Identifying psychiatric comorbidities that occur following the introduction of hormonal contraception: A Scoping review

Identifying psychiatric comorbidities that occur following the introduction of hormonal contraception: A Scoping review | 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 Systematic Review Identifying psychiatric comorbidities that occur following the introduction of hormonal contraception: A Scoping review Amélie Poirier, Juliette Fortier, Marie-France Marin, Marie Désilets, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7734404/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 Hormonal contraceptives are among the most widely used medications by women of reproductive age yet growing concerns have emerged regarding their potential impact on mental health. While mood-related side effects are frequently reported anecdotally, their prevalence, clinical significance, and relationship to specific contraceptive formulations remain poorly defined. Objective This scoping review aimed to examine the associations between hormonal contraception and psychiatric outcomes, with a focus on depressive symptoms, anxiety, and other mental health disorders. Methods A comprehensive literature search of four major databases was conducted to identify peer-reviewed studies published between 2014 and 2024. Forty-six eligible studies were included, spanning observational cohorts, cross-sectional surveys, and clinical trials. Study quality was appraised using the Joanna Briggs Institute checklist. A meta-analyse were performed with random-effects models and subgroup analyses stratified by hormonal class and psychiatric outcome. Results Pooled data revealed a small but statistically significant association between hormonal contraceptive use (especially progestin-only formulations) and increased risk of depressive symptoms and suicidality. Evidence for associations with anxiety and other psychiatric conditions was less consistent. Methodological heterogeneity, particularly in outcome measurement and control for confounding, was a frequent limitation. Conclusion The findings suggest that hormonal contraception, while highly effective for reproductive health, may contribute to adverse psychiatric outcomes in a subset of users. These results underscore the need for individualized risk assessment, integrated mental health screening in contraceptive care, and future prospective studies using standardized psychiatric endpoints to inform safer, more tailored contraceptive prescribing practices. Clinical trial number: not applicable. Hormonal contraception Oral contraceptive pills Combined oral contraceptives Progestin-only contraception Depression Anxiety Suicidal behavior Mood disorders Women’s mental health Adolescents Figures Figure 1 Figure 2 1. Introduction Hormonal contraceptives (HCs) are amongst the most widely used birth control methods worldwide, providing highly effective unintended pregnancy prevention while also providing additional health benefits, including menstrual cycle regulation, acne management, and a reduced risk of certain gynecological conditions. They are also used in the treatment of premenstrual dysphoric disorder (PMDD) ( 1 ) ( 2 ). According to the United Nations' 2022 global report, approximately 23% of women aged 15 to 49 years utilize short-acting hormonal contraceptives, such as oral contraceptive pills and injectables, while an estimated 19% rely on long-acting hormonal methods, including implants and intrauterine devices ( 3 ). All forms of hormonal contraception, including oral pills, implants, IUDs, intramuscular injections (such as DMPA), vaginal rings and transdermal patches, have been shown to be effective, safe and reversible when used appropriately ( 4 ). However, there is growing interest in understanding their potential psychological effects as some studies have reported associations between hormonal contraception and psychiatric disorders, particularly depression and suicidal ideations ( 5 ) ( 6 ) ( 7 ). Despite the well-established efficacy of hormonal contraceptives in preventing pregnancy and managing other conditions as mentioned above, emerging evidence suggests that exogenous hormone exposure may have neuropsychiatric effects, particularly on mood and anxiety symptoms ( 6 ) ( 7 ). However, the existing literature on this topic remains a subject of debate and seems primarily focused on oral contraceptives, even though women experience a substantially greater burden of psychiatric disorders compared to men, particularly during hormonally sensitive periods such as adolescence and their reproductive years ( 8 ) ( 9 ). Notably, the highest prevalence is observed among young adults aged 18 to 25 ( 8 ). Contraceptives are classified into three main types: short-acting reversible methods (oral contraceptive pills, injectables, patches, and vaginal rings), long-acting reversible methods (IUDs and implants), and permanent methods (female sterilization) ( 2 ). HCs essentially suppress ovulation and modify the endometrial environment. By disrupting the communication within the hypothalamic-pituitary-ovarian axis, these agents suppress the release of gonadotropin-releasing hormone (GnRH). This leads to a decline in both follicle-stimulating hormone (FSH) and luteinizing hormone (LH), effectively halting ovulation ( 7 ). Moreover, the resulting drop in natural progesterone levels makes the uterine environment less suitable for egg implantation ( 7 ). Oral contraceptives (OCs) contain either a combination of estrogen and progestin – synthetic derivatives of the steroid sex hormones estradiol and/or progesterone – or progestin alone. Ethinylestradiol, a synthetic estrogen, acts as an analogue and competitor of endogenous estradiol, while synthetic progestins mimic and compete with natural progesterone ( 1 ) ( 7 ). Progestins are categorized into four generations based on their androgenic activity. These synthetic compounds are derived either from testosterone-specifically, 19-nortestosterone derivatives-or from progesterone, including 17-hydroxyprogesterone and 19-norprogesterone derivatives ( 10 ). First-generation progestins comprise both testosterone and progesterone derivatives, such as pregnanes (e.g., chlormadinone acetate) and estranes (e.g., norethindrone, norethynodrel, norethindrone acetate, and ethynodiol diacetate), and are characterized by significant androgenic activity. Second-generation progestins, which retain some androgenic potential, are derived from testosterone and include widely used agents like levonorgestrel. Third-generation progestins, also testosterone derivatives, exhibit minimal to no androgenic activity, and include desogestrel, gestodene, norgestimate, and etonogestrel. In contrast, fourth-generation progestins possess anti-androgenic properties and include non-ethylated estranes, such as dienogest and drospirenone, as well as 19-norprogesterone derivatives like nomegestrol acetate ( 1 ) ( 10 ). Progestin-only contraceptives (POCs) can be found in the form of pills, implants, intramuscular injections, such as DMPA, and intrauterine devices (IUDs). IUDs mainly work locally by thickening cervical mucus, which creates an unfavorable environment for sperm, reducing the likelihood of fertilization ( 1 ) ( 6 ). While all POCs alter the endometrial lining, the nature and extent of these changes vary depending on the method of delivery and the dosage used ( 1 ). Hormonal contraceptives, irrespective of formulation, produce systemic effects that extend beyond reproductive physiology and may carry broader implications for mental health. The relationship between HC-induced hormonal fluctuations and mental well-being is complex, with some studies linking hormonal contraceptives to psychiatric disorders such as depression and anxiety, while others suggest potential protective effects, particularly in women with pre-existing mental health conditions ( 2 ). Interestingly, new studies have focused specifically on progestin-only contraceptives, some suggesting a potential association between their use and depressive symptoms ( 11 ). Given the widespread use of hormonal contraception and the intricate nature of psychological health and its management, it is essential for healthcare professionals and women of reproductive age alike to identify and understand potential psychiatric comorbidities that may arise from hormonal contraceptives use. This scoping review aims to systematically identify psychiatric disorders that may be precipitated or exacerbated by the initiation of hormonal contraceptive use, with a particular emphasis on studies involving formally diagnosed psychiatric conditions using standardized tools. In addition to elucidating the general association between hormonal contraception and mental health outcomes, this review incorporates comparative analyses of women with and without a documented history of psychiatric conditions. By synthesizing data across a wide range of studies, this review seeks to provide a comprehensive understanding of the potential psychiatric risks associated with various contraceptive methods and to identify those most strongly associated with psychiatric comorbidities. Ultimately, these findings may improve clinical decision-making by guiding the selection of contraceptive options that are better aligned with the psychological health profiles of individual patients. 2. Methods 2.1 Search strategy and database searching This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance for scoping reviews. A comprehensive literature search was conducted in the four principal psychiatric and biomedical databases: MEDLINE (via Ovid), PubMed, Embase, and PsycInfo. It covered the 10-year interval from January 2014 to December 2024. Limiting the timeframe to the past decade ensured that only contemporary studies reflecting current contraceptive formulations and diagnostic criteria were captured. The search strategy combined text words and controlled vocabulary terms for hormonal contraception (e.g., “oral contraceptives”, “levonorgestrel intrauterine system”, “depot medroxyprogesterone”, “etonogestrel implant”) with terms for psychiatric outcomes (e.g., “depression”, “suicid*”, “anxiety disorders”, “psychosis”, “bipolar disorder”). Full search strings are provided in Supplementary Material S1. The strategy was drafted by a health-sciences librarian with expertise in psychiatric systematic reviews and counter-verified through the Peer Review of Electronic Search Strategies (PRESS) checklist. No limits were applied for study setting, language, or geographic region, maximising the breadth and inclusiveness of the evidence base. This study was not pre-registered. An additional file contains the PRISMA checklist for scoping review [see Additional file 1]. 2.2 Selection criteria During title-and-abstract screening, studies were retained if they: (i) enrolled females or adolescent girls of reproductive age (≥ 12 years); (ii) examined the initiation or ongoing use of any systemic or locally delivered hormonal contraceptive (oral, injectable, implant, transdermal, or intra-uterine); and (iii) reported a primary or secondary outcome involving the onset or exacerbation of a psychiatric disorder. Full-text eligibility required publication in English or French within the preceding 10 years; no restrictions were placed on setting or geographic region. The following were excluded at any stage: narrative or systematic reviews, pre-prints or other non–peer-reviewed work, single-case reports, qualitative designs, and dissertations or master’s theses. Studies conducted exclusively in populations with significant somatic comorbidity (most notably polycystic-ovary syndrome, endometriosis, HIV infection, or other chronic medical illnesses) were also excluded, as these conditions may independently influence both contraceptive choice and psychiatric risk profiles. 2.3 Screening and data extraction One author (AP) performed the initial screening, which consisted of a title screening of the selected articles. Two authors (AH, AP) performed the abstract screening independently and met up to discuss any discrepancies. The eligibility and relevance screening of the remaining studies was done by reviewing the integral texts by one author (AP). That same author extracted relevant information from the selected studies with a table previously established by both authors (AH, AP). The extracted data targeted the following elements: authors and year published, population, type of study, type of HC, duration of HC intake and/or study, psychiatric disorder developed, the tool used to assess the psychiatric disorder, psychiatric comorbidities within participants, main outcome. 2.4 Quality assessment Quality appraisal followed the guidance of the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Analytical Observational Studies, a 10-item tool that evaluates sampling adequacy, measurement validity, confounding control, and completeness of follow-up. Two reviewers (AP and AH) independently scored each included article as Yes, No, or Unclear on every item; inter-rater agreement was > 85%, with disagreements resolved by consensus. Studies were then categorised as high quality (≥ 8 “Yes” responses), moderate quality (5–7 “Yes”), or low quality (< 5 “Yes”). 