Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Psychiatry Reports
Published in: Current Psychiatry Reports 12/2014

01-12-2014 | Women’s Mental Health (D Rubinow, Section Editor)

Hormone Replacement Therapy in the Treatment of Perimenopausal Depression

Authors: Jennifer L. Gordon, Susan S. Girdler

Published in: Current Psychiatry Reports | Issue 12/2014

Login to get access

Abstract

The menopause transition is associated with a two to fourfold increased risk in major depressive disorder (MDD) and clinical elevations in depressive symptoms. While the pathophysiological mechanisms underlying this increased risk remain uncertain, ovarian hormone fluctuation is believed to play a role. To the extent that this is the case, hormone replacement therapy (HRT), through its hormone-stabilizing effects, represents a viable antidepressant treatment. The current review summarizes the most recent literature evaluating the efficacy of HRT in treating MDD in peri- and postmenopausal women. In addition, to provide a clinical context in which to interpret this research, the endocrinology and clinical phenomenology related to depression with onset in the menopause transition (D-MT) are discussed. The available evidence suggests that HRT, specifically involving estrogen delivered through a skin patch, is a promising intervention in the treatment of D-MT. However, HRT of any form is an ineffective antidepressant in women who are well into the postmenopausal period.
Literature
1.
Hale GE, Robertson DM, Burger HG. The perimenopausal woman: endocrinology and management. J Steroid Biochem Mol Biol. 2014;142(7):121–31.PubMedCrossRef
2.
Santoro N, Randolph Jr JF. Reproductive hormones and the menopause transition. Obstet Gynecol Clin N Am. 2011;38(3):455.CrossRef
3.
Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary of the Stages of Reproductive Aging Workshop+10: addressing the unfinished agenda of staging reproductive aging. Climacteric. 2012;15(2):105–14.PubMedCentralPubMedCrossRef
4.
Tepper PG, Randolph Jr JF, McConnell DS, Crawford SL, El Khoudary SR, Joffe H, et al. Trajectory clustering of estradiol and follicle-stimulating hormone during the menopausal transition among women in the Study of Women’s Health Across the Nation (SWAN). J Clin Endocrinol Metab. 2012;97(8):2872–80.PubMedCentralPubMedCrossRef
5.
McKinlay SM, Brambilla DJ, Posner JG. The normal menopause transition. Maturitas. 1992;14(2):103–15.PubMedCrossRef
6.
Bromberger JT, Matthews KA, Schott LL, Brockwell S, Avis NE, Kravitz HM, et al. Depressive symptoms during the menopausal transition: the Study of Women’s Health Across the Nation (SWAN). J Affect Disord. 2007;103(1):267–72.PubMedCentralPubMedCrossRef
7.
Woods NF, Smith-DiJulio K, Percival DB, Tao EY, Mariella A, Mitchell ES. Depressed mood during the menopausal transition and early postmenopause: observations from the Seattle midlife women’s health study. Menopause. 2008;15(2):223–32.PubMedCrossRef
8.
Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006;63(4):375.PubMedCrossRef
9.
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;63(4):385.PubMedCrossRef
10.
Bromberger JT, Kravitz HM, Chang Y-F, Cyranowski JM, Brown C, Matthews KA. Major depression during and after the menopausal transition: Study of Women’s Health Across the Nation (SWAN). Psychol Med. 2011;41(9):1879–88.PubMedCentralPubMedCrossRef
11.
Bromberger J, Kravitz H, Matthews K, Youk A, Brown C, Feng W. Predictors of first lifetime episodes of major depression in midlife women. Psychol Med. 2009;39(1):55.PubMedCentralPubMedCrossRef
12.
National Institutes of Health. National Institutes of Health State-of-the-Science Conference statement: management of menopause-related symptoms. Ann Intern Med. 2005;142(12 Pt 1):1003.
13.
Thurston RC, Blumenthal JA, Babyak MA, Sherwood A. Emotional antecedents of hot flashes during daily life. Psychosom Med. 2005;67(1):137–46.PubMedCrossRef
14.
