Depression during the menopause transition: impact on quality of life, social adjustment, and disability.

The impact of depression on quality of life (QOL) and social support has neither been well characterized in clinical samples of women with perimenopausal depression (PMD) nor have the relative contributions of depression and other menopausal symptoms (e.g., hot flushes) to declining QOL been clarified. In this study, we compared QOL measures, social support, and functional disability in PMD and non-depressed perimenopausal women. We evaluated women aged 40-60 years who presented with menstrual cycle irregularity, elevated plasma FSH levels, and met criteria for perimenopause. A structured clinical interview was administered to determine the presence or absence of major and minor depression. Outcome measures included the Quality of Life Enjoyment Scale Questionnaire, the Sheehan Disability Scale, the Global Assessment of Functioning, the Social Adjustment Scale, and the Duke Social Support Index. Kruskal-Wallis tests and ANOVAs were used to compare outcome measures. Ninety women with PMD and 51 control women participated in this study. Women with PMD reported significantly decreased QOL, social support, and adjustment and increased disability compared with non-depressed perimenopausal women. Neither perimenopausal reproductive status alone nor the presence of hot flushes had a significant negative impact on QOL measures. PMD is accompanied by significant reductions in QOL, social support, and disability similar to depression in women at other stages of life. PMD may also contribute to decreased QOL in community- or clinic-based samples of perimenopausal women. It remains unclear whether the clinical characteristics we identified reflect pre-existing risk factors for depression during the perimenopause or the effects of a current depression. Future clinical and treatment studies in perimenopausal women should distinguish depressed women when outcome measures include QOL.

History of postpartum depression in a clinic-based sample of women with premenstrual dysphoric disorder.

OBJECTIVE: Overlapping comorbidities between premenstrual dysphoric disorder (PMDD) and postpartum depression (PPD) suggest that these disorders represent a continuum of vulnerability with shared pathophysiology. We report the past histories of PPD (and other Axis I psychiatric illnesses) in a clinic-based sample of women meeting criteria for PMDD. METHODS: 215 women, ages 19 to 51 years, who attended the National Institute of Mental Health Mood Disorders Clinic between 1988 and 2013 seeking treatment for PMDD and in whom we confirmed the diagnosis of PMDD (DSM-IV), were identified. All were administered the Structured Clinical Interview for DSM-III-R or -IV. The frequency of PPD (major or minor) was established in the subgroup of women (n = 137) who had delivered at least 1 child. RESULTS: Ninety-three women (43.3%) had a past history of a mood disorder (ie, either major [n = 67; 31.2%] or minor [n = 10; 4.7%] depression or PPD [n = 16; 7.4%; 11.7% of parous women]). Nine of the 16 women with PMDD and a past PPD had either a past major depressive episode (MDE) or subsyndromal anxiety disorder. Thirty-three women (15.3%) had a past history of an Axis I anxiety disorder. A total of 40 women (18.6%) met criteria for past alcohol or drug abuse, 3 (1.4%) met criteria for bulimia nervosa, and 2 (0.9%) met criteria for anorexia nervosa. CONCLUSIONS: Our data demonstrate that PMDD and PPD do not frequently co-occur. These data do not suggest that PMDD and PPD share similar pathophysiology beyond being ovarian-steroid-triggered mood disorders. The high comorbidity of past MDE could contribute to the increased risk both for future MDE and for PPD in some women with PMDD.

Effects of physiologic testosterone therapy on quality of life, self-esteem, and mood in women with primary ovarian insufficiency.

