This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (78)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Women's Health  • Women's Health, Other  • Randomized Controlled Trial  • Depression  • Alert me on articles by topic

A Double-blind, Randomized, Placebo-Controlled Trial

Cláudio de Novaes Soares, MD, PhD; Osvaldo P. Almeida, MD, PhD; Hadine Joffe, MD; Lee S. Cohen, MD

Arch Gen Psychiatry. 2001;58:529-534.

Background  Results of previous studies suggest that estrogen improves somatic and mild depressive symptoms experienced by perimenopausal women. This study investigated the efficacy of 17ß-estradiol for the treatment of clinically significant depressive disorders in endocrinologically confirmed perimenopausal women.

Methods  Perimenopausal women (aged 40-55 years, with irregular menstrual periods and serum concentrations of follicle-stimulating hormone >25 IU/L), meeting criteria for major depressive disorder, dysthymic disorder, or minor depressive disorder, according to DSM-IV, were randomized to receive transdermal patches of 17ß-estradiol (100 µg) or placebo in a 12-week, double-blind, placebo-controlled study. A 4-week washout period followed the 12-week treatment phase. Outcome measures were the Montgomery-Åsberg Depression Rating Scale and Blatt-Kupperman Menopausal Index scores.

Results  Fifty women were enrolled in the study; 26 met DSM-IV criteria for major depressive disorder, 11 for dysthymic disorder, and 13 for minor depressive disorder. Remission of depression was observed in 17 (68%) women treated with 17ß-estradiol compared with 5 (20%) in the placebo group (P = .001). Subjects responded similarly to estradiol treatment, regardless of DSM-IV diagnosis. Patients treated with estradiol sustained antidepressant benefit of treatment after the 4-week washout period, although somatic complaints increased in frequency and intensity. Treatment was well tolerated and adverse events were rare in both groups.

Conclusion  Transdermal estradiol replacement is an effective treatment of depression for perimenopausal women.

From the Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil (Dr Soares); the Department of Psychiatry and Behavioral Science, University of Western Australia, Perth (Dr Almeida); and Perinatal and Reproductive Psychiatry Clinical Research Program, Massachusetts General Hospital, Harvard Medical School, Boston (Drs Soares, Joffe, and Cohen).

Corresponding author: Cláudio de Novaes Soares, MD, PhD, Perinatal and Reproductive Psychiatry Clinical Research Program, Massachusetts General Hospital, Harvard Medical School, 15 Parkman St, WACC 812, Boston, MA 02114 (e-mail: csoares{at}partners.org).

RELATED ARTICLE

Sex and Psychopharmacology: Is Natural Estrogen a Psychotropic Drug in Women?
Stephen M. Stahl
Arch Gen Psychiatry. 2001;58(6):537-538.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Estrogen in Severe Mental Illness: A Potential New Treatment Approach
Kulkarni et al.
Arch Gen Psychiatry 2008;65:955-960.
ABSTRACT | FULL TEXT  

Low Free Testosterone Concentration as a Potentially Treatable Cause of Depressive Symptoms in Older Men
Almeida et al.
Arch Gen Psychiatry 2008;65:283-289.
ABSTRACT | FULL TEXT  

The Effects of Estradiol on Central Serotonergic Systems and Its Relationship to Mood in Women
Lasiuk and Hegadoren
Biol Res Nurs 2007;9:147-160.
ABSTRACT  

Depressive Disorders Related to Female Reproductive Transitions
Serrano and Warnock
Journal of Pharmacy Practice 2007;20:385-391.
ABSTRACT  

The resistance to depressive relapse in menopausal women undergoing tryptophan depletion: preliminary findings
Epperson et al.
J Psychopharmacol 2007;21:414-420.
ABSTRACT  

Blinded trials taken to the test: an analysis of randomized clinical trials that report tests for the success of blinding
Hrobjartsson et al.
Int J Epidemiol 2007;36:654-663.
ABSTRACT | FULL TEXT  

Body Mass Index and Risk of Suicide Among Men
Mukamal et al.
Arch Intern Med 2007;167:468-475.
ABSTRACT | FULL TEXT  

Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women
Morrison et al.
J. Neurosci. 2006;26:10332-10348.
FULL TEXT  

Augmentation and combination strategies for depression.
DeBattista
J Psychopharmacol 2006;20:11-18.
ABSTRACT  

Associations of hormones and menopausal status with depressed mood in women with no history of depression.
Freeman et al.
Arch Gen Psychiatry 2006;63:375-382.
ABSTRACT | FULL TEXT  

Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles.
Cohen et al.
Arch Gen Psychiatry 2006;63:385-390.
ABSTRACT | FULL TEXT  

Premenstrual Symptoms and Perimenopausal Depression
Richards et al.
Am. J. Psychiatry 2006;163:133-137.
ABSTRACT | FULL TEXT  

