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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Menopause. Author manuscript; available in PMC 2011 July 1.
Published in final edited form as:
PMCID: PMC2949279
NIHMSID: NIHMS198665

The Influence of Menopausal Status and Postmenopausal Use of Hormone Therapy on Presentation of Major Depression in Women

Abstract

Objective:

The purpose of this study was to determine whether there are differences in depression characteristics among premenopausal, perimenopausal, and postmenopausal women with major depressive disorder. This study also evaluated these differences between postmenopausal women with major depressive disorder who are taking and not taking hormone therapy.

Methods:

Analyses conducted with data from the Sequenced Treatment Alternatives to Relieve Depression study focused on female outpatients with non-psychotic major depressive disorder seeking treatment in 41 primary or psychiatric care settings across the United States. Baseline demographic and clinical characteristics were compared among women not taking hormone therapy who were premenopausal (N=950), perimenopausal (N=380), or postmenopausal (N=562). These comparisons were also made between postmenopausal women (n=768) taking (N=171) or not taking (N=562) hormone therapy.

Results:

After adjusting for sociodemographic and clinical baseline differences, premenopausal women were more likely to present with irritability than either peri- or postmenopausal women, and were more likely to have decreased appetite and less likely to have early morning insomnia than perimenopausal women. Postmenopausal women were more likely to have suicidal ideation and poorer physical functioning than either of the other groups, and were more likely to have sympathetic arousal and gastrointestinal symptoms than premenopausal women. After adjusting for baseline differences, postmenopausal women taking hormone therapy had better physical functioning, fewer melancholic features, less sympathetic arousal, and more lack of involvement in activities than women not taking hormone therapy.

Conclusions:

Menopausal status and postmenopausal use of hormone therapy may influence the clinical presentation of major depressive episodes in women.

Keywords: menopause, hormone therapy, depression, major depressive disorder

INTRODUCTION

The sex difference in prevalence of major depressive disorder (MDD) is well established, with rates about twice as high in women than in men.1-3 A number of studies have also demonstrated differences in the clinical presentation of MDD in women versus men, including presenting symptoms, course of illness features, comorbidity, and functional impairment. 4-8 Moreover, sex differences in treatment response, both to antidepressants and psychotherapy, have been reported in some but not all studies.4,9-16

Reproductive hormonal factors are likely to contribute to the sex differences in depression, which begin around the time of puberty and persist through midlife.2,17 Some women appear to be particularly susceptible to developing depression during times of hormonal fluctuation, including the premenstrual phase of the menstrual cycle, the postpartum period, and the perimenopause.18-20 Fluctuations in estrogen and progesterone are known to affect neurotransmitters involved in depression, including both serotonin and norepinephrine.21,22 In addition, some studies have suggested that menopausal status may influence antidepressant treatment response, particularly with tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs).9,11,12,14,15,23

Despite the clear influences of hormonal factors on depression in some women, to the best of our knowledge, no study has examined whether the clinical presentation of depression in women differs according to their menopausal status. Further, no study has assessed the possible effects of hormone therapy on the characteristics of depression in postmenopausal women. A recent report24 did find that hormonal contraceptives may affect depression severity and symptom profile in premenopausal women. Moreover, several studies have found that estrogen is efficacious in treating perimenopausal depression.25-27 Others have suggested that hormonal therapy may enhance antidepressant treatment response in postmenopausal women who are treated with SSRIs.15,28-30 Hence, postmenopausal women with depression who are taking hormone therapy may present differently than those who are not.

The purpose of this report was to determine whether the presentation of depression in women differs according to menopausal status or the presence/absence of hormone therapy. To determine the former, we compared baseline sociodemographic and clinical characteristics among premenopausal, perimenopausal, and postmenopausal women with MDD who were not taking hormone therapy. To determine the latter, we evaluated differences in depression characteristics in postmenopausal women who were and were not taking hormone therapy.

