Nazli Haq

Basal plasma hormone levels in depressed perimenopausal women

BACKGROUND An association between abnormal changes in reproductive endocrine function during the perimenopause and the onset of depression in some women has been suggested but remains controversial. METHODS We examined basal plasma hormone levels in two samples of women with well characterized, first onset depression (major or minor) during the perimenopause and matched comparison groups of asymptomatic women. Results were compared by analysis of variance. RESULTS No significant diagnosis-related differences were observed in plasma hormone measures of the following: follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), estrone (E1), total (T) or free testosterone (FT), or the E2/LH ratio. We did identify significantly lower morning plasma dehydroepiandrosterone (DHEA) and its sulphated metabolite DHEA-S (but not cortisol) levels in the depressed women compared to the non-depressed comparison group. Women with hot flushes (regardless of the presence of depression) were significantly older than women without flushes, had significantly higher plasma levels of FT, LH and FSH, and had significantly lower E2/LH ratios. CONCLUSIONS Women with first onset depression during the perimenopause are not distinguished from controls on the basis of basal hormone measures of ovarian estrogens, testosterone, or gonadotropins. However, perimenopause-related changes in E2 may interact with low levels of DHEA in some women to increase their vulnerability to develop depression. In contrast to perimenopause-related vasomotor symptoms, depression during the perimenopause is not associated with a simple hormone deficiency state. The relatively low levels of E2 and E1 in the depressed women may have met statistical significance in a much larger and homogenous sample.

Stressful life events, personal losses, and perimenopause-related depression

SummaryWe compared the number and quality of life events reported by depressed perimenopausal women and a non-depressed comparison group. Additionally, we examined the effects of the presence of hot flushes on life event reports. All women were 44–55 years old, had irregular menses and elevated plasma gonadotropin levels. The Psychiatric Epidemiology Research Interview recorded both the frequency of occurrence and the desirability of life events experienced by the women during the six months prior to the interview. Depressed perimenopausal women (n=50) reported significantly more undesirable events [Student’s t-test (unpaired) with Bonferroni correction, t98=3.9, p=0.001] but not more exit events (e.g., divorce, last child leaving home or death in family) (t98=0.9, p=NS) compared to the non-depressed women (n=50). There were no effects of hot flushes on these diagnostic differences. The “empty nest” syndrome does not appear to be relevant in the development of perimenopausal depression. Nevertheless, independent of the presence of hot flushes, perimenopausal depressed women are more likely to report both negative life events and diminished self esteem.

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.

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.

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.

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

ObjectiveWomen 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. MethodsOne 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. ResultsNo 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. ConclusionsA 150-&mgr;g 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.

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.

Pharmacologically induced hypogonadism and sexual function in healthy young women and men (Neuropsychopharmacology (2008) (5) doi:10.1038/sj.npp.2008.24)

In this article, page 5, right column, fifth paragraph, line 2, first sentence following run-in head (‘Comparisons between those with high and low baseline DISF scores.’) should be ‘Women with low and high total DISF scores at baseline had significantly different responses to induced hypogonadism (Figure 2).’ Neuropsychopharmacology (2009) 34, 816 & 2009 Nature Publishing Group All rights reserved 0893-133X/09

Dehydroepiandrosterone Monotherapy in Midlife-Onset Major and Minor Depression

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