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      Hormonal contraception increases the risk of psychotropic drug use in adolescent girls but not in adults: A pharmacoepidemiological study on 800 000 Swedish women

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          Abstract

          The burden of depression and anxiety disorders is greater in women, and female sex hormones have been shown to affect mood. Psychological side effects of hormonal contraception (HC) are also a common complaint in the clinic, but few previous studies have investigated this subject. We therefore wanted to investigate whether use of HC was associated with adverse psychological health outcomes, and whether this association was modified by age. All women aged 12–30 years on 31 December 2010, residing in Sweden for at least four years and with no previous psychiatric morbidity (n = 815 662), were included. We followed the women from their first HC use (or 31 December 2010, if they were non-users) at baseline, until a prescription fill of psychotropic drugs or the end of the one-year follow-up. We performed age-stratified logistic regression models and estimated odds ratios (OR) to measure the association between different HC methods and psychotropic drug use, as well as the area under the receiver operating curve to estimate discriminatory accuracy of HC in relation to psychotropic drugs. Overall, we found an association between HC and psychotropic drugs (adjusted OR 1.34, 95% confidence interval [CI] 1.30–1.37). In the age-stratified analysis, the strongest association was found in adolescent girls (adjusted OR 3.46, 95% CI 3.04–4.94 for age 12 to 14 years), while it was non-existent for adult women. We conclude that hormonal contraception is associated with psychotropic drug use among adolescent girls, suggesting an adverse effect of HC on psychological health in this population.

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          Most cited references35

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          Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker.

          M. S. Pepe (2004)
          A marker strongly associated with outcome (or disease) is often assumed to be effective for classifying persons according to their current or future outcome. However, for this assumption to be true, the associated odds ratio must be of a magnitude rarely seen in epidemiologic studies. In this paper, an illustration of the relation between odds ratios and receiver operating characteristic curves shows, for example, that a marker with an odds ratio of as high as 3 is in fact a very poor classification tool. If a marker identifies 10% of controls as positive (false positives) and has an odds ratio of 3, then it will correctly identify only 25% of cases as positive (true positives). The authors illustrate that a single measure of association such as an odds ratio does not meaningfully describe a marker's ability to classify subjects. Appropriate statistical methods for assessing and reporting the classification power of a marker are described. In addition, the serious pitfalls of using more traditional methods based on parameters in logistic regression models are illustrated.
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            Association of Hormonal Contraception With Depression

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              The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey Replication.

              Only limited information exists about the epidemiology of DSM-IV panic attacks (PAs) and panic disorder (PD). To present nationally representative data about the epidemiology of PAs and PD with or without agoraphobia (AG) on the basis of the US National Comorbidity Survey Replication findings. Nationally representative face-to-face household survey conducted using the fully structured World Health Organization Composite International Diagnostic Interview. English-speaking respondents (N=9282) 18 years or older. Respondents who met DSM-IV lifetime criteria for PAs and PD with and without AG. Lifetime prevalence estimates are 22.7% for isolated panic without AG (PA only), 0.8% for PA with AG without PD (PA-AG), 3.7% for PD without AG (PD only), and 1.1% for PD with AG (PD-AG). Persistence, lifetime number of attacks, and number of years with attacks increase monotonically across these 4 subgroups. All 4 subgroups are significantly comorbid with other lifetime DSM-IV disorders, with the highest odds for PD-AG and the lowest for PA only. Scores on the Panic Disorder Severity Scale are also highest for PD-AG (86.3% moderate or severe) and lowest for PA only (6.7% moderate or severe). Agoraphobia is associated with substantial severity, impairment, and comorbidity. Lifetime treatment is high (from 96.1% for PD-AG to 61.1% for PA only), but 12-month treatment meeting published treatment guidelines is low (from 54.9% for PD-AG to 18.2% for PA only). Although the major societal burden of panic is caused by PD and PA-AG, isolated PAs also have high prevalence and meaningful role impairment.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Project administration
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 March 2018
                2018
                : 13
                : 3
                : e0194773
                Affiliations
                [001]Unit of Social Epidemiology, Department of Clinical Sciences, Lund University, Clinical Research Center, Malmö, Sweden
                Karolinska Institutet, SWEDEN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-3181-8609
                Article
                PONE-D-17-36799
                10.1371/journal.pone.0194773
                5864056
                29566064
                2c4c01a4-6d4e-4b6e-b4d7-804c56da765b
                © 2018 Zettermark et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 October 2017
                : 11 March 2018
                Page count
                Figures: 2, Tables: 2, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004359, Vetenskapsrådet;
                Award ID: 2013-2484
                Award Recipient :
                This work was supported by the Swedish Scientific Council (# 2013-2484, PI: Juan Merlo) and research funds from the Faculty of Medicine, Lund University, and Region Skåne County Council.
                Categories
                Research Article
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Contraception
                Female Contraception
                People and Places
                Population Groupings
                Age Groups
                Children
                Adolescents
                People and Places
                Population Groupings
                Families
                Children
                Adolescents
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Mood Disorders
                Depression
                Biology and Life Sciences
                Psychology
                Addiction
                Addicts
                Drug Users
                Social Sciences
                Psychology
                Addiction
                Addicts
                Drug Users
                People and places
                Geographical locations
                Europe
                European Union
                Sweden
                People and Places
                Population Groupings
                Age Groups
                Adults
                Medicine and Health Sciences
                Neurology
                Epilepsy
                Custom metadata
                The data are available from the Swedish Authorities (National Board of Health and Welfare and Statistics Sweden). Register data is protected by strict confidentiality (Secrecy Act, http://www.government.se/information-material/2009/09/public-access-to-information-and-secrecy-act/) but can be made available for research after a special review that includes approval of the research project by both an Ethics Committee and the authorities’ own data safety committees. The National Board of Health and Welfare is a government agency under the Ministry of Health and Social Affairs. It is not their policy to provide individual level data to researchers abroad. Instead, they normally advice researchers in other countries to cooperate with Swedish colleagues, to whom they can provide data according to standard legal provisions and procedures. Data from the Swedish prescribed drug register have legal restrictions prohibiting the authors from making the minimal data set publicly. The data is available upon request from the Swedish National Board of Health and Welfare following a presentation of an appropriate project description and ethical permit. Researchers can contact Sara Segelson ( sara.segelson@ 123456socialstyrelsen.se ) for more information. For information please see: http://www.socialstyrelsen.se/register/halsodataregister/lakemedelsregistret.

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