background and history, trends in use, and guidelines and regimens approved by the US Food and Drug Administration. Am J Med 2005;118 Suppl 12B:64-73.

WebMD Article: “Managing Menopause: What to Do? Hormone Replacement Therapy May Be OK Short Term.

Special Considerations for Breast Cancer Patients

New! Bankhead C. ASCO Breast: Hot flash therapy plus hypnotic improves sleep in breast cancer patients. Coverage of ASCO Breast Cancer Symposium with presenter Hadine Joffe, M.D., M.Sc. September 9, 2008.

Couzi RJ, Helzlsouer KJ, Fetting JH. Prevalence of menopausal symptoms among women with a history of breast cancer and attitudes toward estrogen replacement therapy. J Clin Oncol 1995;13:2737-44.

Mom CH, Buijs C, Willemse PH, Mourits MJ, de Vries EG. Hot flushes in breast cancer patients. Crit Rev Oncol Hematol 2006;57:63-77.