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(1):62.PubMedCrossRef
15.
Avis NE, Crawford S, Stellato R, Longcope C. Longitudinal study of hormone levels and depression among women transitioning through menopause. Climacteric. 2001;4(3):243–9.PubMedCrossRef
16.
Daly RC, Danaceau MA, Rubinow DR, Schmidt PJ. Concordant restoration of ovarian function and mood in perimenopausal depression. Am J Psychiatr. 2003;160(10):1842–6.PubMedCrossRef
17.
Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR. Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatr. 2000;157(6):924–30.PubMedCrossRef
18.
Schmidt PJ, Nieman LK, Danaceau MA, Adams LF, Rubinow DR. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. N Engl J Med. 1998;338(4):209–16.PubMedCrossRef
19.
De Leo V, Lanzetta D, Morgante G, De Palma P, D’Antona D. Inhibition of ovulation with transdermal estradiol and oral progestogens in perimenopausal women. Contraception. 1997;55(4):239–43.PubMedCrossRef
20.
Girdler SS, Hinderliter AL, Wells EC, Sherwood A, Grewen KM, Light KC. Transdermal versus oral estrogen therapy in postmenopausal smokers: hemodynamic and endothelial effects. Obstet Gynecol. 2004;103(1):169–80.PubMedCrossRef
21.
Bukulmez O, Al A, Gurdal H, Yarali H, Ulug B, Gurgan T. Short-term effects of three continuous hormone replacement therapy regimens on platelet tritiated imipramine binding and mood scores: a prospective randomized trial. Fertil Steril. 2001;75(4):737–43.PubMedCrossRef
22.
Ross L, Alder E, Cawood RH, Brown J, Gebbie AE. Psychological effects of hormone replacement therapy: a comparison of tibolone and a sequential estrogen therapy. J Psychosom Obstet Gynecol. 1999;20(2):88–96.CrossRef
23.
Soares CN, Arsenio H, Joffe H, Bankier B, Cassano P, Petrillo LF, et al. 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(5):780–6.PubMedCrossRef
24.
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 Psychiatr. 2003;160(8):1519–22.PubMedCrossRef
25.
de Novaes SC, 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(6):529.CrossRef
26.•
Schmidt PJ, Nieman L, Danaceau MA, Tobin MB, Roca CA, Murphy JH, et al. Estrogen replacement in perimenopause-related depression: a preliminary report. Am J Obstet Gynecol. 2000;183(2):414–20. This position statement provides an excellent summary of our current understanding of the risks and benefits of HRT in relation to health and disease.PubMedCrossRef
27.
Joffe H, Petrillo LF, Koukopoulos A, Viguera AC, Hirschberg A, Nonacs R, et al. Increased estradiol and improved sleep, but not hot flashes, predict enhanced mood during the menopausal transition. J Clin Endocrinol Metab. 2011;96(7):E1044–54.PubMedCentralPubMedCrossRef
28.•
Joffe H, Hall JE, Gruber S, Sarmiento IA, Cohen LS, Yurgelun-Todd D, et al. 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(3):411–22. This manuscript describes the most recent RCT of transdermal estradiol in the treatment of depression in peri- and early postmenopausal women.PubMedCrossRef
29.•
Rogines-Velo MP, Heberle AE, Joffe H. Effect of medroxyprogesterone on depressive symptoms in depressed and non-depressed perimenopausal and postmenopausal women following discontinuation of transdermal estradiol therapy. Menopause. 2012;19(4):471. This is the most recent study examining the mood effects of P4 supplementation and one of the few that includes depressed women.PubMedCentralPubMedCrossRef
30.
Yalamanchili V, Gallagher JC. Treatment with hormone therapy and calcitriol did not affect depression in elderly postmenopausal women: no interaction with estrogen and vitamin D receptor genotype polymorphisms. Menopause. 2012;19(6):697.PubMedCentralPubMedCrossRef
31.
Demetrio FN, Rennó Jr J, Gianfaldoni A, Gonçalves M, Halbe HW, Filho AH, et al. Effect of estrogen replacement therapy on symptoms of depression and anxiety in non-depressive menopausal women. Arch Women’s Ment Health. 2011;14(6):479–86.CrossRef
32.
