Association between Oral Contraceptive Usage and Depressive Symptoms in Korean Women

Association between Oral Contraceptive Usage and Depressive Symptoms in Korean Women | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association between Oral Contraceptive Usage and Depressive Symptoms in Korean Women Sorah Park, Eun-Cheol Park This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6195109/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Oral contraceptives—widely used by women for both reproductive and non-reproductive health reasons such as menstrual regulation, mood stabilization, and acne treatment—vary in type (including combined estrogen-progesterone, progesterone-only, and continuous use oral contraceptives). Usage of oral contraceptives can involve potential negative side effects. Mood changes are among these effects, including depressive symptoms. This study aims to address the gap in research on side effects of oral contraceptives by examining the association between oral contraceptive use and depressive symptoms in adult women in South Korea. Methods This study used data from 2007–2022 from the Korea National Health and Nutrition Examination Survey (KNHANES). Focusing on female respondents aged 18 and older, the final analysis included 15,000 women. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9). The main independent variable was oral contraceptive use for longer than one month. A multiple logistic regression model assessed the association between contraceptive usage and depressive symptoms, presenting results as adjusted odds ratios (aORs) and a significance threshold of p < 0.05. All analyses were conducted using SAS version 9.4. Results Of the 15,000 respondents, 2,573 women reported oral contraceptive usage for longer than a month. Among non-users, 6.3% had depressive symptoms, compared to 9.7% of women who reported using oral contraceptives. Women using contraceptives for over a month had higher odds of reporting depressive symptoms (OR = 1.65, 95% CI 1.37–1.98). Subgroup analyses showed elevated odds for depressive symptoms across various demographic categories, with unmarried women (aOR = 2.20) and those without pregnancy experience (aOR = 2.03) showing notably higher risks (compared with married women aOR = 1.42, and women with pregnancy experience aOR = 1.45). The multiple logistic regression also indicated that women who reported using oral contraceptives for one month or longer were more likely to experience moderate to very severe depressive symptoms, with statistically significant associations found only for moderate and higher depressive symptom levels (aORs ranging from 1.66 to 1.92). Conclusion The study found that women using oral contraceptives were at higher risk for depressive symptoms. Subgroup analyses suggested that of these women, unmarried women and women without pregnancy experience were at highest risk for developing depressive symptoms. This suggests that healthcare systems should monitor women using oral contraceptives and patients should be advised to consider the possibility of depressive symptoms. Introduction Oral contraceptives, commonly also referred to as the birth control pill, are used by millions of women worldwide (Sharma et al., 2020 ). Many women begin to use oral contraceptives during adolescence for reproductive purposes and reasons besides reproductive purposes, such as regulation of their menstrual cycle, regulation of mood, and improvement of skin conditions such as acne (Sharma et al., 2020 ). Oral contraceptive pills can be divided into three categories that are prescribed for these issues, including: combined estrogen-progesterone pills, progesterone-only, and continuous or extended-use pills (Cooper & Patel, 2017 ). Despite the wide usage of oral contraceptives, the negative side effects of oral contraceptive usage are not completely understood, and often controversial. Side effects can be varying due to personal health histories and variation can also exist due to type of contraceptive used. Many more severe side effects, such as increased risk of breast or ovarian cancer, are not widely understood and also not well-known amongst women using these pills (Hunter et al., 2010 ; Sihvo et al., 1998 ; Vessey & Yeates, 2013 ). Discourse on usage of oral contraceptives and their side effects, along with health education for women, is lacking (Hall et al., 2013 ). Ironically, lack of knowledge about oral contraceptives has been shown to be associated with continuation of oral contraception usage – which could exacerbate and increase the severity of symptoms for many women (Stidham et al., 2014). Out of the multiple potential side effects of oral contraception usage, previously reported side effects commonly but not definitively include acne, amenorrhea, breakthrough bleeding, breast tenderness, decreased libido, depression, headache, heavy menses, hirsutism, increased vaginal discharge, irregular menses, nausea, oily skin, and weight gain (Barr, 2010 ; Hee et al., 2013 ). Out of these symptoms, one of the more controversial and less understood potential side effects of oral contraceptives is depression (Kulkarni, 2007 ; O'Connell et al., 2007 ). However, depression may be considered as one of the more alarming side effects to understand about oral contraceptives, as women have generally twice the risk of depressive disorders as men (Kessler, 2003 ; Kessler et al., 1993 ). Hormonal contraception can influence and regulate levels of estrogen and progesterone. These hormones are linked to serotonin availability which can directly impact female mood disorders during premenstrual time periods, pregnancy, postpartum, and during menopause (Lokuge et al., 2011 ). Previous studies that overview oral contraceptives as increasing risk of depression for women have conflicting and inconsistent results (Johansson et al., 2023 ). These inconsistencies may be partially due to studies omitting women who may discontinue the usage of oral contraceptives if they observe adverse effects, leading to healthy user bias in other studies on the side effects of oral contraceptives (Johansson et al., 2023 ). Further, previous research typically studies adolescent female populations. While some studies of these adolescent populations