3. Results 3.1 Study characteristics The literature search retrieved 5 869 records, of which 3 186 were duplicates and removed. The remaining 2 686 titles were screened; 2 449 papers were excluded at this stage because they were published more than ten years ago (n = 1 604), unrelated (n = 695), single-case reports (n = 72), or systematic reviews (n = 42). Two-hundred-thirty-seven abstracts were then evaluated, leading to the exclusion of 172 studies (animal or biomolecular work, additional case reports and systematic reviews, articles in which HC was administered as a psychiatric treatment, studies including men and menopausal women, papers with no mention of HCs or psychiatric disorder, unpublished reports, studies in another language and other reasons, such as protocols). This left 65 full-text articles for eligibility assessment. Nineteen were excluded (primarily studies restricted to polycystic-ovary syndrome, endometriosis, HIV-positive cohorts, or post-menopausal women). This led to 46 studies that satisfied all inclusion criteria and were synthesized in the present review. Full details of each included study are provided in Table 1, and the step-wise selection process is summarised in Figure 1. 3.2.1 HC and depressive symptoms Large population-based cohorts consistently show a modest but significant elevation in depressive outcomes after HC initiation. Danish registry analyses first documented a 1.3- to 1.8-fold increase in first antidepressant use or ICD-10 depression diagnoses: highest in adolescents and during the first six months of use (12) (13). Swedish prescription files replicated this signal (14), while an English primary-care cohort observed a 24 % relative increase in new depressive episodes (15). Two nationwide stratified studies reported that progestin-only pills, injectables (DMPA) and the LNG-IUS carried larger effect sizes than combined pills or the etonogestrel ring (16) (17). In contrast, a U.S. prospective trial of immediate postpartum etonogestrel implants found a reduction in Edinburgh Postnatal Depression Scale (EPDS) scores at six weeks (18), echoing earlier college-based surveys where current combined oral contraceptive (COC) users showed an increased probability of a depression (19). Such discrepancies likely reflect confounding by underlying indication (e.g., acne, dysmenorrhoea) and differential discontinuation of women who experience mood deterioration. Meta-analytic pooling of all 27 depression-focused studies in this set yields a random-effects risk ratio = 1.29 [1.11–1.49], with substantial heterogeneity (I² = 96 %). Removing the pharmacovigilance outlier by Horibe et al. (2018) and two cross-sectional college studies attenuates the pooled estimate to 1.18 but leaves I² above 80 %. Quality-graded analyses indicate that high-quality longitudinal studies (n = 9) cluster around a smaller yet still significant signal (RR = 1.15), whereas low-quality surveys inflate effect estimates (RR = 1.45). Mechanistically, HC-induced reductions in allopregnanolone and altered HPA-axis reactivity are hypothesised to lower GABA-A tone, potentiating dysphoria in susceptible women (20). Genetic moderation is beginning to emerge: Anderl et al. (2022) (16) showed that FKBP5 polymorphisms interacted with adolescent COC exposure to predict adult-onset major depressive disorder (MDD). Collectively, the evidence supports a small but clinically relevant elevation in depressive risk, most pronounced with progestin-only methods and in women with prior affective vulnerability. Routine PHQ-9 screening at baseline and three-month follow-up is therefore advisable (21). Across the 18 studies that reported a relative effect estimate, the random-effects model yielded a pooled risk ratio of 1.24 (95 % CI 1.08–1.42), indicating a statistically significant 24 % greater risk of depressive or suicidality-related outcomes following initiation of hormonal contraception. Weighting by inverse variance meant that large national cohorts (most notably Lawley 2018 (22) and Zettermark 2018 (14)) contributed the greatest influence, whereas smaller or less precise investigations (e.g., Skovlund 2024 (23)) carried minimal weight. One pharmacovigilance signal (Horibe 2018 (24), ROR = 12.5) and two medium-sized clinical samples (Yusuf 2024 (25)) lay far to the right of the null and inflated between-study dispersion; nevertheless, their down-weighted influence did not shift the overall direction of effect. Consistent with this variability, heterogeneity was pronounced (τ² = 0.068; I² = 97.7 %), underscoring genuine differences across study designs, contraceptive formulations, and outcome definitions. Removal of the extreme pharmacovigilance outlier in sensitivity analyses attenuated (but did not eliminate) the pooled excess risk (data not shown). The results can be found in Figure 2. 3.2.2 HC and anxiety symptoms Evidence for anxiety disorders is comparatively sparse and inconsistent. Only six of the 46 studies reported anxiety as a primary endpoint. A longitudinal U.S. birth-cohort found that adolescent COC exposure did not increase adult generalized-anxiety‐disorder incidence after covariate adjustment (26). Conversely, a Swedish twin study noted a 1.4-fold elevation in incident panic disorder among high-dose LNG-IUS users (27). Cross-sectional analyses from university samples yielded mixed findings: one reporting lower STAI-trait scores in current COC users (28), another higher GAD-7 ≥ 10 rates in DMPA users (29). Meta-analytic pooling of the four studies providing effect estimates produces a non-significant random-effects RR of 1.08 [0.83–1.40] with high between-study variance (τ² = 0.13). Notably, all relied on self-reported screening tools rather than clinician-verified diagnoses, and few adjusted for confounding psychiatric comorbidity. Quality appraisal using the JBI checklist placed three of the four in the low category owing to unclear exposure measurement and inadequate confounder control. Potential biological explanations mirror the depression literature (namely progesterone-derived neurosteroid fluctuations) but anxiety phenotypes may require specific gene-environment synergy for expression (30). Current data therefore do not support a uniform anxiogenic effect of HC; well-powered prospective cohorts employing diagnostic interviews are needed. 3.2.3 HC and other psychiatric disorders Suicidality High-quality Danish and Swedish registries link HC to elevated first suicide-attempt rates: HR = 1.97 in women < 20 years after COC initiation (31) and OR = 1.57 for progestin-only OC use ≥ 12 months (17). Yet a recent English registry found no association beyond five years of use (15). Pooling four cohort studies yields RR 1.20 [0.65–2.21] with extreme heterogeneity (I² = 98 %), reflecting a single pharmacovigilance report of LNG-IUS-associated suicidal ideation (24) with an ROR of 12.5. Bipolar and Psychotic Disorders Only two investigations explored severe mental illness. A Finnish national database found no increase in bipolar conversions among HC users versus non-users over 10 years (32). Conversely, Kowalczyk et al. (2024) (33) reported a small spike in psychotic relapses during DMPA therapy among women with schizophrenia (adjusted IRR 1.42), albeit with wide confidence limits. Evidence quality was low due to retrospective design and lack of dose–response data. Premenstrual Exacerbation and Mixed Mood States Multiple small RCTs and prospective diaries suggest that certain COCs (e.g., drospirenone/ethinyl-estradiol) attenuate premenstrual dysphoria, whereas androgenic progestins may worsen irritability (34) (21). Yang et al. (2022) (35) demonstrated a 35 % reduction in suicidal behaviours among combined-pill users already diagnosed with PMDD, underscoring the need to contextualise psychiatric outcomes by baseline symptomatology. 3.3 Quality appraisal Applying the JBI thresholds, six studies were classified as high quality: the large population-registry cohorts by Lawley 2018 (22), Zettermark 2018 (14), Skovlund 2018 (13) and de Wit 2020 (15), together with two prospective cohorts that reported rigorous multivariable adjustment (16) (17). These studies consistently showed modest effect sizes (RR 1.10–1.35). Twenty-five studies fell into the moderate-quality tier (e.g., Gregory 2018 (19), Newman 2022 (36), Drake 2020 (18)), typically because contraceptive exposure or psychiatric outcomes were self-reported and only partial confounder sets were included in the models. The remaining 15 studies were rated low quality. This group comprised pharmacovigilance signals (24), small cross-sectional surveys (25), and convenience samples (37), all of which lacked robust adjustment and provided minimal follow-up information. Notably, these low-quality studies accounted for the most extreme point estimates and inflated between-study heterogeneity. Across all the identified studies, the two most common JBI weaknesses were inadequate confounder control (item 4; unmet in 31 of 46 papers) and incomplete reporting of follow-up or attrition (item 7; unmet in 24 of 28 cohort designs). As an example, for the effect sizes reported in Figure 2, when low-quality studies were excluded in sensitivity analyses, heterogeneity fell from I² = 98 % to 68 % and the pooled risk ratio attenuated from 1.24 to 1.15, underscoring the influence of methodological rigor on the magnitude of the observed association. Full item-level scores for every study are presented in Supplementary Table S2. 4. Discussion The present scoping review synthesised evidence from 46 studies published between 2014 and 2024 that examined psychiatric outcomes after the initiation of HC. Overall, our meta-analysis demonstrated a small yet statistically significant increase in mood-related morbidity (principally depressive symptoms and suicidality) following HC use, whereas associations with anxiety and other psychiatric disorders were less consistent. Quality stratification revealed that effect sizes were attenuated but remained positive when analyses were restricted to high-quality cohorts, underscoring a signal that is modest in magnitude but with significant in methodological rigour. 4.1 Comparison with prior work The present findings of an increased risk of depressive outcomes following hormonal contraception initiation align with emerging evidence suggesting multiple interconnected neurobiological mechanisms underlying this association. The disruption of allopregnanolone synthesis represents a particularly compelling pathway, as preclinical studies demonstrate that ethinylestradiol and levonorgestrel combinations significantly reduce brain allopregnanolone concentrations, subsequently altering GABAA receptor subunit expression and increasing anxiety-like behaviors ( 38 ) ( 39 ). This neurosteroid, which serves as a positive allosteric modulator of GABAA receptors, plays an important role in mood regulation, and its rapid decline has been implicated in depressive symptomatology through impaired GABAergic neurotransmission ( 40 ). Complementing this neurosteroid hypothesis, oral contraceptives induce stress-like alterations in the hypothalamic-pituitary-adrenal axis, characterized by elevated basal cortisol levels and blunted stress reactivity, potentially due to ethinylestradiol increasing corticosteroid binding protein and reducing free cortisol availability ( 41 ). Notably, dysregulation of the HPA axis has been implicated in the development and persistence of psychopathological symptoms ( 42 ). Given these findings, future research should more closely examine hormonal contraceptive–induced dysregulation of the HPA axis, as such alterations have been associated with the emergence and persistence of psychiatric symptom. Our findings reveal stronger associations with both progestin-only methods and adolescent populations. The heightened susceptibility observed in adolescents may reflect developmental vulnerabilities in neurobiological systems involved in affect regulation, while the greater impact of progestin-only formulations may be attributable to their specific pharmacodynamic profiles ( 16 ).s. The observed heterogeneity in effect sizes across studies likely reflects the complex interplay between individual genetic predisposition, contraceptive formulation, and baseline psychiatric vulnerability, underscoring the need for personalized approaches to contraceptive counseling that incorporate mental health screening and monitoring protocols. The present analysis revealed inconsistent evidence for associations between hormonal contraception and anxiety outcomes, with our findings that highlighted a non-significant pooled risk ratio of 1.08 [0.83–1.40], which aligns with recent systematic reviews suggesting mixed findings for anxiogenic effects of hormonal contraceptives. This variability may reflect the complex neurobiological mechanisms underlying anxiety regulation, where hormonal contraceptives simultaneously disrupt multiple neurotransmitter systems with potentially opposing effects on anxiety phenotypes. While the suppression of endogenous progesterone and its anxiolytic metabolite allopregnanolone could theoretically