OBJECTIVE: Women with primary ovarian insufficiency (POI) display low androgen levels, which could contribute to mood and behavioral symptoms observed in this condition. We examined the effects of physiologic testosterone therapy added to standard estrogen/progestin therapy on quality of life, self-esteem, and mood in women with POI. METHODS: One hundred twenty-eight women with 46,XX spontaneous POI participated in a 12-month randomized, placebo-controlled, parallel-design investigation of the efficacy of testosterone augmentation of estrogen/progestin therapy. Quality of life, self-esteem, and mood symptoms were evaluated with standardized rating scales and a structured clinical interview. Differences in outcome measures between the testosterone and placebo treatments were analyzed by Wilcoxon rank sum tests. RESULTS: No differences in baseline characteristics, including serum hormone levels (P > 0.05), were found. Baseline mean (SD) Center for Epidemiologic Studies Depression Scale scores were 10.7 (8.6) and 9.2 (7.8) for testosterone and placebo, respectively (P = 0.35). After 12 months of treatment, measures of quality of life, self-esteem, and mood symptoms did not differ between treatment groups. Serum testosterone levels achieved physiologic levels in the testosterone group and were significantly higher compared with placebo (P < 0.001). Baseline testosterone levels were not associated with either adverse or beneficial clinical effects. CONCLUSIONS: A 150-µg testosterone patch achieves physiologic hormone levels in women with POI. Our findings suggest that augmentation of standard estrogen/progestin therapy with physiologic testosterone therapy in young women with POI neither aggravates nor improves baseline reports of quality of life or self-esteem and had minimal effects on mood. Other mechanisms might play a role in the altered mood accompanying this disorder.

Depression in women with spontaneous 46, XX primary ovarian insufficiency.

CONTEXT: A high prevalence of depressive symptoms is observed in women with primary ovarian insufficiency (POI) compared with women in whom the menopause is normally timed. Indeed, studies suggest that depression and/or its pharmacological treatment contribute to the onset of POI. OBJECTIVES: We characterize the prevalence of psychiatric disorders and the timing of onset of clinically significant depression relative to both the diagnosis of POI and the onset of menstrual irregularity in women with POI. DESIGN AND SETTING: We conducted a cross-sectional clinic-based study at the National Institutes of Health Clinical Research Center. PATIENTS: A total of 174 women with spontaneous 46, XX POI and 100 women with Turner syndrome participated in the study. MAIN OUTCOME MEASURES: The structured clinical interview for DSM-IV was performed. RESULTS: Lifetime histories of depression in POI exceeded rates of depression reported in women with Turner syndrome and community-based samples of women (P < 0.001). The onset of depression frequently preceded the diagnosis of POI but occurred after the onset of menstrual irregularity. Analyses standardizing the periods of risk for depression showed that similar numbers of depressions occurred before and after these events. CONCLUSIONS: POI is associated with an increased lifetime risk for major depression. Attention to the presence of depression in POI should become an important part of the care for these women. The onset of depression frequently occurs after signs of altered ovarian function but before the diagnosis of POI. Thus, in some women the association between POI and depression suggests an overlapping pathophysiology rather than a causal relationship.

Pharmacologically induced hypogonadism and sexual function in healthy young women and men.

Studies fail to find uniform effects of age-related or induced hypogonadism on human sexual function. We examined the effects of induced hypogonadism on sexual function in healthy men and women and attempted to identify predictors of the sexual response to induced hypogonadism or hormone addback. The study design used was a double-blind, controlled, crossover (self-as-own control). The study setting was an ambulatory care clinic in a research hospital, and the participants were 20 men (average+/-SD age=28.5+/-6.2 years) and 20 women (average+/-SD age=33.5+/-8.7 years), all healthy and with no history of psychiatric illness. A multidimensional scale assessing several domains of sexual function was the main outcome measure. Participants of the study received depot leuprolide acetate (Lupron) every 4 weeks for 3 months (men) or 5 months (women). After the first month of Lupron alone, men received (in addition to Lupron) testosterone enanthate (200 mg intramuscularly) or placebo every 2 weeks for 1 month each. Women received Lupron alone for 2 months, and then, in addition to Lupron, they received estradiol and progesterone for 5 weeks each. The results of the study: in women, hypogonadism resulted in a significant decrease in global measures of sexual functioning, principally reflecting a significant decrease in the reported quality of orgasm. In men, hypogonadism resulted in significant reductions in all measured domains of sexual function. Testosterone restored sexual functioning scores in men to those seen at baseline, whereas neither estradiol nor progesterone significantly improved the reduced sexual functioning associated with hypogonadism in women. Induced hypogonadism decreased sexual function in a similar number of men and women. No predictors of response were identified except for levels of sexual function at baseline. In conclusion, our data do not support a simple deficiency model for the role of gonadal steroids in human sexual function; moreover, while variable, the role of testosterone in sexual function in men is more apparent than that of estradiol or progesterone in women.