conclude that there is no relationship between oral contraceptives and depression, other studies conclude that oral contraceptive pill usage may increase risk of depression later in life, or directly correlate to depression during time of usage (de Wit et al., 2020 ; McKetta & Keyes, 2018 ). Studies understanding oral contraceptive usage and depression as a potential side effect are similarly conflicting for adult women, and scarcer in number. Previous studies overviewing depressive symptoms in adult women who used oral contraceptives suggest that these symptoms may be more strongly correlated to socioeconomic factors (Gawronska et al., 2024 ). A 2016 national study in Denmark, however, suggested strong correlation between depression and oral contraception usage (Skovlund et al., 2016 ). Considering the importance of understanding depression and contraception usage in greater populations of women, and past conflicting data results, this study aims to understand the correlation between depressive symptoms and oral contraception usage in women in South Korea. Materials and Methods Data This study used annual data from 2007 to 2022 from the Korea National Health and Nutrition Examination Survey (KNHANES). Conducted by the Korea Centers for Disease Control and Prevention, KNHANES is a national surveillance system that has been used to assess the health and nutritional status of Koreans. The survey is based on the National Health Promotion Act, and is a nationally representative cross-sectional survey that includes around 10,000 individuals each year as a survey sample – collecting information on socioeconomic status, health-related behaviors, quality of life, healthcare status and utilization, profiles for disease, and dietary intake (Kweon et al., 2014 ). Participants/Study Population The total number of participants from 2007 to 2022 from the KNHANES was 126,446. Of these respondents, all men were removed in the data analysis, leaving 68,887 women. Only women aged 18 years and above were included in the analysis. Women with missing responses for each survey item were excluded from the data, which left 15,000 total women in the final analysis. Variables The dependent variable, depressive symptoms, was categorized by levels of severity. These categories were based on the Patient Health Questionnaire 9-item depression scale (PHQ-9). The PHQ-9 scale consists of nine items that allow clinicians to flag symptoms of depression and the severity of these. The summation of the nine items in the PHQ-9 scale are added together and the cut-points are 5, 10, 15, and 20, which respectively represent thresholds for mild, moderate, moderately severe, and severe depressive symptoms (Kroenke, 2021 ). Scores greater than or equal to10 are cause for potential clinical diagnosis of depression, while scores below 10 represent a “gray zone” that requires a more detailed examination (Kroenke et al., 2001 ). As a result, the data analysis in this study divided PHQ-9 scores below 10 as nonexistent/minimal depressive symptoms and scores greater than or equal to 10 as existent depressive symptoms – divided as “no” and “yes” depressive categories in the study. The primary independent variable of interest was usage of oral contraceptives for longer than one month. The question in the KNHANES asked women if they had used any type of oral contraceptive pill for longer than one month. Respondents were able to respond with a “yes” or “no” answer (Kweon et al., 2014 ). The direct translation for this question translates specifically to “usage of birth control pill,” implying usage of oral contraceptives primarily for birth control. Covariates included various sociodemographic factors such as marriage status, pregnancy experience, age, income, perceived stress levels, education level, health insurance status, personal health perception, employment status, category of employment (if employed), and physical activity. Statistical Analyses Statistical analysis of the KNHANES survey data was performed using SAS version 9.4 (SAS Inc., Cary, NC, USA). A multiple logistic regression model was used to examine the relationship between oral contraceptive usage and depressive symptoms. Depressive symptoms were categorized into “minimal/nonexistent” and “existent” groups and labeled as “No” and “Yes” depressive symptoms, respectively. Statistical significance was determined with a threshold p-value of < 0.05, and results were presented as adjusted odds ratios (aORs) with 95% confidence intervals (CI). An aOR of 1.00 indicated no effect. Results Table 1 presents the data from the 15,000 responses from women in the multiple regression analysis, categorized by marriage status, pregnancy experience, age, and other independent variables. Among the total responses, there were 12,427 women who reported not using any oral contraceptive pill for longer than a month, and 2,573 women who reported using oral contraceptives for longer than a month. Of the women who did not use any contraceptive, 93.7% had minimal/nonexistent depressive symptoms and 6.3% reported significant levels of depressive symptoms. Of the women who did use oral contraceptives for longer than a month, 90.3% had minimal/nonexistent levels of depressive symptoms, while 9.7% reported significant levels of depressive symptoms. Table 2 displays the odds ratios for the association between oral contraceptive pill usage and depressive symptoms, as well as other relevant factors. Among the women surveyed, those who had taken oral contraceptive pills for longer than a month had a higher chance of significant levels of depressive symptoms. Specifically, the odds ratio for depressive symptoms was 1.65 (95% CI 1.37–1.98). Marriage status or pregnancy status did not have any statistical significance in increasing score on the PHQ-9 scale. Table 3 presents the results of subgroup analyses categorized by oral contraceptive pill usage. For women who had used oral contraceptive pills for longer than a month, depressive symptoms were associated with increased odds for both married and unmarried women, and women with both pregnancy experience and no pregnancy experience. These subgroup analyses were of particular concern because marriage status and pregnancy experience were predicted