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      Adrenal activity and metabolic risk during randomized escitalopram or placebo treatment in PCOS

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          Abstract

          Background/aims

          Polycystic ovary syndrome (PCOS) is associated with insulin resistance, adrenal hyperactivity and decreased mental health. We aimed to investigate the changes in adrenal activity, metabolic status and mental health in PCOS during treatment with escitalopram or placebo.

          Methods

          Forty-two overweight premenopausal women with PCOS and no clinical depression were randomized to 12-week SSRI (20 mg escitalopram/day, n = 21) or placebo ( n = 21). Patients underwent clinical examination, fasting blood samples, adrenocorticotroph hormone (ACTH) test, 3-h oral glucose tolerance test (OGTT) and filled in questionnaires regarding mental health and health-related quality of life (HRQoL): WHO Well-Being Index (WHO-5), Major Depression Inventory (MDI), Short Form 36 (SF-36) and PCOS questionnaire.

          Results

          Included women were aged 31 (6) years (mean ( s.d.)) and had body mass index (BMI) 35.8 (6.5) kg/m 2 and waist 102 (12) cm. Escitalopram was associated with increased waist (median (quartiles) change 1 (0; 3) cm), P = 0.005 vs change during placebo and increased cortisol levels (cortisol 0, cortisol 60, peak cortisol and area under the curve for cortisol during ACTH test), all P< 0.05 vs changes during placebo. Escitalopram had no significant effect on measures of insulin sensitivity, insulin secretion, fasting lipids, mental health or HRQoL.

          Conclusion

          Waist circumference and cortisol levels increased during treatment with escitalopram in women with PCOS and no clinical depression, whereas metabolic risk markers, mental health and HRQol were unchanged.

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          Most cited references38

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          Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study.

          There is a central belief that depression is associated with hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in higher cortisol levels. However, results are inconsistent. To examine whether there is an association between depression and various cortisol indicators in a large cohort study. Data are from 1588 participants of the Netherlands Study of Depression and Anxiety who were recruited from the community, general practice care, and specialized mental health care. Three groups were compared: 308 control subjects without psychiatric disorders, 579 persons with remitted (no current) major depressive disorder (MDD), and 701 persons with a current MDD diagnosis, as assessed using the DSM-IV Composite International Diagnostic Interview. Cortisol levels were measured in 7 saliva samples to determine the 1-hour cortisol awakening response, evening cortisol levels, and cortisol suppression after a 0.5-mg dexamethasone suppression test. Both the remitted and current MDD groups showed a significantly higher cortisol awakening response compared with control subjects (effect size [Cohen d] range, 0.15-0.25). Evening cortisol levels were higher among the current MDD group at 10 pm but not at 11 pm. The postdexamethasone cortisol level did not differ between the MDD groups. Most depression characteristics (severity, chronicity, symptom profile, prior childhood trauma) were not associated with hypothalamic-pituitary-adrenal axis activity except for comorbid anxiety, which tended to be associated with a higher cortisol awakening response. The use of psychoactive medication was generally associated with lower cortisol levels and less cortisol suppression after dexamethasone ingestion. This large cohort study shows significant, although modest, associations between MDD and specific hypothalamic-pituitary-adrenal axis indicators. Because a higher cortisol awakening response was observed among both subjects with current MDD and subjects with remitted MDD, this may be indicative of an increased biological vulnerability for depression.
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            The polycystic ovary syndrome: a position statement from the European Society of Endocrinology.

            Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.
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              The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                March 2018
                22 February 2018
                : 7
                : 3
                : 479-489
                Affiliations
                [1 ]Department of Endocrinology and Metabolism Odense University Hospital, Odense, Denmark
                [2 ]Department of Gynecology and Obstetrics Odense University Hospital, Odense, Denmark
                [3 ]Department of Psychiatry Odense University Hospital, Odense, Denmark
                Author notes
                Correspondence should be addressed to D Glintborg: dorte.glintborg@ 123456rsyd.dk
                Article
                EC180077
                10.1530/EC-18-0077
                5861369
                29472241
                8455d877-1c59-400b-a52b-490ee90ec158
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 16 February 2018
                : 22 February 2018
                Categories
                Research

                pcos,cortisol,mental health,quality of life,pcosq,escitalopram,ssri
                pcos, cortisol, mental health, quality of life, pcosq, escitalopram, ssri

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