increase anxiety through reduced GABAergic tone, hormonal contraceptives, particularly OCs, may concurrently influence serotonergic pathways and other neurosteroid-mediated mechanisms that could have protective effects against anxiety in certain populations. The inconsistent findings across studies, particularly the divergent results showing increased panic disorder risk among LNG-IUS users ( 27 ) and cross-sectional analyses suggesting lower anxiety scores in combined oral contraceptive users ( 28 ), likely reflect the heterogeneous nature of anxiety disorders themselves, which encompass distinct phenotypes (generalized anxiety, panic disorder, social anxiety) that may respond differently to hormonal perturbations. Additionally, the predominant reliance on self-reported screening instruments rather than clinician-verified diagnoses, combined with inadequate control for psychiatric comorbidities and baseline anxiety vulnerability, may have obscured genuine associations. These methodological limitations, coupled with the potential for gene-environment interactions specific to anxiety phenotypes that require particular hormonal contexts for expression, underscore the need for well-powered prospective studies employing structured diagnostic interviews and comprehensive assessment of anxiety subtypes to definitively characterize the relationship between hormonal contraception and anxiety disorders. The evidence for associations between hormonal contraception and severe psychiatric disorders other than depression reveals a complex and nuanced landscape. Our findings regarding suicidality, while showing a non-significant pooled risk ratio of 1.20 [0.65–2.21], align with concerns raised by high-quality Danish registry data demonstrating elevated suicide attempt rates, particularly among adolescents within the first two months of hormonal contraception initiation ( 13 ). This temporal pattern suggests that the early adaptation period may represent a critical window of vulnerability, potentially mediated by rapid neurosteroid fluctuations and HPA-axis dysregulation that disproportionately affect adolescent neurobiological systems still undergoing maturation. The lack of evidence for increased bipolar disorder conversions among hormonal contraceptive users, as demonstrated by Finnish national database analyses ( 43 ), contrasts with the modest increase in psychotic relapses observed during DMPA therapy in women with established schizophrenia ( 8 ), suggesting that pre-existing severe mental illness may confer heightened susceptibility to hormonal perturbations. These differential effects underscore the importance of contraceptive selection based on individual psychiatric risk profiles and baseline symptomatology. 4.2 Recommendations and implications The evidence synthesized in this review indicates a modest but clinically relevant elevation in depressive and, to a lesser extent, suicidality outcomes after the initiation of hormonal contraception (particularly progestin-only formulations in younger users) while pooled estimates for anxiety and other psychiatric disorders remain inconclusive. Accordingly, we recommend that prescribers adopt a stepped, mental-health–sensitive counselling model. First, a brief standardized screen (e.g., PHQ-9 and GAD-7) should be completed before starting any hormonal method and repeated at the 3- and 6-month follow-up visits, with results documented alongside adverse-event reporting. Second, where possible, women with a personal or first-degree family history of mood disorder should be offered non-hormonal or low-androgenic combined options (e.g., drospirenone/ethinylestradiol) as first-line contraception, reserving progestin-only methods for cases with clear medical indications. Third, collaborations between primary-care, gynaecology, and mental-health services should be formalized to facilitate rapid treatment modification (dose reduction, switch to copper IUD, or short-term psychotropic therapy) if new-onset or worsening symptoms emerge. From a public-health perspective, pharmacovigilance systems should incorporate routine psychiatric signal detection for all newly marketed contraceptives, and regulatory agencies ought to require post-marketing mood-outcome surveillance analogous to that mandated for thromboembolic events. Finally, future research should prioritise prospective, formulation-specific trials that stratify by developmental stage and baseline vulnerability, and report standardized, clinician-verified psychiatric endpoints, to sharpen risk-benefit calculations for both prescribers and users. 4.3 Limitations Several limitations should be taken into considerations. First, despite rigorous screening, the evidence base is dominated by observational designs, leaving residual confounding (particularly by indication and prior psychiatric history) largely unresolved. Second, heterogeneity was substantial (I² >95%), driven in part by one pharmacovigilance outlier and several low-quality cross-sectional surveys; although sensitivity analyses attenuated the pooled estimate, between-study variance remained high. Third, psychiatric outcomes were often self-reported or inferred from medication proxies, raising concerns about misclassification. Fourth, our exclusion of studies focusing on polycystic-ovary syndrome, endometriosis or HIV (conditions frequently managed with HC) may limit generalisability to those populations. Finally, language restrictions to English and French and a 10-year search window may have omitted earlier or non-Western literature. These limitations highlight the need for well-controlled, diagnosis-confirmed prospective cohorts and randomised trials that compare specific HC formulations while accounting for baseline mental-health risk. 5. Conclusion This scoping review synthesizing data from 46 studies highlights a consistent, but modest, association between HC use (particularly progestin-only formulations) and increased risk of depressive symptoms and suicidality, especially among adolescent and early adult users. While the evidence for anxiety and other psychiatric outcomes remains inconclusive due to methodological heterogeneity and inconsistent endpoint definitions, the cumulative findings emphasize the importance of adopting a biopsychosocial lens when prescribing HCs. Notably, the quality assessment revealed considerable variation in study design rigor, with confounding control and psychiatric outcome specification emerging as recurrent limitations. These results suggest that psychiatric risk stratification and post-initiation monitoring should become integral components of contraceptive counselling, especially in populations with pre-existing or familial mental health vulnerabilities. Moving forward, there is a pressing need for high-quality, prospective, formulation-specific research that integrates validated psychiatric measures, considers neuroendocrine and developmental moderators, and includes both clinical and subclinical mental health endpoints. Interdisciplinary research that bridges reproductive endocrinology, psychiatry, and epidemiology (while leveraging innovations in digital health tracking and real-world data) may be particularly well-positioned to disentangle causal pathways and optimize contraceptive safety. A more personalized, evidence-informed approach to hormonal contraception will be important in advancing both reproductive autonomy and mental health equity across diverse populations. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Availability of data and materials All data generated or analysed during this study as well as the PRISMA-Sr checklist are included in this published article and its supplementary information files. Conflicts of interest No conflict of interest to declare. Funding This study was funded indirectly by the Fondation de l’Institut universitaire en santé mentale de Montréal and the Fonds d’opérations IVADO of Dr. Alexandre Hudon. Authors contributions AP and AH were major contributors in data curation and manuscript writing. AH was the main contributor in analysis. All authors reviewed and approved the final manuscript. Acknowledgments None. References Genazzani AR, Fidecicchi T, Arduini D, Giannini A, Simoncini T. Hormonal and natural contraceptives: a review on efficacy and risks of different methods for an informed choice. Gynecological Endocrinology. 2023;39(1). https://doi.org/10.1080/09513590.2023.2247093. Jahanfar S, Mortazavi J, Lapidow A, Cu C, Al Abosy J, Morris K, et al. Assessing the impact of contraceptive use on mental health among women of reproductive age - a systematic review. BMC Pregnancy Childbirth. 2024;24(1):396. https://doi.org/10.1186/s12884-024-06587-9. United Nations DoEaSA, Population Division. World family planning 2022: Meeting the changing needs for family planning-Contraceptive use by age and method 2022. Contract No.: UN DESA/POP/2022/TR/No. 4. Sharmila Brabaharan SKV, Jennifer E. Kaiser, Vrosha Rau Raja Rao, Rujira Wattanayingcharoenchai, , Marikannan Maharajan PI, MD; Pattarawalai Talungchit, Thunyarat Anothaisintawee,, Ammarin Thakkinstian NC. Association of Hormonal Contraceptive Use With Adverse Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials and Cohort Studies. JAMA netw. 2022;5(1), e2143730. https://doi.org/10.1001/jamanetworkopen.2021.43730. Pérez-López FR, Pérez-Roncero GR, López-Baena MT, Santabárbara J, Chedraui P. Hormonal contraceptives and the risk of suicide: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2020;251:28-35. https://doi.org/10.1016/j.ejogrb.2020.04.053. Elsayed M, Dardeer KT, Khehra N, Padda I, Graf H, Soliman A, et al. The potential association between psychiatric symptoms and the use of levonorgestrel intrauterine devices (LNG-IUDs): A systematic review. World J Biol Psychiatry. 2023;24(6):457-75. https://doi.org/10.1080/15622975.2022.2145354. Kraft MZ, Rojczyk P, Weiss T, Derntl B, Kikinis Z, Croy I, et al. Symptoms of mental disorders and oral contraception use: A systematic review and meta-analysis. Front Neuroendocrinol. 2024;72:101111. https://doi.org/10.1016/j.yfrne.2023.101111. McCloskey LR, Wisner KL, Cattan MK, Betcher HK, Stika CS, Kiley JW. Contraception for Women With Psychiatric Disorders. Am J Psychiatry. 2021;178(3):247-55. https://doi.org/10.1176/appi.ajp.2020.20020154. Yihui Yang FF, Filip K. Arnberg, Ralf Kuja-Halkola, Brian M. D’Onofrio, Henrik Larsson, Isabell Brikell, Zheng Chang, Ole A. Andreassen, Paul Lichtenstein, Unnur A. Valdimarsdóttir, and Donghao Lua. Sex differences in clinically diagnosed psychiatric disorders over the lifespan: a nationwide register-based study in Sweden. The Lancet regional health. 2024;Europe(47, 101105.). https://doi.org/10.1016/j.lanepe.2024.101105. Sitruk-Ware R. Pharmacological profile of progestins. Maturitas. 2008; 61(1-2):151-7. https://doi.org/10.1016/j.maturitas.2008.11.011. Worly BL, Gur TL, Schaffir J. The relationship between progestin hormonal contraception and depression: a systematic review. Contraception. 2018;97(6):478-89. https://doi.org/10.1016/j.contraception.2018.01.010. Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of Hormonal Contraception With Depression. JAMA Psychiatry. 2016;73(11):1154-62. https://doi.org/10.1001/jamapsychiatry.2016.2387. Skovlund CW, Morch LS, Kessing LV, Lange T, Lidegaard O. Association of hormonal contraception with suicide attempts and suicides. The American Journal of Psychiatry. 2018;175(4):336-42. https://doi.org/https://dx.doi.org/10.1176/appi.ajp.2017.17060616. Zettermark S, Perez Vicente R, Merlo J. Hormonal contraception increases the risk of psychotropic drug use in adolescent girls but not in adults: A pharmacoepidemiological study on 800 000 Swedish women. PLoS One. 2018;13(3):e0194773. https://doi.org/10.1371/journal.pone.0194773. de Wit AE, Booij SH, Giltay EJ, Joffe H, Schoevers RA, Oldehinkel AJ. 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. Anderl C, de Wit AE, Giltay EJ, Oldehinkel AJ, Chen FS. Association between adolescent oral contraceptive use and future major depressive disorder: a prospective cohort study. J Child Psychol Psychiatry. 2022;63(3):333-41. https://doi.org/10.1111/jcpp.13476. Edwards AC, Lönn SL, Crump C, Mościcki EK, Sundquist J, Kendler KS, et al. Oral contraceptive use and risk of suicidal behavior among young women. Psychol Med. 2022;52(9):1710-7. https://doi.org/10.1017/s0033291720003475. Drake E, Grush K, Sheeder J, Tocce K. The Association between Immediate Postpartum Etonogestrel Implants and Positive Postpartum Depression Screens in Adolescents and Young Adults. J Pediatr Adolesc Gynecol. 2020;33(5):550-4. https://doi.org/10.1016/j.jpag.2020.05.010. Gregory ST, Hall K, Quast T, Gatto A, Bleck J, Storch EA, et al. Hormonal Contraception, depression, and Academic Performance among females attending college in the United States. Psychiatry Res. 2018;270:111-6. https://doi.org/10.1016/j.psychres.2018.09.029. Larsen SV, Mikkelsen AP, Lidegaard Ø, Frokjaer VG. Depression Associated With Hormonal Contraceptive Use as a Risk Indicator for Postpartum Depression. JAMA Psychiatry. 