to be factors that may have a large influence on oral contraception usage or lifestyle factors (Cho et al., 2012; Kim et al., 2024). The aORs for married and unmarried women who used oral contraceptive pills with depressive symptoms were 2.20 (95% CI 1.42 – 3.40) for married women and 1.42 (95% CI 1.17–1.73) for unmarried women. For pregnancy experience, the aORs for women with depressive symptoms were 2.03 (95% CI 1.28–3.21) for women without pregnancy experience and 1.45 (95% CI 1.20–1.76) for women with pregnancy experience. Statistically significant associations with odds ratios greater than 1.00 were found for at least one category of all other independent confounding variables for women who had taken the pill for longer than a month who had significant levels of depressive symptoms. Table 4 displays the results of a multiple logistic regression analysis examining the relationship between oral contraceptive pill usage and depressive symptoms using the PHQ-9 scale. The analysis revealed that women who reported using oral contraceptives for a month of longer generally exhibited increased odds of depressive symptom scores greater than or equal to 10 (moderate, moderately severe, and very severe levels of depressive symptoms). There was no statistical significance for reporting mild depressive symptoms in association with using oral contraceptive pills. Specifically, the aORs for women who had used oral contraceptives who had moderate scores of depressive symptoms was 1.66 (95% CI 1.31–2.11), moderately severe levels of depressive symptoms was 1.69 (95% CI 1.21–2.37), and very severe levels of depressive symptoms was 1.92 (95% CI 1.10–3.36). Discussion This study suggests a statistically significant association between oral contraceptive usage for longer than a month and depressive symptoms according to the PHQ-9 Scale (≥ 10). Data analysis suggested that women who have used a form of oral contraceptives for a month or longer were 1.65 (95% CI 1.47–1.98) times more likely to report significant levels of depressive symptoms. Specifically, the results of the analysis suggested that the chances of moderate scores of depressive symptoms were 1.66 (95% CI 1.31–2.11), moderately severe levels of depressive symptoms were 1.69 (95% CI 1.21–2.37), and very severe levels of depressive symptoms were 1.92 (95% CI 1.10–3.36). These statistical analyses may indicate that use of oral contraceptives, particularly prolonged use, can increase risk for depressive symptoms in women. These results also align with previous research studies that suggests that hormonal contraception, particularly for adolescents, is associated with antidepressant use and earlier diagnosis of depression (Skovlund et al., 2016 ; Wit et al., 2020 ). On the other hand, these results conflict with research that suggests that hormonal oral contraceptive can have beneficial effects on psychopathology in women, possibly reducing levels of depression through hormonal control and stabilization (Keyes et al., 2013 ; Toffol et al., 2011 ). The discrepancies in these studies may be a result of the population women surveyed, along with the conditions of the study that can include health bias in results if women who saw adverse side effects to oral contraceptives stopped using the pills and were unable to participate in the study at the time. While the analysis of this study did not see wide variance between populations of women by age, as all age groups saw greater than 1.00 odds of developing depressive symptoms with oral contraception usage, data suggested lesser odds for older age groups. As subgroup analyses also suggested that unmarried women and women without pregnancy experience are also at greatest risk for depressive symptoms in association with oral contraception usage, this study with South Korean women therefore further brings to attention that younger women may be more vulnerable to developing symptoms of depression with oral contraceptive pill usage. A great amount of stigma exists around usage of oral contraceptives as a tool that can be used for sexual freedom for women (Hur, 2013 ; Sharma et al., 2020 ). Such stigma in more conservative societies like South Korea can accentuate the lack of conversation around the side effects of hormonal contraception that should be considered before it is prescribed (Lee et al., 2011 ; Lim & Cho, 2002 ). Discussion around the impact of oral contraception on women’s health becomes further difficult when it is considered how usage of oral contraceptive pills has been socially constructed to be seen as a woman’s choice, when in some cases, contraception is not used for oral contraceptive but to treat hormone-related symptoms, or when the pill becomes the only option for women to maintain a healthy sexual life (Granzow, 2007 ). This study also has several limitations. As a cross-sectional study, data is limited to the annual results from 2007–2022 and cannot suggest clear causation of depressive symptoms as a side effect of oral contraception usage. Because the KNHANES also consists of self-reported data, it additionally introduces potential personal biases, including the possibility of women possibly not wanting to report oral contraceptive pill usage due to potential perceived stigma. Personal bias may alternatively exist if there were women not wanting to report depressive symptoms if they are not clinically diagnosed, or due to existing stigma against depression. It is also possible for the study to have healthy bias, as women who used oral contraceptives in the past and observed negative side effects would report in the survey that they are not currently using the pill regardless of their existing depressive symptoms or lack of depressive symptoms. Furthermore, use of oral contraception and reporting values for the PHQ-9 scale included in the KNHANES study are extremely individualistic, as some women may use forms of hormonal contraception but not for the purpose of birth control as worded in the survey. The results of the study therefore are unable to stratify for types of oral contraception that may be used by South Korean women and likely excludes a large base of data of women who use oral contraception for non-oral contraceptive related reasons. As a result, this study was