METHODS

The current study used data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study,31,32 a National Institute of Mental Health (NIMH)-supported study that provided an opportunity to examine differences in the presentation of depression as a function of menopausal status in women seeking treatment for a major depressive episode. The goal of STAR*D was to define prospectively which of several treatments are most effective for participants with non-psychotic MDD and who report an unsatisfactory clinical outcome to an initial, and if necessary, subsequent treatment(s). The study protocol was developed according to the principles of the Declaration of Helsinki. All risks, benefits, and adverse events associated with STAR*D were explained to participants, who provided written informed consent prior to study participation. The population and methods of STAR*D are described in detail elsewhere.31,32

Study Population

STAR*D enrolled 4041 participants from July 2001 through April 2004. To achieve the goal of recruiting a broadly representative group of participants with MDD, STAR*D enrolled patients from 18 primary and 23 psychiatric care clinical sites across the United States that serve either the public or private sectors. Advertising for participants was not permitted as it tends to enroll a less representative study sample.33 Every effort was made to recruit a broad spectrum of participants representing all racial groups and both sexes.

Inclusion/Exclusion Criteria

The inclusion criteria were broad so as to acquire a sample representative of individuals with MDD who would receive medication or psychotherapy in everyday practice. Eligible participants were outpatients aged 18–75 with non-psychotic MDD who scored ≥14 on the 17-Item Hamilton Rating Scale for Depression34,35 (HRSD17) and for whom antidepressant treatment was deemed appropriate by the treating clinician. Participants with suicidal ideation were eligible, as long as outpatient treatment was deemed clinically safe. Participants with most general medical conditions (GMCs) were eligible; however, persons with medical contraindications that precluded randomization to treatments used in the first two steps of the study were excluded.

Participants with a lifetime history of schizophrenia, schizoaffective or bipolar disorder, or MDD with psychotic features were excluded, as were those with a primary diagnosis of anorexia nervosa, bulimia, or obsessive-compulsive disorder because these primary psychiatric conditions required a different initial treatment.36 Participants with currently active and clinically significant substance abuse were eligible, as long as in-patient care was not required clinically at study entry. Those with active substance dependence who required detoxification were not eligible for reasons of medical safety. Participants with severe, unstable concurrent psychiatric conditions likely to require hospitalization within six months of study entry were also ineligible.

Participants were excluded if they had an established, well-documented history of non-response or clear intolerability in the current major depressive episode to one or more of the protocol treatments delivered at an adequate dose. Participants taking concomitant anxiolytics or sedative hypnotics could enter the study as long as their clinician determined that the antidepressant treatments in the protocol were appropriate and safe. Participants were excluded if they were currently receiving a targeted psychotherapy aimed at their depression; they could participate if they had not responded to such psychotherapy and subsequently terminated it prior to study enrollment, or if they were receiving counseling or therapy for other problems. Participants who were breastfeeding, pregnant or intended to become pregnant within nine months of enrollment were also excluded.

Assessments

Clinical Research Coordinators (CRCs) at each of 14 Regional Centers were trained and certified in implementing the treatment protocol and in data collection methods. After obtaining written informed consent at the screening/baseline visit, participants were evaluated by the CRC. Sociodemographic and clinical information was collected, as was prior course of illness, current and past substance abuse, prior suicide attempts, current GMCs, and prior history of treatment in the current major depressive episode. The CRC completed the HRSD17 (at baseline to establish inclusion/exclusion criteria) and the Quick Inventory of Depressive Symptomatology — Clinician-rated37-38 (QIDS-C16). Current GMCs were assessed using the Cumulative Illness Rating Scale39-41 (CIRS), and the presence or absence of 11 Axis I psychiatric disorders was assessed using the Psychiatric Diagnostic Screening Questionnaire (PDSQ).42,43 A Research Outcomes Assessor called participants for a telephone interview within 72 hours of the baseline visit to complete the HRSD17 and the 30-item Inventory of Depressive Symptomatology–Clinician-rated (IDS-C30).38,44 Also within 72 hours of enrollment, a telephonic Interactive Voice Response (IVR) system was used to collect the 16-item Quick Inventory of Depressive Symptomatology – Self-Rated37,38 (QIDS-SR16) for assessment of depression severity, and the following measures of quality of life and functioning: the 12-item Short-Form Health Survey45 (SF-12), the 16-item Quality of Life Enjoyment and Satisfaction Questionnaire46 (Q-LES-Q), and the five-item Work and Social Adjustment Scale47 (WSAS).