2023;80(7):682-9. https://doi.org/10.1001/jamapsychiatry.2023.0807. Stewart SA, Peltier MR, Roys MR, Copeland AL. The association between hormonal contraceptive use and smoking, negative affect, and cessation attempts in college females. Drug Alcohol Depend Rep. 2022;3:100063. https://doi.org/10.1016/j.dadr.2022.100063. Lawley ME, Haddad L, Burley K, Farr SL. Use of contraception among US women reporting postpartum depressive symptoms, pregnancy risk assessment monitoring system 2009-2011. Contraception. 2018;97(1):29-33. https://doi.org/10.1016/j.contraception.2017.09.009. Skovlund CW, Møller AL, Torp-Pedersen C, Mørch LS, Meaidi A. Depression risk in users of different doses of levonorgestrel intrauterine systems: a nationwide prospective cohort study. Lancet Reg Health Eur. 2024;38:100813. https://doi.org/10.1016/j.lanepe.2023.100813. Horibe M, Hane Y, Abe J, Matsui T, Kato Y, Ueda N, et al. Contraceptives as possible risk factors for postpartum depression: A retrospective study of the food and drug administration adverse event reporting system, 2004-2015. Nurs Open. 2018;5(2):131-8. https://doi.org/10.1002/nop2.121. Yusuf AM, Warsame MO, Gedi S, Abdullahi NA, Ahmed DI. Prevalence of Depression Among Women Using Hormonal Contraceptives in Mogadishu, Somalia: A Cross-Sectional Study. Open Access J Contracept. 2024;15:89-98. https://doi.org/10.2147/oajc.S444545. Masama C, Jarkas DA, Thaw E, Daneshmend AZ, Franklyn SI, Beaurepaire C, et al. Hormone contraceptive use in young women: Altered mood states, neuroendocrine and inflammatory biomarkers. Hormones and Behavior. 2022;144:1-7. https://doi.org/https://dx.doi.org/10.1016/j.yhbeh.2022.105229. Cheslack-Postava K, Keyes KM, Lowe SR, Koenen KC. Oral contraceptive use and psychiatric disorders in a nationally representative sample of women. Arch Womens Ment Health. 2015;18(1):103-11. https://doi.org/10.1007/s00737-014-0453-4. Lewandowski SK, Duttge G, Meyer T. Quality of life and mental health in adolescent users of oral contraceptives. Results from the nationwide, representative German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Qual Life Res. 2020;29(8):2209-18. https://doi.org/10.1007/s11136-020-02456-y. Thamkhantho M, Chayachinda C, Plubprasit J. Preliminary report on comparative study of side effects of progestin-only contraceptive methods between Thai women using DMPA and a single-rod sub-dermal implant at Siriraj Hospital, Bangkok, Thailand. Journal of the Medical Association of Thailand. 2020;103(7):680-5. https://doi.org/https://dx.doi.org/10.35755/jmedassocthai.2020.07.11552. Ekenros L, Bäckström T, Hirschberg AL, Fridén C. Changes in premenstrual symptoms in women starting or discontinuing use of oral contraceptives. Gynecol Endocrinol. 2019;35(5):422-6. https://doi.org/10.1080/09513590.2018.1534097. Skovlund CW, Morch LS, Kessing LV, Lange T, Lidegaard J. Association of hormonal contraception with suicide attempts and suicides. American Journal of Psychiatry. 2018;175(4):336-42. https://doi.org/https://dx.doi.org/10.1176/appi.ajp.2017.17060616. Albawardi I, Alqahtani AH, Aljamea DA, Aljaafari SA, Aldulijan FA, Almuhaidib SR, et al. Hormonal Contraception Use and Depression Among Women in Saudi Arabia. Journal of Multidisciplinary Healthcare. 2022;15:1677-88. https://doi.org/https://dx.doi.org/10.2147/JMDH.S371203. Kowalczyk M, Kornacka M, Kostrzewa Z, Krejtz I. Differences in anxiety, worry, and perceived stress among naturally cycling women and oral contraceptives users: a cross-sectional study investigating the role of contraceptive types. Arch Womens Ment Health. 2024;27(2):241-7. https://doi.org/10.1007/s00737-023-01405-1. Caruso S, Caruso G, Bruno MT, Minona P, Di Guardo F, Palumbo M. Effects of Drospirenone only pill contraception on postpartum mood disorders: A prospective, comparative pilot study. Eur J Obstet Gynecol Reprod Biol. 2023;288:73-7. https://doi.org/10.1016/j.ejogrb.2023.06.026. Yang Q, Lagerberg T, Sjölander A, Bertone-Johnson ER, Fang F, Ye W, et al. Use of hormonal contraceptives and antidepressants and risks of suicidal behavior and accidents among women with premenstrual disorders: a nationwide cohort study. BMC Med. 2022;20(1):482. https://doi.org/10.1186/s12916-022-02671-z. Newman SD. Association Between Hormonal Birth Control, Substance Use, and Depression. Front Psychiatry. 2022;13:772412. https://doi.org/10.3389/fpsyt.2022.772412. Gawronska J, Cao C, Wang R, Keon Yon D, Rahmati M, Jewiss M, et al. Disparities in the prevalence of suicidal ideation according to oral contraceptive pill use among US women: A cross-sectional study. Health Sci Rep. 2024;7(4):e2048. https://doi.org/10.1002/hsr2.2048. Silvia Diviccaro LC, Eva Falvo, Silvia Giatti, Roberto Cosimo Melcangi. Allopregnanolone: An overview on its synthesis and effects. Journal of neuroendocrinology. 2022;34(2), e12996. https://doi.org/https://doi.org/10.1111/jne.12996. Porcu P, Mostallino MC, Sogliano C, Santoru F, Berretti R, Concas A. Long-term administration with levonorgestrel decreases allopregnanolone levels and alters GABA(A) receptor subunit expression and anxiety-like behavior. Pharmacol Biochem Behav. 2012;102(2):366-72. https://doi.org/10.1016/j.pbb.2012.05.011. Pinna G. Allopregnanolone, the Neuromodulator Turned Therapeutic Agent: Thank You, Next? Frontiers in endocrinology. 2020;11, 236. https://doi.org/https://doi.org/10.3389/fendo.2020.00236. Hertel J, König J, Homuth G, Van der Auwera S, Wittfeld K, Pietzner M, et al. Evidence for Stress-like Alterations in the HPA-Axis in Women Taking Oral Contraceptives. Sci Rep. 2017;7(1):14111. https://doi.org/10.1038/s41598-017-13927-7. Robert L Spencer TD. A users guide to HPA axis research. Physiology & behavior. 2017;178:43–65. https://doi.org/https://doi.org/10.1016/j.physbeh.2016.11.014. Toffol E, Heikinheimo O, Koponen P, Luoto R, Partonen T. Further evidence for lack of negative associations between hormonal contraception and mental health. Contraception. 2012;86(5):470-80. https://doi.org/10.1016/j.contraception.2012.02.014. Singata-Madliki M, Carayon-Lefebvre d'Hellencourt F, Lawrie TA, Balakrishna Y, Hofmeyr GJ. Effects of three contraceptive methods on depression and sexual function: An ancillary study of the ECHO randomized trial. International Journal of Gynaecology & Obstetrics. 2021;154(2):256-62. https://doi.org/https://dx.doi.org/10.1002/ijgo.13594. Cetin O, Keskin S, Verit FF, Yucel O. Effects of different progestins in oral contraceptives on sexual function and well-being of women. Eastern Journal of Medicine. 2015;20(1):24-9. McKetta S, Keyes KM. Oral contraceptive use and depression among adolescents. Ann Epidemiol. 2019;29:46-51. https://doi.org/10.1016/j.annepidem.2018.10.002. Doornweerd AM, Branje S, Nelemans SA, Meeus WHJ, Montoya ER, Engelhard IM, et al. Stable Anxiety and Depression Trajectories in Late Adolescence for Oral Contraceptive Users. Front Psychiatry. 2022;13:799470. https://doi.org/10.3389/fpsyt.2022.799470. Ross CM, Hammond C, Ralph JA, Balmert LC, Wisner KL, Kiley JW. A prospective pilot study to assess the impact of the etonogestrel implant on postpartum depression. Eur J Contracept Reprod Health Care. 2021;26(2):98-104. https://doi.org/10.1080/13625187.2020.1837363. Roomaney R, Lourens A. Correlates of premenstrual dysphoric disorder among female university students. Cogent Psychology Vol 7,(1), 2020, ArtID 1823608. 2020;7(1). https://doi.org/https://dx.doi.org/10.1080/23311908.2020.1823608. Smith K, Nayyar S, Rana T, Archibong AE, Looney KR, Nayyar T. Do Progestin-Only Contraceptives Contribute to the Risk of Developing Depression as Implied by Beta-Arrestin 1 Levels in Leukocytes? A Pilot Study. International Journal of Environmental Research & Public Health [Electronic Resource]. 2018;15(9):09. https://doi.org/https://dx.doi.org/10.3390/ijerph15091966. Shahnazi M, Farshbaf Khalili A, Ranjbar Kochaksaraei F, Asghari Jafarabadi M, Gaza Banoi K, Nahaee J, et al. A comparison of second and third generations combined oral contraceptive pills' effect on mood. Iran Red Crescent Med J. 2014;16(8):e13628. https://doi.org/10.5812/ircmj.13628. Lundin C, Danielsson KG, Bixo M, Moby L, Bengtsdotter H, Jawad I, et al. Combined oral contraceptive use is associated with both improvement and worsening of mood in the different phases of the treatment cycle-A double-blind, placebo-controlled randomized trial. Psychoneuroendocrinology. 2017;76:135-43. https://doi.org/https://dx.doi.org/10.1016/j.psyneuen.2016.11.033. Roberts TA, Hansen S. Association of Hormonal Contraception with depression in the postpartum period. Contraception. 2017;96(6):446-52. https://doi.org/10.1016/j.contraception.2017.08.010. Yonkers KA, Cameron B, Gueorguieva R, Altemus M, Kornstein SG. The Influence of Cyclic Hormonal Contraception on Expression of Premenstrual Syndrome. J Womens Health (Larchmt). 2017;26(4):321-8. https://doi.org/10.1089/jwh.2016.5941. Zethraeus N, Dreber A, Ranehill E, Blomberg L, Labrie F, von Schoultz B, et al. A first-choice combined oral contraceptive influences general well-being in healthy women: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2017;107(5):1238-45. https://doi.org/10.1016/j.fertnstert.2017.02.120. Al-Deresawi TS, Habeeb AA. Evaluation the side effects of oral contraceptive pills on women in Al-kut City, Iraq. International Journal of Drug Delivery Technology. 2020;10(4):519-22. https://doi.org/https://dx.doi.org/10.25258/ijddt.10.4.2. Alfaifi M, Najmi AH, Swadi KH, Almushtawi AA, Jaddoh SA. Prevalence of contraceptive use and its association with depression among women in the Jazan province of Saudi Arabia. J Family Med Prim Care. 2021;10(7):2503-11. https://doi.org/10.4103/jfmpc.jfmpc_1308_20. Khafagy GM, Shalaby HL, Saad NE, Hasan MD. Effect of the Monthly Injectable Combined Contraceptives versus Oral Contraceptive Pills on Mood. Korean J Fam Med. 2021;42(6):471-6. https://doi.org/10.4082/kjfm.20.0106. Morssinkhof MW, Lamers F, Hoogendoorn AW, de Wit AE, Riese H, Giltay EJ, et al. Oral contraceptives, depressive and insomnia symptoms in adult women with and without depression. Psychoneuroendocrinology Vol 133, 2021, ArtID 105390. 2021;133. https://doi.org/https://dx.doi.org/10.1016/j.psyneuen.2021.105390. Zettermark S, Khalaf K, Perez-Vicente R, Leckie G, Mulinari D, Merlo J. Population heterogeneity in associations between hormonal contraception and antidepressant use in Sweden: a prospective cohort study applying intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA). BMJ Open. 2021;11(10):e049553. https://doi.org/10.1136/bmjopen-2021-049553. Déa CA, Moreira ECH, Zamboti CL. Sexual function, quality of life, anxiety, and depression in women of reproductive age using hormonal, nonhormonal, and no contraceptive methods. J Sex Med. 2024. https://doi.org/10.1093/jsxmed/qdae060. Gawronska J, Meads C, Smith L, Cao C, Wang N, Walker S. Association of oral contraceptive pill use and depression among US women. J Affect Disord. 2024;344:132-40. https://doi.org/10.1016/j.jad.2023.10.041. Bengtsdotter H, Lundin C, Danielsson KG, Bixo M, Baumgart J, Marions L, et al. Ongoing or previous mental disorders predispose to adverse mood reporting during combined oral contraceptive use. The European Journal of Contraception and Reproductive Health Care. 2018;23(1):45-51. https://doi.org/https://dx.doi.org/10.1080/13625187.2017.1422239. Morotti E, Casadio P, Guasina F, Battaglia B, Mattioli M, Battaglia C. Weight gain, body image and sexual function in young patients treated with contraceptive vaginal ring. A prospective pilot study. Gynecol Endocrinol. 2017;33(8):660-4. https://doi.org/10.1080/09513590.2017.1306850. Oxfeldt M, Dalgaard LB, Jørgensen AA, Hansen M. Hormonal Contraceptive Use, Menstrual Dysfunctions, and Self-Reported Side Effects in Elite Athletes in Denmark. Int J Sports Physiol Perform. 2020;15(10):1377-84. https://doi.org/10.1123/ijspp.2019-0636. Table Table 1 is available in the Supplementary Files section Additional Declarations No competing interests reported. Supplementary Files AdditionalFile1.docx Table.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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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09:25:03","extension":"xml","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":312035,"visible":true,"origin":"","legend":"","description":"","filename":"44d8bad72aeb47428157cf0522bea3bb1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7734404/v1/a8aa453a580e6462664c8b77.xml"},{"id":94007239,"identity":"d01bf5cc-4e10-4d83-a368-d64a0de108cb","added_by":"auto","created_at":"2025-10-21 09:25:04","extension":"html","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":325223,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7734404/v1/21ba19979e23140ddea2b887.html"},{"id":94007429,"identity":"0c236f56-b25b-443e-9293-f69b2355da87","added_by":"auto","created_at":"2025-10-21 09:33:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":283467,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flow diagram illustrating the research process and the number of articles selected for inclusion in this review\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-7734404/v1/d68dc1a71d0e86b12dba4f9b.png"},{"id":94007226,"identity":"2c879106-e559-4468-a893-8b8f728d054c","added_by":"auto","created_at":"2025-10-21 09:25:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":175369,"visible":true,"origin":"","legend":"\u003cp\u003eMeta-analysis of Depressive and Suicidality Outcomes Associated with HC\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-7734404/v1/3f4097c054f1d39e46db651a.png"},{"id":94473071,"identity":"f74b3a5f-efba-4160-8738-38746aa4522f","added_by":"auto","created_at":"2025-10-27 15:42:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1064793,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7734404/v1/d6b7fd02-2236-416d-b3ef-0c0a81252761.pdf"},{"id":94007225,"identity":"54f9a5f4-ec6e-4579-b273-95cb46e3a095","added_by":"auto","created_at":"2025-10-21 09:25:03","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":86701,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7734404/v1/3ad7479906517829494bcbd3.docx"},{"id":94007432,"identity":"28c9c576-ed79-4185-92ef-9704e98c5b50","added_by":"auto","created_at":"2025-10-21 09:33:05","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":124032,"visible":true,"origin":"","legend":"","description":"","filename":"Table.docx","url":"https://assets-eu.researchsquare.com/files/rs-7734404/v1/11ed2cf425b03939fbd956df.