also unable to stratify for type of oral contraceptive used, length of usage, or reason for usage – as the only given question in the survey asked women if they had used oral contraceptive for one month or longer. Lack of more detailed questioning in the national survey could be due to lack of awareness of the potential serious side effects of oral contraceptives, as well as social stigmas that exist around these topics in women’s health. In conclusion, the statistically significant association between depressive symptoms and oral contraceptive usage suggests that further research is needed to understand the potential adverse effects of oral contraceptives. With so many women who use oral contraceptive pills, it is imperative to understand from a public health perspective how hormonal contraception can affect women’s health. Many women start oral contraceptives from a young age, which can also potentially accelerate and amplify the side effects that they feel from hormonal oral contraceptives. Conclusion These results of this study show a statistically significant association between use of oral contraceptives for longer than one month and elevated risk of depressive symptoms. Women using the pill for over a month were associated with experiencing higher odds of depressive symptoms across varying severity levels. These findings align with research linking hormonal contraception to depression, particularly among younger women, though they diverge from studies suggesting mood-stabilizing benefits. The association seen here highlights the need for awareness and further research into the mental health impacts of contraceptive use, especially considering the young age at which many women begin using oral contraceptives. Given the potential for unreported adverse effects due to social stigma or discontinuation, more longitudinal studies are warranted to clarify these risks and inform healthcare practices, ensuring that women receive balanced information on contraceptive choices. Declarations Ethical Approval Not Applicable. The KNHANES survey data that this study used, however, was completed with IRB approval and followed the Helsinki Declaration, the Bioethics and Safety Act of Korea, and the Personal Information Protection Act of Korea. Funding Not applicable. Human Ethics and Consent to Participate declarations : not applicable References Barr NG. Managing adverse effects of hormonal contraceptives. Am Family Phys. 2010;82(12):1499–506. https://pubmed.ncbi.nlm.nih.gov/21166370/ . Cho I, Ahn S, Kim SY, Park YS, Kim HW, Lee SO, Lee SH, Chung CW. Depression of Married and Employed Women Based on Social-Role Theory. J Korean Acad Nurs. 2012;42(4):496–507. https://doi.org/10.4040/jkan.2012.42.4.496 . 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Wit Ad, Booij S, Giltay E, Joffe H, Schoevers R, Oldehinkel A. Association of Use of Oral Contraceptives With Depressive Symptoms Among Adolescents and Young Women. JAMA Psychiatry. 2020;77(1):52–9. https://doi.org/10.1001/jamapsychiatry.2019.2838 . Tables Tables 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Tables.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6195109","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":443800412,"identity":"2202040c-f4e7-4d3e-ae33-905d4994803d","order_by":0,"name":"Sorah Park","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYJACZhAhwcx8wOADA0MCCVrY2RIKZ5CmhZ/H4DMPMVrk23sffi7cYZcv2cxguNm27XCefAPzww/4tBicOW4sPfNMsuVsZoZk49y2w8UGB9iMJfBqkUhjkOZtYzaQY2Y4BtKSuIGBwQy/w2akMf/mbasHamFs/20J1DK/gf0bfs/cSGMD2nLYQJqZmcGYEail4QAPflsMzhxjs+Y9c9xAspmNwbDnXHrihsM8xXj9It/exnybd0e1gcT58x8MfpRZJ85vb9+IN8TAgLEBxmBjgEYT0VoY/hCjfBSMglEwCkYaAADEzUUapQniBgAAAABJRU5ErkJggg==","orcid":"","institution":"Yonsei University","correspondingAuthor":true,"prefix":"","firstName":"Sorah","middleName":"","lastName":"Park","suffix":""},{"id":443800413,"identity":"d4bdcb2c-1fd5-4eb6-9d7c-21cb92f7db04","order_by":1,"name":"Eun-Cheol Park","email":"","orcid":"","institution":"Yonsei University","correspondingAuthor":false,"prefix":"","firstName":"Eun-Cheol","middleName":"","lastName":"Park","suffix":""}],"badges":[],"createdAt":"2025-03-10 11:38:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6195109/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6195109/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90881030,"identity":"ff438424-8aab-44fe-b3b4-678087351add","added_by":"auto","created_at":"2025-09-09 09:39:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":374474,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6195109/v1/fbcc3ccd-bfa1-46f9-ac66-bdb56620a8c2.pdf"},{"id":80920067,"identity":"e50df9b5-14a6-4bb3-846d-50a6af5543f6","added_by":"auto","created_at":"2025-04-18 19:55:49","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":42265,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-6195109/v1/2b8bd0038799ce62faac5fb7.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association between Oral Contraceptive Usage and Depressive Symptoms in Korean Women","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOral contraceptives, commonly also referred to as the birth control pill, are used by millions of women worldwide (Sharma et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Many women begin to use oral contraceptives during adolescence for reproductive purposes and reasons besides reproductive purposes, such as regulation of their menstrual cycle, regulation of mood, and improvement of skin conditions such as acne (Sharma et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Oral contraceptive pills can be divided into three categories that are prescribed for these issues, including: combined estrogen-progesterone pills, progesterone-only, and continuous or extended-use pills (Cooper \u0026amp; Patel, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Despite the wide usage of oral contraceptives, the negative side effects of oral contraceptive usage are not completely understood, and often controversial. Side effects can be varying due to personal health histories and variation can also exist due to type of contraceptive used. Many more severe side effects, such as increased risk of breast or ovarian cancer, are not widely understood and also not well-known amongst women using these pills (Hunter et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2010\u003c/span\u003e; Sihvo et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e1998\u003c/span\u003e; Vessey \u0026amp; Yeates, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Discourse on usage of oral contraceptives and their side effects, along with health education for women, is lacking (Hall et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Ironically, lack of knowledge about oral contraceptives has been shown to be associated with continuation of oral contraception usage \u0026ndash; which could exacerbate and increase the severity of symptoms for many women (Stidham et al., 2014).