Group Assignment / Definition of Menopausal Status

Menopausal status was determined based on both current age and the participant's response to the following question: “Is the patient postmenopausal or post-hysterectomy, or male?” A woman was classified as premenopausal if she was younger than 40 years of age. Of those classified as premenopausal, 49 (4.74 %) answered “yes” to the above question (indicating that they were postmenopausal or post-hysterectomy). These women were still included in the premenopausal group due to the very low prevalence (1-2%) of naturally occurring menopause in women under 40 years old. Those in this age group who were post-hysterectomy but still had ovaries were likely to still be premenopausal, and those who also had both ovaries removed were likely to be taking menopausal hormone therapy and would thus be excluded from the analyses. Women who were at least 40 years old and who reported not being postmenopausal or post-hysterectomy were classified as perimenopausal. Finally, women who were at least 40 years old and reported being postmenopausal or post-hysterectomy were operationally defined as postmenopausal. A small number of these women may have had a hysterectomy without ovariectomy and were still cycling. Women who had either experienced natural menopause or had undergone a hysterectomy were included in the study, with the exception of those women on hormone therapy.

Of the 4041 participants enrolled, 62.7% were women (N=2532). Because administration of hormonal therapies such as hormonal contraceptives and menopausal hormone therapy could affect the presentation of depressive and menopausal symptoms, women taking these medications (N=636 women; 71 progesterone, 147 estrogen, 302 combination, 116 unknown/other) were excluded from the analyses comparing premenopausal, perimenopausal, and postmenopausal women. Of the remaining 1896 women, four were excluded due to missing information about age or menopausal status. Thus, the analyses regarding menopausal status were conducted with a sample of 1890 women. Of these, 950 (50.1%) were classified as premenopausal, 380 (20.0%) were classified as perimenopausal, and 562 (29.6%) were classified as postmenopausal (Figure 1a).

Figure 1
Consort Chart

Regarding the comparison with postmenopausal women by hormone therapy status, of the total number of eligible women enrolled in STAR*D (N=2532), 768 were postmenopausal. Of these, 35 (4.5%) could not be classified into either group. Thus the analyses regarding hormone therapy status were conducted with a sample of 737 postmenopausal women. Of these, 171 (22.3%) were taking hormone therapy and 562 (73.2%) were not taking hormone therapy (Figure 1b).

Statistical Analyses

Descriptive statistics are presented as percentages for categorical variables and as means and standard deviations for continuous variables. Chi-square tests and both parametric and nonparametric analysis of variance methods were used to compare the distribution of discrete and continuous, respectively, sociodemographic and clinical characteristics across menopausal status. After adjusting for baseline sociodemographic and clinical characteristics that differed across menopausal status, regression models (linear for continuous measures and logistic regression for binary measures) were used to assess the independent effect of menopausal status on symptom severity, depressive features, functioning, quality of life, and presence of psychiatric comorbidities and the significance level from a likelihood ratio test is presenteed. If significant differences were identified after adjustment, post-hoc comparisons were made using a Bonferroni correction.

Chi-square tests and both parametric and nonparametric analysis of variance methods were similarly used to compare the distribution of discrete sociodemographic and clinical characteristics across those women taking and not taking hormone therapy. After adjusting for baseline sociodemographic and clinical characteristics that differed across menopausal status, regression models (linear for continuous measures and logistic regression for binary measures) were used to assess the independent effect of hormone therapy on symptom severity, depressive features, quality of life, functioning, presence of depressive symptoms and presence of psychiatric comorbidities, with menopausal status entered into the model as a two-level design variable. A p-value < .05 indicated a significant difference in all analyses except for the post-hoc analyses, for which a p-value of < .0167 indicated a significant difference.