A cross-sectional evaluation of perimenopausal depression.

OBJECTIVE: Overall, the clinical spectrum of depression during the perimenopause is not well characterized. This cross-sectional study examined the following: (1) clinical characteristics of women who presented to the National Institute of Mental Health midlife mood disorders clinic (between March 1990 and January 2004) with peri-menopausal major and minor depressions and (2) the impact on these characteristics of either a prior episode of depression or the presence of hot flushes. METHOD: Historical variables, reproductive status, symptom ratings, and plasma hormone measures were examined in 116 women between the ages of 40 and 55 years who met research criteria for perimenopause-related depression (a current episode of major or minor depression according to the Structured Clinical Interview for DSM-IV or Primary Care Evaluation of Mental Disorders supplemented with a past history form). RESULTS: Clinical characteristics did not differ in those women with first-onset (39%) versus recurrent depressions or in those with (57%) and without hot flushes. Depressive episodes clustered in the later stages of the menopause transition and the first year postmenopause. Seven women (6%) reported a past postpartum major depression, and 55% of women reported a history of premenstrual dysphoria (PMD). CONCLUSIONS: We found no evidence that either hot flushes or a previous episode of depression conveys a distinct clinical profile in these women. The clustering of onsets of depression suggests the hormone events that characterize the late menopause transition may be relevant to the onset of this form of depression. Finally, although we observed a high rate of PMD, neither postpartum depression nor PMD are consistent accompaniments of perimenopausal depression.

Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression.

CONTEXT: Alternative and over-the-counter medicines have become increasingly popular choices for many patients who prefer not to take traditional antidepressants. The adrenal androgen and neurosteroid dehydroepiandrosterone (DHEA) is available as over-the-counter hormonal therapy and previously has been reported to have antidepressant-like effects. OBJECTIVE: To evaluate the efficacy of DHEA as a monotherapy treatment for midlife-onset depression. DESIGN: A double-blind, randomized, placebo-controlled, crossover treatment study was performed from January 4, 1996, through August 31, 2002. Settings The National Institute of Mental Health Midlife Outpatient Clinic in the National Institutes of Health Clinical Center, Bethesda, Md. Patients Men (n = 23) and women (n = 23) aged 45 to 65 years with midlife-onset major or minor depression participated in this study. None of the subjects received concurrent antidepressant medications. Intervention Six weeks of DHEA therapy, 90 mg/d for 3 weeks and 450 mg/d for 3 weeks, and 6 weeks of placebo. MAIN OUTCOME MEASURES: The 17-Item Hamilton Depression Rating Scale and Center for Epidemiologic Studies Depression Scale. Additional measures included the Derogatis Interview for Sexual Functioning. Results were analyzed by means of repeated-measures analysis of variance and post hoc Bonferroni t tests. RESULTS: Six weeks of DHEA administration was associated with a significant improvement in the 17-Item Hamilton Depression Rating Scale and the Center for Epidemiologic Studies Depression Scale ratings compared with both baseline (P<.01) and 6 weeks of placebo treatment (P<.01). A 50% or greater reduction in baseline Hamilton Depression Rating Scale scores was observed in 23 subjects after DHEA and in 13 subjects after placebo treatments. Six weeks of DHEA treatment also was associated with significant improvements in Derogatis Interview for Sexual Functioning scores relative to baseline and placebo conditions. CONCLUSION: We find DHEA to be an effective treatment for midlife-onset major and minor depression.

A longitudinal evaluation of the relationship between reproductive status and mood in perimenopausal women.