\u003c/p\u003e \u003cp\u003eOut of the multiple potential side effects of oral contraception usage, previously reported side effects commonly but not definitively include acne, amenorrhea, breakthrough bleeding, breast tenderness, decreased libido, depression, headache, heavy menses, hirsutism, increased vaginal discharge, irregular menses, nausea, oily skin, and weight gain (Barr, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2010\u003c/span\u003e; Hee et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Out of these symptoms, one of the more controversial and less understood potential side effects of oral contraceptives is depression (Kulkarni, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; O'Connell et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2007\u003c/span\u003e). However, depression may be considered as one of the more alarming side effects to understand about oral contraceptives, as women have generally twice the risk of depressive disorders as men (Kessler, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2003\u003c/span\u003e; Kessler et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e1993\u003c/span\u003e). Hormonal contraception can influence and regulate levels of estrogen and progesterone. These hormones are linked to serotonin availability which can directly impact female mood disorders during premenstrual time periods, pregnancy, postpartum, and during menopause (Lokuge et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). Previous studies that overview oral contraceptives as increasing risk of depression for women have conflicting and inconsistent results (Johansson et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). These inconsistencies may be partially due to studies omitting women who may discontinue the usage of oral contraceptives if they observe adverse effects, leading to healthy user bias in other studies on the side effects of oral contraceptives (Johansson et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurther, previous research typically studies adolescent female populations. While some studies of these adolescent populations conclude that there is no relationship between oral contraceptives and depression, other studies conclude that oral contraceptive pill usage may increase risk of depression later in life, or directly correlate to depression during time of usage (de Wit et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; McKetta \u0026amp; Keyes, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Studies understanding oral contraceptive usage and depression as a potential side effect are similarly conflicting for adult women, and scarcer in number. Previous studies overviewing depressive symptoms in adult women who used oral contraceptives suggest that these symptoms may be more strongly correlated to socioeconomic factors (Gawronska et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). A 2016 national study in Denmark, however, suggested strong correlation between depression and oral contraception usage (Skovlund et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eConsidering the importance of understanding depression and contraception usage in greater populations of women, and past conflicting data results, this study aims to understand the correlation between depressive symptoms and oral contraception usage in women in South Korea.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData\u003c/h2\u003e \u003cp\u003eThis study used annual data from 2007 to 2022 from the Korea National Health and Nutrition Examination Survey (KNHANES). Conducted by the Korea Centers for Disease Control and Prevention, KNHANES is a national surveillance system that has been used to assess the health and nutritional status of Koreans. The survey is based on the National Health Promotion Act, and is a nationally representative cross-sectional survey that includes around 10,000 individuals each year as a survey sample \u0026ndash; collecting information on socioeconomic status, health-related behaviors, quality of life, healthcare status and utilization, profiles for disease, and dietary intake (Kweon et al., \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2014\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants/Study Population\u003c/h3\u003e\n\u003cp\u003eThe total number of participants from 2007 to 2022 from the KNHANES was 126,446. Of these respondents, all men were removed in the data analysis, leaving 68,887 women. Only women aged 18 years and above were included in the analysis. Women with missing responses for each survey item were excluded from the data, which left 15,000 total women in the final analysis.\u003c/p\u003e\n\u003ch3\u003eVariables\u003c/h3\u003e\n\u003cp\u003eThe dependent variable, depressive symptoms, was categorized by levels of severity. These categories were based on the Patient Health Questionnaire 9-item depression scale (PHQ-9). The PHQ-9 scale consists of nine items that allow clinicians to flag symptoms of depression and the severity of these. The summation of the nine items in the PHQ-9 scale are added together and the cut-points are 5, 10, 15, and 20, which respectively represent thresholds for mild, moderate, moderately severe, and severe depressive symptoms (Kroenke, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Scores greater than or equal to10 are cause for potential clinical diagnosis of depression, while scores below 10 represent a \u0026ldquo;gray zone\u0026rdquo; that requires a more detailed examination (Kroenke et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2001\u003c/span\u003e). As a result, the data analysis in this study divided PHQ-9 scores below 10 as nonexistent/minimal depressive symptoms and scores greater than or equal to 10 as existent depressive symptoms \u0026ndash; divided as \u0026ldquo;no\u0026rdquo; and \u0026ldquo;yes\u0026rdquo; depressive categories in the study.