RESULTS

Sociodemographic and Baseline Characteristics

Table 1 shows the sociodemographic and baseline clinical characteristics of the study sample by menopausal status. Most of the postmenopausal women were seen in primary care settings, while the majority of the premenopausal and perimenopausal women were seen in psychiatric care settings. The average ages of premenopausal, perimenopausal and postmenopausal women were 29.4±5.9 years, 45.0±4.0 years and 54.6±7.9 years, respectively.

Table 1
Demographic and Baseline Characteristics by Menopausal Status

Several characteristics of depression history differentiated the three menopausal status groups. Specifically, premenopausal and perimenopausal women were more likely to have a positive family history of depression (Pre: 58%, Peri: 63%, Post: 51%, p=.0008) and were approximately twice as likely to report a past suicide attempt than postmenopausal women (Pre: 23%, Peri: 20%, Post: 12%, p<.0001). Premenopausal women had the youngest age of onset of their first depressive episode and postmenopausal women had the oldest age of onset (Pre: 19.0 (87.9), Peri: 26.6 (13.4), Post: 35.1 (17.8), p<.0001). Postmenopausal women were most likely to present with a chronic depressive episode (Pre: 21%, Peri: 26%, Post: 37%, p<.0001), had the longest duration of depressive illness (Pre: 10.5 (8.0), Peri: 18.4 (13.2), Post: 19.6 (16.3), p<.0001), and had the greatest medical comorbidity based on the CIRS (Pre: 2.2 (1.9), Peri: 3.1 (2.1), Post: 3.9 (2.4), p<.0001).

Depression Severity, Subtype, and Level of Functioning

With regard to symptom severity (Table 2), no differences were found among the menopausal status groups in total scores on either the HRSD17 (Pre: 2.06 (6.5), Peri: 20.1 (6.5), Post: 20.4 (6.7), p=.4763) or the IDS-C30 (Pre: 37.4 (11.3), Peri: 36.0 (11.6), Post: 36.6 (12.1), p=.1311). Total scores on the QIDS-SR16 differed slightly but significantly as a function of menopausal status, with premenopausal women demonstrating the highest mean score of the three groups (Pre: 16.4 (4.2), Peri: 15.5 (4.4), Post: 15.8 (4.3), p=.0008). Postmenopausal women were the most likely to present with anxious features (Pre: 48%, Peri: 44%, Post: 55%, p=.0057). The differences found in QIDS-SR16 scores and anxious features were no longer statistically significant after adjustment for differences in baseline sociodemographic and clinical characteristics. Postmenopausal women showed higher mental (Pre: 24.7 (8.2), Peri: 26.0 (8.7), Post: 28.8 (9.2), p<.0001) and lower physical (Pre: 52.0 (10.3), Peri: 49.9 (11.9), Post: 43.4 (11.9), p<.0001) functioning on the SF-12, though after adjustment, only the difference in SF-12 physical functioning remained significant (p < .0001), with the postmenopausal group showing significantly lower physical functioning than both the premenopausal and perimenopausal groups (post-hoc comparions p < .0010 for both pairwise comparisons).

Table 2
Depression Characteristics by Menopausal Status

Profile of Depressive Symptoms

Table 3 shows individual depressive symptoms measured by the IDS-C30 compared on the basis of menopausal status. After adjustment for baseline differences, only early morning insomnia (OR Peri vs. Pre=1.79 (1.34, 2.36), OR Post vs. Pre=1.36 (1.02, 1.82), p = .0003), irritability (OR Peri vs. Pre=0.55 (0.38, 0.79), OR Post vs. Pre=0.43 (0.38, 0.79), p < .0001), decreased appetite (OR Peri vs. Pre=0.77 (0.59, 1.02), OR Post vs. Pre=0.64 (0.48, 0.85), p = .0081), suicidal ideation (OR Peri vs. Pre=1.16 (0.88, 1.54), OR Post vs. Pre=1.54 (1.16, 2.06), p = .0074), sympathetic arousal (OR Peri vs. Pre=1.39 (1.02, 1.90), OR Post vs. Pre=1.59 (1.14, 2.22), p = .0144), and gastrointestinal symptoms (OR Peri vs. Pre=1.31 (0.99, 1.73), OR Post vs. Pre=1.47 (1.10, 1.96), p = .0244) showed significant differences between groups. Post-hoc tests were performed for these symptoms to determine the significant differences between individual groups. Perimenopausal women were less likely to have irritability and were more likely to have early morning insomnia than premenopausal women. Postmenopausal women were more likely to have suicidal ideation, sympathetic arousal and gastrointestinal symptoms than premenopausal women, and less likely to have a decreased appetite and have irritability. Perimenopausal women were less likely to have suicidal ideation than postmenopausal women.