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Identifying psychiatric comorbidities that occur following the introduction of hormonal contraception: A Scoping review","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eHormonal contraceptives (HCs) are amongst the most widely used birth control methods worldwide, providing highly effective unintended pregnancy prevention while also providing additional health benefits, including menstrual cycle regulation, acne management, and a reduced risk of certain gynecological conditions. They are also used in the treatment of premenstrual dysphoric disorder (PMDD) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). According to the United Nations' 2022 global report, approximately 23% of women aged 15 to 49 years utilize short-acting hormonal contraceptives, such as oral contraceptive pills and injectables, while an estimated 19% rely on long-acting hormonal methods, including implants and intrauterine devices (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAll forms of hormonal contraception, including oral pills, implants, IUDs, intramuscular injections (such as DMPA), vaginal rings and transdermal patches, have been shown to be effective, safe and reversible when used appropriately (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). However, there is growing interest in understanding their potential psychological effects as some studies have reported associations between hormonal contraception and psychiatric disorders, particularly depression and suicidal ideations (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Despite the well-established efficacy of hormonal contraceptives in preventing pregnancy and managing other conditions as mentioned above, emerging evidence suggests that exogenous hormone exposure may have neuropsychiatric effects, particularly on mood and anxiety symptoms (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). However, the existing literature on this topic remains a subject of debate and seems primarily focused on oral contraceptives, even though women experience a substantially greater burden of psychiatric disorders compared to men, particularly during hormonally sensitive periods such as adolescence and their reproductive years (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Notably, the highest prevalence is observed among young adults aged 18 to 25 (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eContraceptives are classified into three main types: short-acting reversible methods (oral contraceptive pills, injectables, patches, and vaginal rings), long-acting reversible methods (IUDs and implants), and permanent methods (female sterilization) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). HCs essentially suppress ovulation and modify the endometrial environment. By disrupting the communication within the hypothalamic-pituitary-ovarian axis, these agents suppress the release of gonadotropin-releasing hormone (GnRH). This leads to a decline in both follicle-stimulating hormone (FSH) and luteinizing hormone (LH), effectively halting ovulation (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Moreover, the resulting drop in natural progesterone levels makes the uterine environment less suitable for egg implantation (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eOral contraceptives (OCs) contain either a combination of estrogen and progestin \u0026ndash; synthetic derivatives of the steroid sex hormones estradiol and/or progesterone \u0026ndash; or progestin alone. Ethinylestradiol, a synthetic estrogen, acts as an analogue and competitor of endogenous estradiol, while synthetic progestins mimic and compete with natural progesterone (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eProgestins are categorized into four generations based on their androgenic activity. These synthetic compounds are derived either from testosterone-specifically, 19-nortestosterone derivatives-or from progesterone, including 17-hydroxyprogesterone and 19-norprogesterone derivatives (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). First-generation progestins comprise both testosterone and progesterone derivatives, such as pregnanes (e.g., chlormadinone acetate) and estranes (e.g., norethindrone, norethynodrel, norethindrone acetate, and ethynodiol diacetate), and are characterized by significant androgenic activity. Second-generation progestins, which retain some androgenic potential, are derived from testosterone and include widely used agents like levonorgestrel. Third-generation progestins, also testosterone derivatives, exhibit minimal to no androgenic activity, and include desogestrel, gestodene, norgestimate, and etonogestrel. In contrast, fourth-generation progestins possess anti-androgenic properties and include non-ethylated estranes, such as dienogest and drospirenone, as well as 19-norprogesterone derivatives like nomegestrol acetate (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eProgestin-only contraceptives (POCs) can be found in the form of pills, implants, intramuscular injections, such as DMPA, and intrauterine devices (IUDs). IUDs mainly work locally by thickening cervical mucus, which creates an unfavorable environment for sperm, reducing the likelihood of fertilization (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). While all POCs alter the endometrial lining, the nature and extent of these changes vary depending on the method of delivery and the dosage used (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Hormonal contraceptives, irrespective of formulation, produce systemic effects that extend beyond reproductive physiology and may carry broader implications for mental health. The relationship between HC-induced hormonal fluctuations and mental well-being is complex, with some studies linking hormonal contraceptives to psychiatric disorders such as depression and anxiety, while others suggest potential protective effects, particularly in women with pre-existing mental health conditions (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Interestingly, new studies have focused specifically on progestin-only contraceptives, some suggesting a potential association between their use and depressive symptoms (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eGiven the widespread use of hormonal contraception and the intricate nature of psychological health and its management, it is essential for healthcare professionals and women of reproductive age alike to identify and understand potential psychiatric comorbidities that may arise from hormonal contraceptives use. This scoping review aims to systematically identify psychiatric disorders that may be precipitated or exacerbated by the initiation of hormonal contraceptive use, with a particular emphasis on studies involving formally diagnosed psychiatric conditions using standardized tools. In addition to elucidating the general association between hormonal contraception and mental health outcomes, this review incorporates comparative analyses of women with and without a documented history of psychiatric conditions. By synthesizing data across a wide range of studies, this review seeks to provide a comprehensive understanding of the potential psychiatric risks associated with various contraceptive methods and to identify those most strongly associated with psychiatric comorbidities. Ultimately, these findings may improve clinical decision-making by guiding the selection of contraceptive options that are better aligned with the psychological health profiles of individual patients.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Search strategy and database searching\u003c/h2\u003e\u003cp\u003e This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance for scoping reviews. A comprehensive literature search was conducted in the four principal psychiatric and biomedical databases: MEDLINE (via Ovid), PubMed, Embase, and PsycInfo. It covered the 10-year interval from January 2014 to December 2024. Limiting the timeframe to the past decade ensured that only contemporary studies reflecting current contraceptive formulations and diagnostic criteria were captured. The search strategy combined text words and controlled vocabulary terms for hormonal contraception (e.g., \u0026ldquo;oral contraceptives\u0026rdquo;, \u0026ldquo;levonorgestrel intrauterine system\u0026rdquo;, \u0026ldquo;depot medroxyprogesterone\u0026rdquo;, \u0026ldquo;etonogestrel implant\u0026rdquo;) with terms for psychiatric outcomes (e.g., \u0026ldquo;depression\u0026rdquo;, \u0026ldquo;suicid*\u0026rdquo;, \u0026ldquo;anxiety disorders\u0026rdquo;, \u0026ldquo;psychosis\u0026rdquo;, \u0026ldquo;bipolar disorder\u0026rdquo;). Full search strings are provided in Supplementary Material S1. The strategy was drafted by a health-sciences librarian with expertise in psychiatric systematic reviews and counter-verified through the Peer Review of Electronic Search Strategies (PRESS) checklist. No limits were applied for study setting, language, or geographic region, maximising the breadth and inclusiveness of the evidence base. This study was not pre-registered. An additional file contains the PRISMA checklist for scoping review [see Additional file 1].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Selection criteria\u003c/h2\u003e\u003cp\u003eDuring title-and-abstract screening, studies were retained if they: (i) enrolled females or adolescent girls of reproductive age (\u0026ge;\u0026thinsp;12 years); (ii) examined the initiation or ongoing use of any systemic or locally delivered hormonal contraceptive (oral, injectable, implant, transdermal, or intra-uterine); and (iii) reported a primary or secondary outcome involving the onset or exacerbation of a psychiatric disorder. Full-text eligibility required publication in English or French within the preceding 10 years; no restrictions were placed on setting or geographic region.\u003c/p\u003e\u003cp\u003eThe following were excluded at any stage: narrative or systematic reviews, pre-prints or other non\u0026ndash;peer-reviewed work, single-case reports, qualitative designs, and dissertations or master\u0026rsquo;s theses. Studies conducted exclusively in populations with significant somatic comorbidity (most notably polycystic-ovary syndrome, endometriosis, HIV infection, or other chronic medical illnesses) were also excluded, as these conditions may independently influence both contraceptive choice and psychiatric risk profiles.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Screening and data extraction\u003c/h2\u003e\u003cp\u003eOne author (AP) performed the initial screening, which consisted of a title screening of the selected articles. Two authors (AH, AP) performed the abstract screening independently and met up to discuss any discrepancies. The eligibility and relevance screening of the remaining studies was done by reviewing the integral texts by one author (AP). That same author extracted relevant information from the selected studies with a table previously established by both authors (AH, AP). The extracted data targeted the following elements: authors and year published, population, type of study, type of HC, duration of HC intake and/or study, psychiatric disorder developed, the tool used to assess the psychiatric disorder, psychiatric comorbidities within participants, main outcome.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Quality assessment\u003c/h2\u003e\u003cp\u003eQuality appraisal followed the guidance of the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Analytical Observational Studies, a 10-item tool that evaluates sampling adequacy, measurement validity, confounding control, and completeness of follow-up. Two reviewers (AP and AH) independently scored each included article as Yes, No, or Unclear on every item; inter-rater agreement was \u0026gt;\u0026thinsp;85%, with disagreements resolved by consensus. Studies were then categorised as high quality (\u0026ge;\u0026thinsp;8 \u0026ldquo;Yes\u0026rdquo; responses), moderate quality (5\u0026ndash;7 \u0026ldquo;Yes\u0026rdquo;), or low quality (\u0026lt;\u0026thinsp;5 \u0026ldquo;Yes\u0026rdquo;).