\u003c/p\u003e \u003cp\u003eThe primary independent variable of interest was usage of oral contraceptives for longer than one month. The question in the KNHANES asked women if they had used any type of oral contraceptive pill for longer than one month. Respondents were able to respond with a \u0026ldquo;yes\u0026rdquo; or \u0026ldquo;no\u0026rdquo; answer (Kweon et al., \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). The direct translation for this question translates specifically to \u0026ldquo;usage of birth control pill,\u0026rdquo; implying usage of oral contraceptives primarily for birth control.\u003c/p\u003e \u003cp\u003eCovariates included various sociodemographic factors such as marriage status, pregnancy experience, age, income, perceived stress levels, education level, health insurance status, personal health perception, employment status, category of employment (if employed), and physical activity.\u003c/p\u003e\n\u003ch3\u003eStatistical Analyses\u003c/h3\u003e\n\u003cp\u003eStatistical analysis of the KNHANES survey data was performed using SAS version 9.4 (SAS Inc., Cary, NC, USA). A multiple logistic regression model was used to examine the relationship between oral contraceptive usage and depressive symptoms. Depressive symptoms were categorized into \u0026ldquo;minimal/nonexistent\u0026rdquo; and \u0026ldquo;existent\u0026rdquo; groups and labeled as \u0026ldquo;No\u0026rdquo; and \u0026ldquo;Yes\u0026rdquo; depressive symptoms, respectively. Statistical significance was determined with a threshold p-value of \u0026lt;\u0026thinsp;0.05, and results were presented as adjusted odds ratios (aORs) with 95% confidence intervals (CI). An aOR of 1.00 indicated no effect.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTable 1 presents the data from the 15,000 responses from women in the multiple regression analysis, categorized by marriage status, pregnancy experience, age, and other independent variables. Among the total responses, there were 12,427 women who reported not using any oral contraceptive pill for longer than a month, and 2,573 women who reported using oral contraceptives for longer than a month. Of the women who did not use any contraceptive, 93.7% had minimal/nonexistent depressive symptoms and 6.3% reported significant levels of depressive symptoms. Of the women who did use oral contraceptives for longer than a month, 90.3% had minimal/nonexistent levels of depressive symptoms, while 9.7% reported significant levels of depressive symptoms.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 displays the odds ratios for the association between oral contraceptive pill usage and depressive symptoms, as well as other relevant factors. Among the women surveyed, those who had taken oral contraceptive pills for longer than a month had a higher chance of significant levels of depressive symptoms. Specifically, the odds ratio for depressive symptoms was 1.65 (95% CI 1.37–1.98). Marriage status or pregnancy status did not have any statistical significance in increasing score on the PHQ-9 scale.\u003c/p\u003e\n\u003cp\u003eTable 3 presents the results of subgroup analyses categorized by oral contraceptive pill usage. For women who had used oral contraceptive pills for longer than a month, depressive symptoms were associated with increased odds for both married and unmarried women, and women with both pregnancy experience and no pregnancy experience. These subgroup analyses were of particular concern because marriage status and pregnancy experience were predicted to be factors that may have a large influence on oral contraception usage or lifestyle factors (Cho et al., 2012; Kim et al., 2024). The aORs for married and unmarried women who used oral contraceptive pills with depressive symptoms were 2.20 (95% CI 1.42 – 3.40) for married women and 1.42 (95% CI 1.17–1.73) for unmarried women. For pregnancy experience, the aORs for women with depressive symptoms were 2.03 (95% CI 1.28–3.21) for women without pregnancy experience and 1.45 (95% CI 1.20–1.76) for women with pregnancy experience. Statistically significant associations with odds ratios greater than 1.00 were found for at least one category of all other independent confounding variables for women who had taken the pill for longer than a month who had significant levels of depressive symptoms.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4 displays the results of a multiple logistic regression analysis examining the relationship between oral contraceptive pill usage and depressive symptoms using the PHQ-9 scale. The analysis revealed that women who reported using oral contraceptives for a month of longer generally exhibited increased odds of depressive symptom scores greater than or equal to 10 (moderate, moderately severe, and very severe levels of depressive symptoms). There was no statistical significance for reporting mild depressive symptoms in association with using oral contraceptive pills. Specifically, the aORs for women who had used oral contraceptives who had moderate scores of depressive symptoms was 1.66 (95% CI 1.31–2.11), moderately severe levels of depressive symptoms was 1.69 (95% CI 1.21–2.37), and very severe levels of depressive symptoms was 1.92 (95% CI 1.10–3.36).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study suggests a statistically significant association between oral contraceptive usage for longer than a month and depressive symptoms according to the PHQ-9 Scale (\u0026ge;\u0026thinsp;10). Data analysis suggested that women who have used a form of oral contraceptives for a month or longer were 1.65 (95% CI 1.47\u0026ndash;1.98) times more likely to report significant levels of depressive symptoms. Specifically, the results of the analysis suggested that the chances of moderate scores of depressive symptoms were 1.66 (95% CI 1.31\u0026ndash;2.11), moderately severe levels of depressive symptoms were 1.69 (95% CI 1.21\u0026ndash;2.37), and very severe levels of depressive symptoms were 1.92 (95% CI 1.10\u0026ndash;3.36). These statistical analyses may indicate that use of oral contraceptives, particularly prolonged use, can increase risk for depressive symptoms in women.