Table 3
Profile of Depressive Symptoms (IDS-C30) by Menopausal Status

Psychiatric Comorbidity

Table 4 provides rates of psychiatric comorbidity as a function of menopausal status. Premenopausal women were more likely to have a comorbid diagnosis of obsessive compulsive disorder (Pre: 17%, Peri: 12%, Post: 12%, p = .0116), social phobia (Pre: 38%, Peri: 27%, Post: 24%, p < .0001), drug abuse (Pre: 8%, Peri: 5%, Post: 3%, p = .0020), bulimia (Pre: 19%, Peri: 13%, Post: 13%, p = .0012), and generalized anxiety (Pre: 28%, Peri: 24%, Post: 22%, p = .0335) than the other groups. After adjustment, none of these differences in psychiatric comorbidity remained significant.

Table 4
Psychiatric Comorbidities (PDSQ) by Menopausal Status

Comparison of Postmenopausal Women Taking Versus Not Taking Hormone Therapy

Baseline sociodemographic and clinical characteristics of postmenopausal women by hormone therapy status are presented in Table 5. Women taking hormone therapy were significantly less likely to be Hispanic (Non-hormone: 20%, Hormone: 10%, p = .0031); more likely to be Caucasian (Non-hormone: White: 71%, Black 23%, Other 6%; Hormone: White 83%, Black 15%, Other 2%, p = .0031), married (Non-hormone: 35%, Hormone: 47%, p = .0066) and have private insurance (Non-hormone: 48%, Hormone: 61%, p = .0110), and had more years of education (Non-hormone: 12.3 (3.9), Hormone: 13.2 (3.4), p = .0025). Women taking hormone therapy were also more likely to have recurrent depression (Non-hormone: 69%, Hormone: 83%, p = .0006) and had, on average (SD), greater medical comorbidity on the CIRS (Non-hormone: 3.9 (2.4), Hormone: 4.5 (2.4), p = .0016).

Table 5
Baseline Characteristics in Postmenopausal Women by Hormone Therapy Status

We found no significant differences between the two groups with regard to the severity of depression HRSD17 (Non-hormone: 20.4 (6.7), Hormone: 20.0 (6.9), p=.5230) or the presence of atypical(Non-hormone: 17%, ormone: 14%, p=.3998) ; however, after adjustment for baseline sociodemographic and clinical differences, those taking hormone therapy were less likely to have melancholic features (OR=0.53 (.30, .93), p = .0289). Women taking hormone therapy had better physical functioning on the SF-12 (Non-hormone: 43.4 (11.9), Hormone: 45.7 (12.2), p=.0379), which remained significant, (β=−2.72 (−4.72, −0.73), p = .007) after adjustment for baseline sociodemographic and clinical differences (Table 6). Symptom profiles were similar between the two groups, except that even after adjustment for baseline sociodemographic and clinical differences, women taking hormone therapy were significantly more likely to endorse lack of involvement in activities (OR=2.02 (1.09, 3.75), p = .0266) and less likely to endorse sympathetic arousal (OR=0.62 (0.40, 0.97), p = .0359) (Table 7). With regard to psychiatric comorbidities on the PDSQ (Table 8), women taking hormone therapy were significantly less likely to report agoraphobia (Non-hormone: 14%, Hormone: 8%, p=.0400), although this difference was no longer significant after adjustment.