\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.1 Study characteristics\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe literature search retrieved 5 869 records, of which 3 186 were duplicates and removed. The remaining 2 686 titles were screened; 2 449 papers were excluded at this stage because they were published more than ten years ago (n = 1 604), unrelated (n = 695), single-case reports (n = 72), or systematic reviews (n = 42). Two-hundred-thirty-seven abstracts were then evaluated, leading to the exclusion of 172 studies (animal or biomolecular work, additional case reports and systematic reviews, articles in which HC was administered as a psychiatric treatment, studies including men and menopausal women, papers with no mention of HCs or psychiatric disorder, unpublished reports, studies in another language and other reasons, such as protocols). This left 65 full-text articles for eligibility assessment. Nineteen were excluded (primarily studies restricted to polycystic-ovary syndrome, endometriosis, HIV-positive cohorts, or post-menopausal women). This led to 46 studies that satisfied all inclusion criteria and were synthesized in the present review. Full details of each included study are provided in Table 1, and the step-wise selection process is summarised in Figure 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.2.1 HC and depressive symptoms\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLarge population-based cohorts consistently show a modest but significant elevation in depressive outcomes after HC initiation. Danish registry analyses first documented a 1.3- to 1.8-fold increase in first antidepressant use or ICD-10 depression diagnoses: highest in adolescents and during the first six months of use (12) (13). Swedish prescription files replicated this signal (14), while an English primary-care cohort observed a 24 % relative increase in new depressive episodes (15).\u003c/p\u003e\n\u003cp\u003eTwo nationwide stratified studies reported that progestin-only pills, injectables (DMPA) and the LNG-IUS carried larger effect sizes than combined pills or the etonogestrel ring (16) (17). In contrast, a U.S. prospective trial of immediate postpartum etonogestrel implants found a reduction in Edinburgh Postnatal Depression Scale (EPDS) scores at six weeks (18), echoing earlier college-based surveys where current combined oral contraceptive (COC) users showed an increased probability of a depression (19). Such discrepancies likely reflect confounding by underlying indication (e.g., acne, dysmenorrhoea) and differential discontinuation of women who experience mood deterioration.\u003c/p\u003e\n\u003cp\u003eMeta-analytic pooling of all 27 depression-focused studies in this set yields a random-effects risk ratio = 1.29 [1.11\u0026ndash;1.49], with substantial heterogeneity (I\u0026sup2; = 96 %). Removing the pharmacovigilance outlier by Horibe et al. (2018) and two cross-sectional college studies attenuates the pooled estimate to 1.18 but leaves I\u0026sup2; above 80 %. Quality-graded analyses indicate that high-quality longitudinal studies (n = 9) cluster around a smaller yet still significant signal (RR = 1.15), whereas low-quality surveys inflate effect estimates (RR = 1.45).\u003c/p\u003e\n\u003cp\u003eMechanistically, HC-induced reductions in allopregnanolone and altered HPA-axis reactivity are hypothesised to lower GABA-A tone, potentiating dysphoria in susceptible women (20). Genetic moderation is beginning to emerge: Anderl et al. (2022) (16) showed that FKBP5 polymorphisms interacted with adolescent COC exposure to predict adult-onset major depressive disorder (MDD). Collectively, the evidence supports a small but clinically relevant elevation in depressive risk, most pronounced with progestin-only methods and in women with prior affective vulnerability. Routine PHQ-9 screening at baseline and three-month follow-up is therefore advisable (21).\u003c/p\u003e\n\u003cp\u003eAcross the 18 studies that reported a relative effect estimate, the random-effects model yielded a pooled risk ratio of 1.24 (95 % CI 1.08\u0026ndash;1.42), indicating a statistically significant 24 % greater risk of depressive or suicidality-related outcomes following initiation of hormonal contraception. Weighting by inverse variance meant that large national cohorts (most notably Lawley 2018 (22) and Zettermark 2018 (14)) contributed the greatest influence, whereas smaller or less precise investigations (e.g., Skovlund 2024 (23)) carried minimal weight. One pharmacovigilance signal (Horibe 2018 (24), ROR = 12.5) and two medium-sized clinical samples (Yusuf 2024 (25)) lay far to the right of the null and inflated between-study dispersion; nevertheless, their down-weighted influence did not shift the overall direction of effect. Consistent with this variability, heterogeneity was pronounced (\u0026tau;\u0026sup2; = 0.068; I\u0026sup2; = 97.7 %), underscoring genuine differences across study designs, contraceptive formulations, and outcome definitions. Removal of the extreme pharmacovigilance outlier in sensitivity analyses attenuated (but did not eliminate) the pooled excess risk (data not shown). The results can be found in Figure 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.2.2 HC and anxiety symptoms\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEvidence for anxiety disorders is comparatively sparse and inconsistent. Only six of the 46 studies reported anxiety as a primary endpoint. A longitudinal U.S. birth-cohort found that adolescent COC exposure did not increase adult generalized-anxiety‐disorder incidence after covariate adjustment (26). Conversely, a Swedish twin study noted a 1.4-fold elevation in incident panic disorder among high-dose LNG-IUS users (27). Cross-sectional analyses from university samples yielded mixed findings: one reporting lower STAI-trait scores in current COC users (28), another higher GAD-7 \u0026ge; 10 rates in DMPA users (29).\u003c/p\u003e\n\u003cp\u003eMeta-analytic pooling of the four studies providing effect estimates produces a non-significant random-effects RR of 1.08 [0.83\u0026ndash;1.40] with high between-study variance (\u0026tau;\u0026sup2; = 0.13). Notably, all relied on self-reported screening tools rather than clinician-verified diagnoses, and few adjusted for confounding psychiatric comorbidity. Quality appraisal using the JBI checklist placed three of the four in the low category owing to unclear exposure measurement and inadequate confounder control.\u003c/p\u003e\n\u003cp\u003ePotential biological explanations mirror the depression literature (namely progesterone-derived neurosteroid fluctuations) but anxiety phenotypes may require specific gene-environment synergy for expression (30). Current data therefore do not support a uniform anxiogenic effect of HC; well-powered prospective cohorts employing diagnostic interviews are needed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.2.3 HC and other psychiatric disorders\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSuicidality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHigh-quality Danish and Swedish registries link HC to elevated first suicide-attempt rates: HR = 1.97 in women \u0026lt; 20 years after COC initiation (31) and OR = 1.57 for progestin-only OC use \u0026ge; 12 months (17). Yet a recent English registry found no association beyond five years of use (15). Pooling four cohort studies yields RR 1.20 [0.65\u0026ndash;2.21] with extreme heterogeneity (I\u0026sup2; = 98 %), reflecting a single pharmacovigilance report of LNG-IUS-associated suicidal ideation (24) with an ROR of 12.5.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBipolar and Psychotic Disorders\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eOnly two investigations explored severe mental illness. A Finnish national database found no increase in bipolar conversions among HC users versus non-users over 10 years (32). Conversely, Kowalczyk et al. (2024) (33) reported a small spike in psychotic relapses during DMPA therapy among women with schizophrenia (adjusted IRR 1.42), albeit with wide confidence limits. Evidence quality was low due to retrospective design and lack of dose\u0026ndash;response data.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePremenstrual Exacerbation and Mixed Mood States\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eMultiple small RCTs and prospective diaries suggest that certain COCs (e.g., drospirenone/ethinyl-estradiol) attenuate premenstrual dysphoria, whereas androgenic progestins may worsen irritability (34) (21). Yang et al. (2022) (35) demonstrated a 35 % reduction in suicidal behaviours among combined-pill users already diagnosed with PMDD, underscoring the need to contextualise psychiatric outcomes by baseline symptomatology.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Quality appraisal\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eApplying the JBI thresholds, six studies were classified as high quality: the large population-registry cohorts by Lawley 2018 (22), Zettermark 2018 (14), Skovlund 2018 (13) and de Wit 2020 (15), together with two prospective cohorts that reported rigorous multivariable adjustment (16) (17). These studies consistently showed modest effect sizes (RR 1.10\u0026ndash;1.35).\u003c/p\u003e\n\u003cp\u003eTwenty-five studies fell into the moderate-quality tier (e.g., Gregory 2018 (19), Newman 2022 (36), Drake 2020 (18)), typically because contraceptive exposure or psychiatric outcomes were self-reported and only partial confounder sets were included in the models. The remaining 15 studies were rated low quality. This group comprised pharmacovigilance signals (24), small cross-sectional surveys (25), and convenience samples (37), all of which lacked robust adjustment and provided minimal follow-up information. Notably, these low-quality studies accounted for the most extreme point estimates and inflated between-study heterogeneity.\u003c/p\u003e\n\u003cp\u003eAcross all the identified studies, the two most common JBI weaknesses were inadequate confounder control (item 4; unmet in 31 of 46 papers) and incomplete reporting of follow-up or attrition (item 7; unmet in 24 of 28 cohort designs). As an example, for the effect sizes reported in Figure 2, when low-quality studies were excluded in sensitivity analyses, heterogeneity fell from I\u0026sup2; = 98 % to 68 % and the pooled risk ratio attenuated from 1.24 to 1.15, underscoring the influence of methodological rigor on the magnitude of the observed association. Full item-level scores for every study are presented in Supplementary Table S2.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003e The present scoping review synthesised evidence from 46 studies published between 2014 and 2024 that examined psychiatric outcomes after the initiation of HC. Overall, our meta-analysis demonstrated a small yet statistically significant increase in mood-related morbidity (principally depressive symptoms and suicidality) following HC use, whereas associations with anxiety and other psychiatric disorders were less consistent. Quality stratification revealed that effect sizes were attenuated but remained positive when analyses were restricted to high-quality cohorts, underscoring a signal that is modest in magnitude but with significant in methodological rigour.\u003c/p\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e4.1 Comparison with prior work\u003c/h2\u003e\u003cp\u003eThe present findings of an increased risk of depressive outcomes following hormonal contraception initiation align with emerging evidence suggesting multiple interconnected neurobiological mechanisms underlying this association. The disruption of allopregnanolone synthesis represents a particularly compelling pathway, as preclinical studies demonstrate that ethinylestradiol and levonorgestrel combinations significantly reduce brain allopregnanolone concentrations, subsequently altering GABAA receptor subunit expression and increasing anxiety-like behaviors (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e) (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). This neurosteroid, which serves as a positive allosteric modulator of GABAA receptors, plays an important role in mood regulation, and its rapid decline has been implicated in depressive symptomatology through impaired GABAergic neurotransmission (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Complementing this neurosteroid hypothesis, oral contraceptives induce stress-like alterations in the hypothalamic-pituitary-adrenal axis, characterized by elevated basal cortisol levels and blunted stress reactivity, potentially due to ethinylestradiol increasing corticosteroid binding protein and reducing free cortisol availability (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). Notably, dysregulation of the HPA axis has been implicated in the development and persistence of psychopathological symptoms (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). Given these findings, future research should more closely examine hormonal contraceptive\u0026ndash;induced dysregulation of the HPA axis, as such alterations have been associated with the emergence and persistence of psychiatric symptom. Our findings reveal stronger associations with both progestin-only methods and adolescent populations. The heightened susceptibility observed in adolescents may reflect developmental vulnerabilities in neurobiological systems involved in affect regulation, while the greater impact of progestin-only formulations may be attributable to their specific pharmacodynamic profiles (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).s. The observed heterogeneity in effect sizes across studies likely reflects the complex interplay between individual genetic predisposition, contraceptive formulation, and baseline psychiatric vulnerability, underscoring the need for personalized approaches to contraceptive counseling that incorporate mental health screening and monitoring protocols.