\u003c/p\u003e \u003cp\u003eThese results also align with previous research studies that suggests that hormonal contraception, particularly for adolescents, is associated with antidepressant use and earlier diagnosis of depression (Skovlund et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Wit et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). On the other hand, these results conflict with research that suggests that hormonal oral contraceptive can have beneficial effects on psychopathology in women, possibly reducing levels of depression through hormonal control and stabilization (Keyes et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Toffol et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). The discrepancies in these studies may be a result of the population women surveyed, along with the conditions of the study that can include health bias in results if women who saw adverse side effects to oral contraceptives stopped using the pills and were unable to participate in the study at the time. While the analysis of this study did not see wide variance between populations of women by age, as all age groups saw greater than 1.00 odds of developing depressive symptoms with oral contraception usage, data suggested lesser odds for older age groups. As subgroup analyses also suggested that unmarried women and women without pregnancy experience are also at greatest risk for depressive symptoms in association with oral contraception usage, this study with South Korean women therefore further brings to attention that younger women may be more vulnerable to developing symptoms of depression with oral contraceptive pill usage.\u003c/p\u003e \u003cp\u003eA great amount of stigma exists around usage of oral contraceptives as a tool that can be used for sexual freedom for women (Hur, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Sharma et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Such stigma in more conservative societies like South Korea can accentuate the lack of conversation around the side effects of hormonal contraception that should be considered before it is prescribed (Lee et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2011\u003c/span\u003e; Lim \u0026amp; Cho, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). Discussion around the impact of oral contraception on women\u0026rsquo;s health becomes further difficult when it is considered how usage of oral contraceptive pills has been socially constructed to be seen as a woman\u0026rsquo;s choice, when in some cases, contraception is not used for oral contraceptive but to treat hormone-related symptoms, or when the pill becomes the only option for women to maintain a healthy sexual life (Granzow, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2007\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study also has several limitations. As a cross-sectional study, data is limited to the annual results from 2007\u0026ndash;2022 and cannot suggest clear causation of depressive symptoms as a side effect of oral contraception usage. Because the KNHANES also consists of self-reported data, it additionally introduces potential personal biases, including the possibility of women possibly not wanting to report oral contraceptive pill usage due to potential perceived stigma. Personal bias may alternatively exist if there were women not wanting to report depressive symptoms if they are not clinically diagnosed, or due to existing stigma against depression.\u003c/p\u003e \u003cp\u003eIt is also possible for the study to have healthy bias, as women who used oral contraceptives in the past and observed negative side effects would report in the survey that they are not currently using the pill regardless of their existing depressive symptoms or lack of depressive symptoms. Furthermore, use of oral contraception and reporting values for the PHQ-9 scale included in the KNHANES study are extremely individualistic, as some women may use forms of hormonal contraception but not for the purpose of birth control as worded in the survey. The results of the study therefore are unable to stratify for types of oral contraception that may be used by South Korean women and likely excludes a large base of data of women who use oral contraception for non-oral contraceptive related reasons. As a result, this study was also unable to stratify for type of oral contraceptive used, length of usage, or reason for usage \u0026ndash; as the only given question in the survey asked women if they had used oral contraceptive for one month or longer. Lack of more detailed questioning in the national survey could be due to lack of awareness of the potential serious side effects of oral contraceptives, as well as social stigmas that exist around these topics in women\u0026rsquo;s health.\u003c/p\u003e \u003cp\u003eIn conclusion, the statistically significant association between depressive symptoms and oral contraceptive usage suggests that further research is needed to understand the potential adverse effects of oral contraceptives. With so many women who use oral contraceptive pills, it is imperative to understand from a public health perspective how hormonal contraception can affect women\u0026rsquo;s health. Many women start oral contraceptives from a young age, which can also potentially accelerate and amplify the side effects that they feel from hormonal oral contraceptives.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThese results of this study show a statistically significant association between use of oral contraceptives for longer than one month and elevated risk of depressive symptoms. Women using the pill for over a month were associated with experiencing higher odds of depressive symptoms across varying severity levels. These findings align with research linking hormonal contraception to depression, particularly among younger women, though they diverge from studies suggesting mood-stabilizing benefits. The association seen here highlights the need for awareness and further research into the mental health impacts of contraceptive use, especially considering the young age at which many women begin using oral contraceptives. Given the potential for unreported adverse effects due to social stigma or discontinuation, more longitudinal studies are warranted to clarify these risks and inform healthcare practices, ensuring that women receive balanced information on contraceptive choices.