Duloxetine for the Treatment of Major Depressive Disorder in Women Ages 40 to 55 Years
Burt et al.
Psychosomatics 2005;46:345-354.
ABSTRACT | FULL TEXT  

Depression, the Perimenopause, and Estrogen Therapy
SCHMIDT
Ann. N. Y. Acad. Sci. 2005;1052:27-40.
ABSTRACT | FULL TEXT  

Perimenopause and Sexual Functioning: Implications for Therapists
Cobia and Harper
The Family Journal 2005;13:226-231.
ABSTRACT  

Effect of Estrogen-Serotonin Interactions on Mood and Cognition
Amin et al.
Behav Cogn Neurosci Rev 2005;4:43-58.
ABSTRACT  

Association Between Physiological Serum Concentration of Estrogen and the Mental Health of Community-Dwelling Postmenopausal Women Age 70 Years and Over
Almeida et al.
AJGP 2005;13:142-149.
ABSTRACT | FULL TEXT  

Hormone replacement therapy and antidepressant prescription patterns: a reciprocal relationship
McIntyre et al.
CMAJ 2005;172:57-59.
FULL TEXT  

Guideline Watch: Practice Guideline for the Treatment of Patients With Major Depressive Disorder, 2nd Edition
Fochtmann and Gelenberg
Focus 2005;3:34-42.
FULL TEXT  

A Longitudinal Evaluation of the Relationship Between Reproductive Status and Mood in Perimenopausal Women
Schmidt et al.
Am. J. Psychiatry 2004;161:2238-2244.
ABSTRACT | FULL TEXT  

Depression, Estrogen, and the Women's Health Initiative
Stewart et al.
Psychosomatics 2004;45:445-447.
ABSTRACT | FULL TEXT  

Depression
Obstet Gynecol 2004;104:49S-55S.
FULL TEXT  

Depression increases in women during early to late menopause but decreases after menopause
Bosworth
Evid. Based Ment. Health 2004;7:90-90.
FULL TEXT  

Postmenopausal Estrogen for Treatment of Hot Flashes: Clinical Applications
Nelson
JAMA 2004;291:1621-1625.
ABSTRACT | FULL TEXT  

Hormones and Menopausal Status as Predictors of Depression in Women in Transition to Menopause
Freeman et al.
Arch Gen Psychiatry 2004;61:62-70.
ABSTRACT | FULL TEXT  

In Vivo Effects of Estrogen on Human Brain
CUTTER et al.
Ann. N. Y. Acad. Sci. 2003;1007:79-88.
ABSTRACT | FULL TEXT  

Concordant Restoration of Ovarian Function and Mood in Perimenopausal Depression
Daly et al.
Am. J. Psychiatry 2003;160:1842-1846.
ABSTRACT | FULL TEXT  

Short-Term Use of Estradiol for Depression in Perimenopausal and Postmenopausal Women: A Preliminary Report
Cohen et al.
Am. J. Psychiatry 2003;160:1519-1522.
ABSTRACT | FULL TEXT  

Oestrogen, brain function, and neuropsychiatric disorders
Cutter et al.
J. Neurol. Neurosurg. Psychiatry 2003;74:837-840.
FULL TEXT  

An Integrative Approach to Depression: Part 2--Assessment and Treatment
Zuess
Complementary Health Practice Review 2003;8:99-115.
ABSTRACT  

Update in Women's Health
Freund et al.
ANN INTERN MED 2003;138:119-127.
FULL TEXT  

OTHER ARTICLES NOTED (Nov 01 to 18 Oct 02)
Evid. Based Nurs. 2003;6:e1-1.
FULL TEXT  

Combination Therapy in the Treatment of Major Depressive Disorder Complicated by Fibromyalgia and Menopause
Clayton and Kaltsounis-Puckett
Psychosomatics 2002;43:491-493.
FULL TEXT  

Update in Psychiatry
Schneider and Levenson
ANN INTERN MED 2002;137:671-677.
FULL TEXT  

Other Articles Noted
Evid. Based Ment. Health 2002;5:8-8.
FULL TEXT  

17{beta}-estradiol reduced depressive and somatic symptoms in perimenopausal women
Thacker
Evid. Based Med. 2002;7:21-21.
FULL TEXT  

Estradiol for Depression?
JWatch Women's Health 2001;2001:6-6.
FULL TEXT  

Is Estrogen an Antidepressant?
JWatch Psychiatry 2001;2001:2-2.
FULL TEXT  

Estrogen for Depression in Menopausal Women
JWatch General 2001;2001:6-6.
FULL TEXT  

Increased anxiety and synaptic plasticity in estrogen receptor beta -deficient mice
Krezel et al.
Proc. Natl. Acad. Sci. USA 2001;98:12278-12282.
ABSTRACT | FULL TEXT