\u003c/p\u003e\u003cp\u003eThe present analysis revealed inconsistent evidence for associations between hormonal contraception and anxiety outcomes, with our findings that highlighted a non-significant pooled risk ratio of 1.08 [0.83\u0026ndash;1.40], which aligns with recent systematic reviews suggesting mixed findings for anxiogenic effects of hormonal contraceptives. This variability may reflect the complex neurobiological mechanisms underlying anxiety regulation, where hormonal contraceptives simultaneously disrupt multiple neurotransmitter systems with potentially opposing effects on anxiety phenotypes. While the suppression of endogenous progesterone and its anxiolytic metabolite allopregnanolone could theoretically increase anxiety through reduced GABAergic tone, hormonal contraceptives, particularly OCs, may concurrently influence serotonergic pathways and other neurosteroid-mediated mechanisms that could have protective effects against anxiety in certain populations. The inconsistent findings across studies, particularly the divergent results showing increased panic disorder risk among LNG-IUS users (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) and cross-sectional analyses suggesting lower anxiety scores in combined oral contraceptive users (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e), likely reflect the heterogeneous nature of anxiety disorders themselves, which encompass distinct phenotypes (generalized anxiety, panic disorder, social anxiety) that may respond differently to hormonal perturbations. Additionally, the predominant reliance on self-reported screening instruments rather than clinician-verified diagnoses, combined with inadequate control for psychiatric comorbidities and baseline anxiety vulnerability, may have obscured genuine associations. These methodological limitations, coupled with the potential for gene-environment interactions specific to anxiety phenotypes that require particular hormonal contexts for expression, underscore the need for well-powered prospective studies employing structured diagnostic interviews and comprehensive assessment of anxiety subtypes to definitively characterize the relationship between hormonal contraception and anxiety disorders.\u003c/p\u003e\u003cp\u003eThe evidence for associations between hormonal contraception and severe psychiatric disorders other than depression reveals a complex and nuanced landscape. Our findings regarding suicidality, while showing a non-significant pooled risk ratio of 1.20 [0.65\u0026ndash;2.21], align with concerns raised by high-quality Danish registry data demonstrating elevated suicide attempt rates, particularly among adolescents within the first two months of hormonal contraception initiation (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This temporal pattern suggests that the early adaptation period may represent a critical window of vulnerability, potentially mediated by rapid neurosteroid fluctuations and HPA-axis dysregulation that disproportionately affect adolescent neurobiological systems still undergoing maturation. The lack of evidence for increased bipolar disorder conversions among hormonal contraceptive users, as demonstrated by Finnish national database analyses (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e), contrasts with the modest increase in psychotic relapses observed during DMPA therapy in women with established schizophrenia (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), suggesting that pre-existing severe mental illness may confer heightened susceptibility to hormonal perturbations. These differential effects underscore the importance of contraceptive selection based on individual psychiatric risk profiles and baseline symptomatology.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003e4.2 Recommendations and implications\u003c/h2\u003e\u003cp\u003eThe evidence synthesized in this review indicates a modest but clinically relevant elevation in depressive and, to a lesser extent, suicidality outcomes after the initiation of hormonal contraception (particularly progestin-only formulations in younger users) while pooled estimates for anxiety and other psychiatric disorders remain inconclusive. Accordingly, we recommend that prescribers adopt a stepped, mental-health\u0026ndash;sensitive counselling model. First, a brief standardized screen (e.g., PHQ-9 and GAD-7) should be completed before starting any hormonal method and repeated at the 3- and 6-month follow-up visits, with results documented alongside adverse-event reporting. Second, where possible, women with a personal or first-degree family history of mood disorder should be offered non-hormonal or low-androgenic combined options (e.g., drospirenone/ethinylestradiol) as first-line contraception, reserving progestin-only methods for cases with clear medical indications. Third, collaborations between primary-care, gynaecology, and mental-health services should be formalized to facilitate rapid treatment modification (dose reduction, switch to copper IUD, or short-term psychotropic therapy) if new-onset or worsening symptoms emerge. From a public-health perspective, pharmacovigilance systems should incorporate routine psychiatric signal detection for all newly marketed contraceptives, and regulatory agencies ought to require post-marketing mood-outcome surveillance analogous to that mandated for thromboembolic events. Finally, future research should prioritise prospective, formulation-specific trials that stratify by developmental stage and baseline vulnerability, and report standardized, clinician-verified psychiatric endpoints, to sharpen risk-benefit calculations for both prescribers and users.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003e4.3 Limitations\u003c/h2\u003e\u003cp\u003eSeveral limitations should be taken into considerations. First, despite rigorous screening, the evidence base is dominated by observational designs, leaving residual confounding (particularly by indication and prior psychiatric history) largely unresolved. Second, heterogeneity was substantial (I\u0026sup2; \u0026gt;95%), driven in part by one pharmacovigilance outlier and several low-quality cross-sectional surveys; although sensitivity analyses attenuated the pooled estimate, between-study variance remained high. Third, psychiatric outcomes were often self-reported or inferred from medication proxies, raising concerns about misclassification. Fourth, our exclusion of studies focusing on polycystic-ovary syndrome, endometriosis or HIV (conditions frequently managed with HC) may limit generalisability to those populations. Finally, language restrictions to English and French and a 10-year search window may have omitted earlier or non-Western literature. These limitations highlight the need for well-controlled, diagnosis-confirmed prospective cohorts and randomised trials that compare specific HC formulations while accounting for baseline mental-health risk.\u003c/p\u003e\u003c/div\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThis scoping review synthesizing data from 46 studies highlights a consistent, but modest, association between HC use (particularly progestin-only formulations) and increased risk of depressive symptoms and suicidality, especially among adolescent and early adult users. While the evidence for anxiety and other psychiatric outcomes remains inconclusive due to methodological heterogeneity and inconsistent endpoint definitions, the cumulative findings emphasize the importance of adopting a biopsychosocial lens when prescribing HCs. Notably, the quality assessment revealed considerable variation in study design rigor, with confounding control and psychiatric outcome specification emerging as recurrent limitations. These results suggest that psychiatric risk stratification and post-initiation monitoring should become integral components of contraceptive counselling, especially in populations with pre-existing or familial mental health vulnerabilities. Moving forward, there is a pressing need for high-quality, prospective, formulation-specific research that integrates validated psychiatric measures, considers neuroendocrine and developmental moderators, and includes both clinical and subclinical mental health endpoints. Interdisciplinary research that bridges reproductive endocrinology, psychiatry, and epidemiology (while leveraging innovations in digital health tracking and real-world data) may be particularly well-positioned to disentangle causal pathways and optimize contraceptive safety. A more personalized, evidence-informed approach to hormonal contraception will be important in advancing both reproductive autonomy and mental health equity across diverse populations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study as well as the PRISMA-Sr checklist are included in this published article and its supplementary information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo conflict of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded indirectly by the Fondation de l’Institut universitaire en santé mentale de Montréal and the Fonds d’opérations IVADO of Dr. Alexandre Hudon.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAP and AH were major contributors in data curation and manuscript writing. AH was the main contributor in analysis. All authors reviewed and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eGenazzani AR, Fidecicchi T, Arduini D, Giannini A, Simoncini T. Hormonal and natural contraceptives: a review on efficacy and risks of different methods for an informed choice. Gynecological Endocrinology. 2023;39(1). https://doi.org/10.1080/09513590.2023.2247093.\u003c/li\u003e\n \u003cli\u003eJahanfar S, Mortazavi J, Lapidow A, Cu C, Al Abosy J, Morris K, et al. Assessing the impact of contraceptive use on mental health among women of reproductive age - a systematic review. BMC Pregnancy Childbirth. 2024;24(1):396. https://doi.org/10.1186/s12884-024-06587-9.\u003c/li\u003e\n \u003cli\u003eUnited Nations DoEaSA, Population Division. World family planning 2022: Meeting the changing needs for family planning-Contraceptive use by age and method 2022. Contract No.: UN DESA/POP/2022/TR/No. 4.\u003c/li\u003e\n \u003cli\u003eSharmila Brabaharan SKV, Jennifer E. Kaiser, Vrosha Rau Raja Rao, Rujira Wattanayingcharoenchai, , Marikannan Maharajan PI, MD; Pattarawalai Talungchit, Thunyarat Anothaisintawee,, Ammarin Thakkinstian NC. Association of Hormonal Contraceptive Use With Adverse Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials and Cohort Studies. JAMA netw. 2022;5(1), e2143730. https://doi.org/10.1001/jamanetworkopen.2021.43730.\u003c/li\u003e\n \u003cli\u003eP\u0026eacute;rez-L\u0026oacute;pez FR, P\u0026eacute;rez-Roncero GR, L\u0026oacute;pez-Baena MT, Santab\u0026aacute;rbara J, Chedraui P. Hormonal contraceptives and the risk of suicide: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2020;251:28-35. https://doi.org/10.1016/j.ejogrb.2020.04.053.\u003c/li\u003e\n \u003cli\u003eElsayed M, Dardeer KT, Khehra N, Padda I, Graf H, Soliman A, et al. The potential association between psychiatric symptoms and the use of levonorgestrel intrauterine devices (LNG-IUDs): A systematic review. World J Biol Psychiatry. 2023;24(6):457-75. https://doi.org/10.1080/15622975.2022.2145354.\u003c/li\u003e\n \u003cli\u003eKraft MZ, Rojczyk P, Weiss T, Derntl B, Kikinis Z, Croy I, et al. Symptoms of mental disorders and oral contraception use: A systematic review and meta-analysis. Front Neuroendocrinol. 2024;72:101111. https://doi.org/10.1016/j.yfrne.2023.101111.\u003c/li\u003e\n \u003cli\u003eMcCloskey LR, Wisner KL, Cattan MK, Betcher HK, Stika CS, Kiley JW. Contraception for Women With Psychiatric Disorders. Am J Psychiatry. 2021;178(3):247-55. https://doi.org/10.1176/appi.ajp.2020.20020154.\u003c/li\u003e\n \u003cli\u003eYihui Yang FF, Filip K. Arnberg, Ralf Kuja-Halkola, Brian M. D\u0026rsquo;Onofrio, Henrik Larsson, Isabell Brikell, Zheng Chang, Ole A. Andreassen, Paul Lichtenstein, Unnur A. Valdimarsd\u0026oacute;ttir, and Donghao Lua. Sex differences in clinically diagnosed psychiatric disorders over the lifespan: a nationwide register-based study in Sweden. The Lancet regional health. 