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003eThe KNHANES survey data that this study used, however, was completed with IRB approval and followed the Helsinki Declaration, the Bioethics and Safety Act of Korea, and the Personal Information Protection Act of Korea.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations\u003c/strong\u003e: not applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBarr NG. Managing adverse effects of hormonal contraceptives. Am Family Phys. 2010;82(12):1499\u0026ndash;506. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/21166370/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/21166370/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCho I, Ahn S, Kim SY, Park YS, Kim HW, Lee SO, Lee SH, Chung CW. Depression of Married and Employed Women Based on Social-Role Theory. J Korean Acad Nurs. 2012;42(4):496\u0026ndash;507. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4040/jkan.2012.42.4.496\u003c/span\u003e\u003cspan address=\"10.4040/jkan.2012.42.4.496\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCooper DB, Patel P. (2017). 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J Clin Psychiatry. 2011;72(11):e1563\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4088/JCP.11com07089\u003c/span\u003e\u003cspan address=\"10.4088/JCP.11com07089\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcKetta S, Keyes KM. Oral Contraceptive Use and Depression Among Adolescents. Ann Epidemiol. 2018;29:46\u0026ndash;51. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.annepidem.2018.10.002\u003c/span\u003e\u003cspan address=\"10.1016/j.annepidem.2018.10.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO'Connell K, Davis AR, Kerns J. Oral contraceptives: side effects and depression in adolescent girls. 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JAMA Psychiatry. 2020;77(1):52\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/jamapsychiatry.2019.2838\u003c/span\u003e\u003cspan address=\"10.1001/jamapsychiatry.2019.2838\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6195109/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6195109/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOral contraceptives\u0026mdash;widely used by women for both reproductive and non-reproductive health reasons such as menstrual regulation, mood stabilization, and acne treatment\u0026mdash;vary in type (including combined estrogen-progesterone, progesterone-only, and continuous use oral contraceptives). Usage of oral contraceptives can involve potential negative side effects. Mood changes are among these effects, including depressive symptoms. This study aims to address the gap in research on side effects of oral contraceptives by examining the association between oral contraceptive use and depressive symptoms in adult women in South Korea.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis study used data from 2007\u0026ndash;2022 from the Korea National Health and Nutrition Examination Survey (KNHANES). Focusing on female respondents aged 18 and older, the final analysis included 15,000 women. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9). The main independent variable was oral contraceptive use for longer than one month. A multiple logistic regression model assessed the association between contraceptive usage and depressive symptoms, presenting results as adjusted odds ratios (aORs) and a significance threshold of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All analyses were conducted using SAS version 9.4.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf the 15,000 respondents, 2,573 women reported oral contraceptive usage for longer than a month. Among non-users, 6.3% had depressive symptoms, compared to 9.7% of women who reported using oral contraceptives. Women using contraceptives for over a month had higher odds of reporting depressive symptoms (OR\u0026thinsp;=\u0026thinsp;1.65, 95% CI 1.37\u0026ndash;1.98). Subgroup analyses showed elevated odds for depressive symptoms across various demographic categories, with unmarried women (aOR\u0026thinsp;=\u0026thinsp;2.20) and those without pregnancy experience (aOR\u0026thinsp;=\u0026thinsp;2.03) showing notably higher risks (compared with married women aOR\u0026thinsp;=\u0026thinsp;1.42, and women with pregnancy experience aOR\u0026thinsp;=\u0026thinsp;1.45). The multiple logistic regression also indicated that women who reported using oral contraceptives for one month or longer were more likely to experience moderate to very severe depressive symptoms, with statistically significant associations found only for moderate and higher depressive symptom levels (aORs ranging from 1.66 to 1.92).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe study found that women using oral contraceptives were at higher risk for depressive symptoms. Subgroup analyses suggested that of these women, unmarried women and women without pregnancy experience were at highest risk for developing depressive symptoms. This suggests that healthcare systems should monitor women using oral contraceptives and patients should be advised to consider the possibility of depressive symptoms.\u003c/p\u003e","manuscriptTitle":"Association between Oral Contraceptive Usage and Depressive Symptoms in Korean Women","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-18 19:55:44","doi":"10.21203/rs.3.rs-6195109/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f125658f-9c79-4ae7-9b4a-730fa9f2c509","owner":[],"postedDate":"April 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-09T09:39:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-18 19:55:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6195109","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6195109","identity":"rs-6195109","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}