Morrison MF, Kallan MJ, Ten Have T, Katz I, Tweedy K, Battistini M. Lack of efficacy of estradiol for depression in postmenopausal women: a randomized, controlled trial. Biol Psychiatry. 2004;55(4):406–12.PubMedCrossRef
33.
Kornstein SG, Toups M, Rush AJ, Wisniewski SR, Thase ME, Luther J, et al. Do menopausal status and use of hormone therapy affect antidepressant treatment response? Findings from the sequenced treatment alternatives to relieve depression (STAR*D) study. J Women’s Health. 2013;22(2):121–31.CrossRef
34.
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. J Am Med Assoc. 2002;288(3):321–33.CrossRef
35.
Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the women’s health initiative randomized trial. J Am Med Assoc. 2003;289(24):3243–53.CrossRef
36.
Schmidt P. The 2012 hormone therapy position statement of the North American Menopause Society. Menopause. 2012;19(3):257.PubMedCentral
37.
Santen RJ, Allred DC, Ardoin SP, Archer DF, Boyd N, Braunstein GD, et al. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab. 2010;95(7 supplement 1):s1–66.PubMedCrossRef
38.
Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. J Am Med Assoc. 2007;297(13):1465–77.CrossRef
39.
Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD, Hsia J, et al. Estrogen therapy and coronary-artery calcification. N Engl J Med. 2007;356(25):2591–602.PubMedCrossRef
40.
Canonico M, Oger E, Plu-Bureau G, Conard J, Meyer G, Lévesque H, et al. Hormone therapy and venous thromboembolism among postmenopausal women impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation. 2007;115(7):840–5.PubMedCrossRef
41.
Smith NL, Blondon M, Wiggins KL, Harrington LB, van Hylckama VA, Floyd JS, et al. Lower risk of cardiovascular events in postmenopausal women taking oral estradiol compared with oral conjugated equine estrogens. JAMA Intern Med. 2014;174(1):25–31.PubMedCrossRef
42.
L’hermite M. HRT optimization, using transdermal estradiol plus micronized progesterone, a safer HRT. Climacteric. 2013;16(S1):44–53.PubMedCrossRef
43.
Adams MR, Register TC, Golden DL, Wagner JD, Williams JK. Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary artery atherosclerosis. Arterioscler Thromb Vasc Biol. 1997;17(1):217–21.PubMedCrossRef
44.
Goodman MP. Are all estrogens created equal? A review of oral vs. transdermal therapy. J Women’s Health. 2012;21(2):161–9.CrossRef
45.•
Wharton W, Gleason CE, Miller VM, Asthana S. Rationale and design of the Kronos Early Estrogen Prevention Study (KEEPS) and the KEEPS Cognitive and Affective sub study (KEEPS Cog). Brain Res. 2013;1514:12–7. This manuscript summarizes the rationale and design of the cognitive and affective substudy of the Kronos Early Estrogen Prevention Study (KEEPS Cog), an RCT evaluating the mood benefits of conjugated equine estrogen and transdermal estradiol. In doing so, it summarizes many of the key issues that are currently of interest in the field of perimenopausal depression treatment.PubMedCentralPubMedCrossRef
Metadata
Title
Hormone Replacement Therapy in the Treatment of Perimenopausal Depression
Authors
Jennifer L. Gordon
Susan S. Girdler
Publication date
01-12-2014
Publisher
Springer US
Published in
Current Psychiatry Reports / Issue 12/2014
Print ISSN: 1523-3812
Electronic ISSN: 1535-1645
DOI
https://doi.org/10.1007/s11920-014-0517-1

Other articles of this Issue 12/2014

Current Psychiatry Reports 12/2014 Go to the issue

Genetic Disorders (W Berrettini, Section Editor)

Genetics of Alcoholism

Sleep Disorders (P Gehrman, Section Editor)

Wake-Promoting Pharmacotherapy for Psychiatric Disorders

Bipolar Disorders (W Coryell, Section Editor)

Current State of Biomarkers in Bipolar Disorder

Psychiatry in the Digital Age (JS Luo, Section Editor)

Professional Social Networking

Psychiatry in the Digital Age (JS Luo, Section Editor)

The Use of Electronic Games in Therapy: a Review with Clinical Implications

Mood Disorders (JF Greden, Section Editor)

Population-Based Initiatives in College Mental Health: Students Helping Students to Overcome Obstacles