OBJECTIVE: Mood and reproductive function were prospectively evaluated in asymptomatic premenopausal women to determine whether the onset of depression was temporally linked to the perimenopause. METHOD: Twenty-nine asymptomatic, regularly cycling women were monitored longitudinally for an average of 5 years until at least 6 months of amenorrhea occurred. Outcome measures included mood ratings and menstrual diaries completed daily, the Structured Clinical Interview for DSM-IV, and plasma levels of follicle-stimulating hormone obtained at 3-6-month intervals. The number of episodes of depression and their timing relative to the final menstrual period were determined. Differences in outcome measures between women who did and did not become depressed during the perimenopause were determined by Student's t test, chi-square tests, and Fisher's exact test. RESULTS: The authors observed 11 episodes of new-onset depression in nine of the 29 women. In the 24 months surrounding the last menstrual period nine episodes of depression were observed. Six of the nine women who became depressed during the study had no prior depressive episodes. For the 24 months surrounding the final menses, the risk for onset of depression was 14 times as high as for a 31-year premenopausal period of time. Women who developed depression during the perimenopause were not distinguished from those who remained asymptomatic on the basis of symptom profile, duration of the perimenopause, endocrine measures, or past historical variables. CONCLUSIONS: These preliminary data suggest that events related to the late perimenopause may be associated with an increased susceptibility to develop depression in some women.

The effects of pharmacologically induced hypogonadism on mood in healthy men.

BACKGROUND: The effects of declining androgen secretion on mood regulation and the potential psychotropic efficacy of androgen replacement in men are largely undetermined. OBJECTIVE: To examine the effects on mood of the acute suppression of testosterone secretion. DESIGN: A double-blind, placebo-controlled, crossover (self-as-own-control) study. SETTING: An ambulatory care clinic in a research hospital. PARTICIPANTS: Thirty-one healthy adult men with no history of psychiatric illness or substance or anabolic steroid abuse. INTERVENTIONS: Men received depot leuprolide acetate (Lupron, 7.5 mg intramuscularly) every 4 weeks for 3 months. After the first month of Lupron alone, all men received (in addition to Lupron) testosterone enanthate (200 mg intramuscular) or placebo (sesame oil as color-matched vehicle) every 2 weeks for 1 month each in a crossover design. The order of administration of testosterone and placebo was randomly assigned and counterbalanced. MAIN OUTCOME MEASURES: Mood and behavior rating scores (self-report and rater administered). RESULTS: With the exceptions of hot flushes, libido, and the feeling of being emotionally charged, none of the symptoms measured showed a significant difference across eugonadal, Lupron plus placebo, and Lupron plus testosterone conditions. Despite the absence of a uniform effect of Lupron plus placebo on mood, 3 men experienced clinically relevant mood symptoms during this induced hypogonadal condition. High baseline levels of sexual functioning predicted the greatest decline in sexual function during Lupron plus placebo. CONCLUSIONS: These data, the first to describe the effects on mood of induced hypogonadism in healthy young men, suggest that short-term hypogonadism is sufficient to precipitate depressive symptoms in only a small minority of younger men. The predictors of this susceptibility remain to be determined.

Current and lifetime psychiatric illness in women with Turner syndrome.

Abnormalities in quality of life and cognitive measures have been observed in women with Turner syndrome (TS), and a relationship between these phenomena and chromosomal constitution has been suggested. In contrast, few studies have systematically evaluated the presence of mood and behavioral syndromes in these women. In this study, 100 TS women were administered the Structured Clinical Interview for DSM IV after a two-week period during which their hormone replacement had been discontinued. The majority of women who met criteria for a psychiatric condition had a mood or anxiety disorder. Overall, 52 (52%) of the TS women met criteria for a current or a past depressive or anxiety disorder. Eighteen of the women with TS met criteria for a current Axis I psychiatric disorder [Depression--major (n = 5), minor (n = 5), dysthymia (n = 1); Anxiety (n = 9)]. Forty-six of the women with TS met criteria for a past Axis I psychiatric illness [Depression: unipolar (n = 41), bipolar (n = 3); Anxiety (n= 7); eating disorder (n =6); substance dependence (n = 3)]. Five women with TS met criteria for an Axis II personality disorder. Women with TS reported a higher rate of lifetime depression compared with rates observed in community-based studies but similar to those obtained from gynecologic clinic samples.