Table 6
Depression Characteristics in Postmenopausal Women by Hormone Therapy Status
Table 7
Profile of Depressive Symptoms in Postmenopausal Women by Hormone Therapy Status
Table 8
Psychiatric Co-Morbidities (PDSQ) in Postmenopausal Women by Hormone Therapy Status

DISCUSSION

To the best of our knowledge, this is the first study to examine the influence of menopausal status on the presentation of MDD in women, and the first to examine the effect of hormone therapy on the characteristics of major depression in postmenopausal women.

Our finding that postmenopausal women have more general medical comorbidity, an older age of onset, and less likelihood of family history of depression or past suicide attempt suggests that their depression may be related more to general medical comorbidity, hormonal factors, and/or aging than to a lifelong depressive disorder. After adjustment for baseline differences, we found several differences in symptom profiles among pre-, peri- and postmenopausal women. Our finding of more irritability in premenopausal women may reflect the influence of the menstrual cycle on the presentation of depression, since many women experience premenstrual worsening of depression or other premenstrual mood changes, of which irritability is the most common.48 It was surprising that postmenopausal women reported more suicidal ideation, particularly given the similarity of their severity of illness to the other groups and their less frequent history of suicide attempt. One could speculate that this increased suicidal ideation is related to their greater likelihood of being widowed or divorced, which may reflect a lack of social support, and their lower level of resources given their lower income and less private insurance. To examine whether marital status explained the finding, we compared mean score of the suicidal ideation item from the QIDS-SR16 across marital status groups and found no statistically significant difference in the scores. Our finding of a greater likelihood of sympathetic arousal, gastrointestinal symptoms and lower physical functioning in postmenopausal women, characteristics which were present even after adjustment for differences in general medical comorbidity, may be a reflection of age, as these symptoms were also noted to increase with age in a study by Husain et al.,49 who conducted a recent analysis of age-related characteristics of depression that also used the STAR*D population for its study sample . However, an independent effect of hormones is suggested by the fact that postmenopausal women in the study taking hormone therapy had a lower rate of sympathetic arousal and higher physical functioning; this is also consistent with findings in premenopausal women taking versus not taking hormonal contraceptives in another report from the STAR*D study.24

Previous reports suggest that women commonly present with atypical depressive features, such as hypersomnia and hyperphagia.4,5,7,50 Interestingly, we found no difference in the presence of atypical or melancholic features of depression by menopausal status, with about 20% of women in each group showing each of these subtypes. While hypersomnia was more common in premenopausal women than in the other two groups, the difference was no longer significant after adjustment. We did find that early morning insomnia was less common and decreased appetite was more common in premenopausal women; however, it is important to note that in all three of the menopausal status groups, midnocturnal awakening was the most common sleep disturbance and decreased appetite was more common than increased appetite. It is also notable that anxious depression was the most common subtype among all three groups and was seen most frequently in postmenopausal women, although the difference by menopausal status was no longer significant after adjustment.

In addition to differences in the presentation of depression by menopausal status, we also found that depression in postmenopausal women may be influenced by whether or not concomitant hormone therapy is being taken. The women in our study who were taking hormone therapy were more likely to be Caucasian, non-Hispanic, or married, with more years of education and private insurance. The higher educational level in women taking hormone therapy is consistent with the literature50 prior to the publication of the Women's Health Initiative results,51 which is when our study was initiated. Women taking hormone therapy were also more likely to have a recurrent course of depression and greater general medical comorbidity. The greater general medical comorbidity in women taking hormone therapy likely results in increased contact with health care providers and therefore increased opportunities for hormone therapy to be prescribed.

Comparing symptom profiles after adjustment for baseline differences, women on hormone therapy reported better physical functioning, fewer melancholic features, less sympathetic arousal, and more lack of involvement in activities compared to women not on hormone therapy. The better physical functioning, less melancholia, and less sympathetic arousal (i.e., less anxiety) are consistent with the beneficial effects on sleep, energy, mood, and quality of life that have been described with hormone therapy.52 However, the similar overall severity of depression in those taking and not taking hormone therapy is consistent with literature showing that estrogen is not a treatment for major depression in postmenopausal women,53 although it also suggests that hormone therapy does not worsen depressive symptoms.

There are several limitations to this study. The sample was restricted to outpatients with nonpsychotic MDD and may not be generalizable to all depressed women. It was not a random sample of depressed patients as seen in epidemiologic studies; however, we did use broad inclusion criteria, recruited patients from primary and psychiatric care sites across the United States, and had appropriate minority representation. Hence, our sample was probably representative of depressed patients seeking care in outpatient settings. Another limitation was the definition of menopausal status used, which was based on a combination of age and a question about menopausal status and hysterectomy status. More detailed questions about irregular or skipped menstrual cycles and timing of cessation of cycles would have enabled more exact classification of women as pre-, peri, or postmenopausal. In addition, we do not know the timing of the onset of depression in postmenopausal women in relation to their beginning or stopping hormone therapy, information that may have further clarified the effect of hormone therapy on depressive symptom presentation. It is also true that—at least to some extent—age and menopausal status covary and some of the differences identified may have more to do with age differences than reproductive hormonal status. Much of our data rely on self-report and patient recall, which may be unreliable. Finally, the self-report PDSQ was used to diagnose comorbid Axis I psychiatric disorders though it is a screening tool.

In conclusion, the depressive episode presentation in women may be influenced by menopausal status as well as postmenopausal use of hormone therapy. The differences reported should be considered in the clinical evaluation and management of female patients with depression. Future analyses will examine the impact of menopausal status and hormone therapy on antidepressant treatment response.

Acknowledgments

SOURCE OF FUNDING

This project has been funded with federal funds from the National Institute of Mental Health, National Institutes of Health, under Contract N01MH90003 to UT Southwestern Medical Center at Dallas (P.I.: A.J. Rush). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors appreciate the editorial support of Jon Kilner, MS, MA (Pittsburgh, PA).

CONFLICTS OF INTEREST

Susan G Kornstein, M.D.

Grants/Research Support: National Institute of Mental Health; Bristol-Myers Squibb; Lilly; Forest Laboratories; Wyeth; Novartis; Boehringer-Ingelheim; Pfizer; Takeda.

Advisory Board or Received Honoraria: Wyeth; Pfizer; Lilly; Bristol-Myers Squibb; Forest Laboratories; Takeda; Endo.

Book Royalties: Guilford Press.

Elizabeth A. Young, MD*

Research Support: National Institute of Mental Health and National Institute of Child Health and Human Development

Annie T. Harvey, Ph.D.

Research Support: Pfizer Inc. Except for income received from her primary employer, no other financial support or compensation was received from any individual or corporate entity for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.

Stephen R. Wisniewski, Ph.D.

Research Support: National Institute of Mental Health

Advisory/Consulting: Cyberonics, Inc.

Speaking: None

Equity Holdings (exclude mutual funds/blinded trusts): None

Royalty/patent, other income: None

Michael E. Thase, M.D.

Advisory/Consulting:/Speakers Honoraria: AstraZeneca, Bristol-Myers Squibb, Cephalon, Cyberonics, Inc., Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceutica, MedAvante, Inc., Neuronetics, Inc., Novartis, Organon, Inc., Sanofi-Aventis, Sepracor, Inc., Shire US, Inc., and Wyeth Pharmaceuticals

Equity Holdings: MedAvante, Inc.

royalty/Patent or Other Income: American Psychiatric Publishing, Inc., Guilford Publications, and Herald House.

Dr. Thase did not accept research funding from pharmaceutical studies during the STAR*D study, but currently has grants from Eli Lilly and Company and Sepracor, Inc.

Madhukar H. Trivedi, M.D.

Research support: Bristol-Myers Squibb Company; Cephalon, Inc.; Corcept Therapeutics, Inc.; Eli Lilly & Company; GlaxoSmithKline; Janssen Pharmaceutica; National Institute of Mental Health; National Alliance for Research in Schizophrenia and Depression; Pfizer Inc.; Predix Pharmaceuticals; Wyeth-Ayerst Laboratories

Advisory/Consulting: Abbott Laboratories, Inc.; Akzo (Organon Pharmaceuticals Inc.); Bayer; Bristol-Myers Squibb Company; Cyberonics, Inc.; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica Products, LP; Johnson & Johnson PRD; Eli Lilly & Company; Meade Johnson; Parke-Davis Pharmaceuticals, Inc.; Pfizer, Inc.; Pharmacia & Upjohn; Sepracor; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories

Speaking: Akzo (Organon Pharmaceuticals Inc.); Bristol-Myers Squibb Company; Cyberonics, Inc.; Forest Pharmaceuticals; Janssen Pharmaceutica Products, LP; Eli Lilly & Company; Pharmacia & Upjohn; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories

Equity Holdings (exclude mutual funds/blinded trusts): None

Royalty/patent, other income: None

Andrew A. Nierenberg, M.D.

Research support: Bristol-Myers Squibb Company; Cederroth; Cyberonics, Inc.; Forest Pharmaceuticals Inc.; GlaxoSmithKline; Janssen Pharmaceutica; Lichtwer Pharma; Eli Lilly & Company; PamLabs; Pfizer Inc.; National Institute of Mental Health; National Alliance for Research in Schizophrenia and Depression, Stanley Foundation; Wyeth-Ayerst Laboratories

Advisory/Consulting: Astra-Zeneca; Basilea Pharmaceutica; Brain Cells, Inc., Bristol-Myers Squibb Company; Dainippon Sumitomo; Eli Lilly & Company; EpiQ; Genaissance; GlaxoSmithKline; Jazz Pharmaceuticals; Innapharma; Merck; Neuronetics; Novartis; Pfizer, Inc.; PGx Health; Sepracor; Shire; Targacept; Takeda

Speaking: Eli Lilly & Company; GlaxoSmithKline; Organon, Inc.; Wyeth-Ayerst Laboratories; Massachusetts General Psychiatry Academy (MGHPA talks are supported through Independent Medical Education (IME) grants from the following pharmaceutical companies in 2008: Astra Zeneca, Eli Lilly, and Janssen Pharmaceuticals.) No other speaker bureaus since 2003.

Equity Holdings (exclude mutual funds/blinded trusts): Appliance Computing, Inc.

Royalty/patent, other income: None

A. John Rush, M.D.

Research support: National Institute of Mental Health

Advisory/Consulting: Advanced Neuronetic Systems, Inc.; AstraZeneca; Best Practice Project Management, Inc.; Bristol-Myers Squibb Company; Cyberonics, Inc.; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Healthcare Technology Systems, Inc.; Jazz Pharmaceuticals; Eli Lilly & Company; Magellan Health Services; Merck & Co., Inc.; Neuronetics; Ono Pharmaceutical; Organon USA Inc.; Personality Disorder Research Corp.; Pfizer Inc.; and Wyeth-Ayerst Laboratories Inc.

Speaking: Cyberonics, Inc.; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Eli Lilly & Company; and Merck & Co., Inc.

Equity Holdings (exclude mutual funds/blinded trusts): Pfizer Inc.

Royalty/patent, other income: Guilford Publications; Healthcare Technology Systems, Inc.

Jennifer Barkin, Ph.D. has no disclosures to report.

Footnotes

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Contributor Information

Susan G. Kornstein, Department of Psychiatry and Institute for Women's Health, Virginia Commonwealth University.

Elizabeth A. Young, Department of Psychiatry and Molecular and Behavioral Neurosciences Institute, University of Michigan.

Annie T. Harvey, Via Christi Research, Via Christi Regional Medical Center, 1100 N. St. Francis, Suite 300, Wichita, Kansas 67214.

Stephen R. Wisniewski, Epidemiology Data Center, GSPH, University of Pittsburgh.

Jennifer L. Barkin, University of Pittsburgh Medical Center, Western Psychiatric Institute and Clinic.

Michael E. Thase, Department of Psychiatry, University of Pennsylvania.

Madhukar H. Trivedi, Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas.

Andrew A. Nierenberg, Department of Psychiatry, Massachusetts General Hospital.

A. John Rush, Departments of Clinical Sciences and Psychiatry, University of Texas Southwestern Medical Center at Dallas, and Duke-National University of Singapore, Singapore.

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