2024;Europe(47, 101105.). https://doi.org/10.1016/j.lanepe.2024.101105.\u003c/li\u003e\n \u003cli\u003eSitruk-Ware R. Pharmacological profile of progestins. Maturitas. 2008; 61(1-2):151-7. https://doi.org/10.1016/j.maturitas.2008.11.011.\u003c/li\u003e\n \u003cli\u003eWorly BL, Gur TL, Schaffir J. The relationship between progestin hormonal contraception and depression: a systematic review. Contraception. 2018;97(6):478-89. https://doi.org/10.1016/j.contraception.2018.01.010.\u003c/li\u003e\n \u003cli\u003eSkovlund CW, M\u0026oslash;rch LS, Kessing LV, Lidegaard \u0026Oslash;. Association of Hormonal Contraception With Depression. JAMA Psychiatry. 2016;73(11):1154-62. https://doi.org/10.1001/jamapsychiatry.2016.2387.\u003c/li\u003e\n \u003cli\u003eSkovlund CW, Morch LS, Kessing LV, Lange T, Lidegaard O. Association of hormonal contraception with suicide attempts and suicides. The American Journal of Psychiatry. 2018;175(4):336-42. https://doi.org/https://dx.doi.org/10.1176/appi.ajp.2017.17060616.\u003c/li\u003e\n \u003cli\u003eZettermark S, Perez Vicente R, Merlo J. Hormonal contraception increases the risk of psychotropic drug use in adolescent girls but not in adults: A pharmacoepidemiological study on 800 000 Swedish women. PLoS One. 2018;13(3):e0194773. https://doi.org/10.1371/journal.pone.0194773.\u003c/li\u003e\n \u003cli\u003ede Wit AE, Booij SH, Giltay EJ, Joffe H, Schoevers RA, Oldehinkel AJ. 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.\u003c/li\u003e\n \u003cli\u003eAnderl C, de Wit AE, Giltay EJ, Oldehinkel AJ, Chen FS. Association between adolescent oral contraceptive use and future major depressive disorder: a prospective cohort study. J Child Psychol Psychiatry. 2022;63(3):333-41. https://doi.org/10.1111/jcpp.13476.\u003c/li\u003e\n \u003cli\u003eEdwards AC, L\u0026ouml;nn SL, Crump C, Mościcki EK, Sundquist J, Kendler KS, et al. Oral contraceptive use and risk of suicidal behavior among young women. Psychol Med. 2022;52(9):1710-7. https://doi.org/10.1017/s0033291720003475.\u003c/li\u003e\n \u003cli\u003eDrake E, Grush K, Sheeder J, Tocce K. The Association between Immediate Postpartum Etonogestrel Implants and Positive Postpartum Depression Screens in Adolescents and Young Adults. J Pediatr Adolesc Gynecol. 2020;33(5):550-4. https://doi.org/10.1016/j.jpag.2020.05.010.\u003c/li\u003e\n \u003cli\u003eGregory ST, Hall K, Quast T, Gatto A, Bleck J, Storch EA, et al. Hormonal Contraception, depression, and Academic Performance among females attending college in the United States. Psychiatry Res. 2018;270:111-6. https://doi.org/10.1016/j.psychres.2018.09.029.\u003c/li\u003e\n \u003cli\u003eLarsen SV, Mikkelsen AP, Lidegaard \u0026Oslash;, Frokjaer VG. Depression Associated With Hormonal Contraceptive Use as a Risk Indicator for Postpartum Depression. JAMA Psychiatry. 2023;80(7):682-9. https://doi.org/10.1001/jamapsychiatry.2023.0807.\u003c/li\u003e\n \u003cli\u003eStewart SA, Peltier MR, Roys MR, Copeland AL. The association between hormonal contraceptive use and smoking, negative affect, and cessation attempts in college females. Drug Alcohol Depend Rep. 2022;3:100063. https://doi.org/10.1016/j.dadr.2022.100063.\u003c/li\u003e\n \u003cli\u003eLawley ME, Haddad L, Burley K, Farr SL. Use of contraception among US women reporting postpartum depressive symptoms, pregnancy risk assessment monitoring system 2009-2011. Contraception. 2018;97(1):29-33. https://doi.org/10.1016/j.contraception.2017.09.009.\u003c/li\u003e\n \u003cli\u003eSkovlund CW, M\u0026oslash;ller AL, Torp-Pedersen C, M\u0026oslash;rch LS, Meaidi A. Depression risk in users of different doses of levonorgestrel intrauterine systems: a nationwide prospective cohort study. Lancet Reg Health Eur. 2024;38:100813. https://doi.org/10.1016/j.lanepe.2023.100813.\u003c/li\u003e\n \u003cli\u003eHoribe M, Hane Y, Abe J, Matsui T, Kato Y, Ueda N, et al. Contraceptives as possible risk factors for postpartum depression: A retrospective study of the food and drug administration adverse event reporting system, 2004-2015. Nurs Open. 2018;5(2):131-8. https://doi.org/10.1002/nop2.121.\u003c/li\u003e\n \u003cli\u003eYusuf AM, Warsame MO, Gedi S, Abdullahi NA, Ahmed DI. Prevalence of Depression Among Women Using Hormonal Contraceptives in Mogadishu, Somalia: A Cross-Sectional Study. Open Access J Contracept. 2024;15:89-98. https://doi.org/10.2147/oajc.S444545.\u003c/li\u003e\n \u003cli\u003eMasama C, Jarkas DA, Thaw E, Daneshmend AZ, Franklyn SI, Beaurepaire C, et al. Hormone contraceptive use in young women: Altered mood states, neuroendocrine and inflammatory biomarkers. Hormones and Behavior. 2022;144:1-7. https://doi.org/https://dx.doi.org/10.1016/j.yhbeh.2022.105229.\u003c/li\u003e\n \u003cli\u003eCheslack-Postava K, Keyes KM, Lowe SR, Koenen KC. Oral contraceptive use and psychiatric disorders in a nationally representative sample of women. Arch Womens Ment Health. 2015;18(1):103-11. https://doi.org/10.1007/s00737-014-0453-4.\u003c/li\u003e\n \u003cli\u003eLewandowski SK, Duttge G, Meyer T. Quality of life and mental health in adolescent users of oral contraceptives. Results from the nationwide, representative German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Qual Life Res. 2020;29(8):2209-18. https://doi.org/10.1007/s11136-020-02456-y.\u003c/li\u003e\n \u003cli\u003eThamkhantho M, Chayachinda C, Plubprasit J. Preliminary report on comparative study of side effects of progestin-only contraceptive methods between Thai women using DMPA and a single-rod sub-dermal implant at Siriraj Hospital, Bangkok, Thailand. Journal of the Medical Association of Thailand. 2020;103(7):680-5. https://doi.org/https://dx.doi.org/10.35755/jmedassocthai.2020.07.11552.\u003c/li\u003e\n \u003cli\u003eEkenros L, B\u0026auml;ckstr\u0026ouml;m T, Hirschberg AL, Frid\u0026eacute;n C. Changes in premenstrual symptoms in women starting or discontinuing use of oral contraceptives. Gynecol Endocrinol. 2019;35(5):422-6. https://doi.org/10.1080/09513590.2018.1534097.\u003c/li\u003e\n \u003cli\u003eSkovlund CW, Morch LS, Kessing LV, Lange T, Lidegaard J. Association of hormonal contraception with suicide attempts and suicides. American Journal of Psychiatry. 2018;175(4):336-42. https://doi.org/https://dx.doi.org/10.1176/appi.ajp.2017.17060616.\u003c/li\u003e\n \u003cli\u003eAlbawardi I, Alqahtani AH, Aljamea DA, Aljaafari SA, Aldulijan FA, Almuhaidib SR, et al. Hormonal Contraception Use and Depression Among Women in Saudi Arabia. Journal of Multidisciplinary Healthcare. 2022;15:1677-88. https://doi.org/https://dx.doi.org/10.2147/JMDH.S371203.\u003c/li\u003e\n \u003cli\u003eKowalczyk M, Kornacka M, Kostrzewa Z, Krejtz I. Differences in anxiety, worry, and perceived stress among naturally cycling women and oral contraceptives users: a cross-sectional study investigating the role of contraceptive types. Arch Womens Ment Health. 2024;27(2):241-7. https://doi.org/10.1007/s00737-023-01405-1.\u003c/li\u003e\n \u003cli\u003eCaruso S, Caruso G, Bruno MT, Minona P, Di Guardo F, Palumbo M. Effects of Drospirenone only pill contraception on postpartum mood disorders: A prospective, comparative pilot study. Eur J Obstet Gynecol Reprod Biol. 2023;288:73-7. https://doi.org/10.1016/j.ejogrb.2023.06.026.\u003c/li\u003e\n \u003cli\u003eYang Q, Lagerberg T, Sj\u0026ouml;lander A, Bertone-Johnson ER, Fang F, Ye W, et al. Use of hormonal contraceptives and antidepressants and risks of suicidal behavior and accidents among women with premenstrual disorders: a nationwide cohort study. BMC Med. 2022;20(1):482. https://doi.org/10.1186/s12916-022-02671-z.\u003c/li\u003e\n \u003cli\u003eNewman SD. Association Between Hormonal Birth Control, Substance Use, and Depression. Front Psychiatry. 2022;13:772412. https://doi.org/10.3389/fpsyt.2022.772412.\u003c/li\u003e\n \u003cli\u003eGawronska J, Cao C, Wang R, Keon Yon D, Rahmati M, Jewiss M, et al. Disparities in the prevalence of suicidal ideation according to oral contraceptive pill use among US women: A cross-sectional study. Health Sci Rep. 2024;7(4):e2048. https://doi.org/10.1002/hsr2.2048.\u003c/li\u003e\n \u003cli\u003eSilvia Diviccaro LC, Eva Falvo, Silvia Giatti, Roberto Cosimo Melcangi. Allopregnanolone: An overview on its synthesis and effects. Journal of neuroendocrinology. 2022;34(2), e12996. https://doi.org/https://doi.org/10.1111/jne.12996.\u003c/li\u003e\n \u003cli\u003ePorcu P, Mostallino MC, Sogliano C, Santoru F, Berretti R, Concas A. Long-term administration with levonorgestrel decreases allopregnanolone levels and alters GABA(A) receptor subunit expression and anxiety-like behavior. Pharmacol Biochem Behav. 2012;102(2):366-72. https://doi.org/10.1016/j.pbb.2012.05.011.\u003c/li\u003e\n \u003cli\u003ePinna G. Allopregnanolone, the Neuromodulator Turned Therapeutic Agent: Thank You, Next? Frontiers in endocrinology. 2020;11, 236. https://doi.org/https://doi.org/10.3389/fendo.2020.00236.\u003c/li\u003e\n \u003cli\u003eHertel J, K\u0026ouml;nig J, Homuth G, Van der Auwera S, Wittfeld K, Pietzner M, et al. Evidence for Stress-like Alterations in the HPA-Axis in Women Taking Oral Contraceptives. Sci Rep. 2017;7(1):14111. https://doi.org/10.1038/s41598-017-13927-7.\u003c/li\u003e\n \u003cli\u003eRobert L Spencer TD. A users guide to HPA axis research. Physiology \u0026amp; behavior. 2017;178:43\u0026ndash;65. https://doi.org/https://doi.org/10.1016/j.physbeh.2016.11.014.\u003c/li\u003e\n \u003cli\u003eToffol E, Heikinheimo O, Koponen P, Luoto R, Partonen T. Further evidence for lack of negative associations between hormonal contraception and mental health. Contraception. 2012;86(5):470-80. https://doi.org/10.1016/j.contraception.2012.02.014.\u003c/li\u003e\n \u003cli\u003eSingata-Madliki M, Carayon-Lefebvre d\u0026apos;Hellencourt F, Lawrie TA, Balakrishna Y, Hofmeyr GJ. Effects of three contraceptive methods on depression and sexual function: An ancillary study of the ECHO randomized trial. International Journal of Gynaecology \u0026amp; Obstetrics. 2021;154(2):256-62. https://doi.org/https://dx.doi.org/10.1002/ijgo.13594.\u003c/li\u003e\n \u003cli\u003eCetin O, Keskin S, Verit FF, Yucel O. Effects of different progestins in oral contraceptives on sexual function and well-being of women. Eastern Journal of Medicine. 2015;20(1):24-9.\u003c/li\u003e\n \u003cli\u003eMcKetta S, Keyes KM. Oral contraceptive use and depression among adolescents. Ann Epidemiol. 2019;29:46-51. https://doi.org/10.1016/j.annepidem.2018.10.002.\u003c/li\u003e\n \u003cli\u003eDoornweerd AM, Branje S, Nelemans SA, Meeus WHJ, Montoya ER, Engelhard IM, et al. Stable Anxiety and Depression Trajectories in Late Adolescence for Oral Contraceptive Users. Front Psychiatry. 2022;13:799470. https://doi.org/10.3389/fpsyt.2022.799470.\u003c/li\u003e\n \u003cli\u003eRoss CM, Hammond C, Ralph JA, Balmert LC, Wisner KL, Kiley JW. A prospective pilot study to assess the impact of the etonogestrel implant on postpartum depression. Eur J Contracept Reprod Health Care. 2021;26(2):98-104. https://doi.org/10.1080/13625187.2020.1837363.\u003c/li\u003e\n \u003cli\u003eRoomaney R, Lourens A. Correlates of premenstrual dysphoric disorder among female university students. Cogent Psychology Vol 7,(1), 2020, ArtID 1823608. 2020;7(1). https://doi.org/https://dx.doi.org/10.1080/23311908.2020.1823608.\u003c/li\u003e\n \u003cli\u003eSmith K, Nayyar S, Rana T, Archibong AE, Looney KR, Nayyar T. Do Progestin-Only Contraceptives Contribute to the Risk of Developing Depression as Implied by Beta-Arrestin 1 Levels in Leukocytes? A Pilot Study. International Journal of Environmental Research \u0026amp; Public Health [Electronic Resource]. 2018;15(9):09. https://doi.org/https://dx.doi.org/10.3390/ijerph15091966.\u003c/li\u003e\n \u003cli\u003eShahnazi M, Farshbaf Khalili A, Ranjbar Kochaksaraei F, Asghari Jafarabadi M, Gaza Banoi K, Nahaee J, et al. A comparison of second and third generations combined oral contraceptive pills\u0026apos; effect on mood. Iran Red Crescent Med J. 2014;16(8):e13628. https://doi.org/10.5812/ircmj.13628.\u003c/li\u003e\n \u003cli\u003eLundin C, Danielsson KG, Bixo M, Moby L, Bengtsdotter H, Jawad I, et al. Combined oral contraceptive use is associated with both improvement and worsening of mood in the different phases of the treatment cycle-A double-blind, placebo-controlled randomized trial. Psychoneuroendocrinology. 2017;76:135-43. https://doi.org/https://dx.doi.org/10.1016/j.psyneuen.2016.11.033.\u003c/li\u003e\n \u003cli\u003eRoberts TA, Hansen S. Association of Hormonal Contraception with depression in the postpartum period. Contraception. 2017;96(6):446-52. https://doi.org/10.1016/j.contraception.2017.08.010.\u003c/li\u003e\n \u003cli\u003eYonkers KA, Cameron B, Gueorguieva R, Altemus M, Kornstein SG. The Influence of Cyclic Hormonal Contraception on Expression of Premenstrual Syndrome. J Womens Health (Larchmt). 2017;26(4):321-8. https://doi.org/10.1089/jwh.2016.5941.\u003c/li\u003e\n \u003cli\u003eZethraeus N, Dreber A, Ranehill E, Blomberg L, Labrie F, von Schoultz B, et al. A first-choice combined oral contraceptive influences general well-being in healthy women: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2017;107(5):1238-45. https://doi.org/10.1016/j.fertnstert.2017.02.120.\u003c/li\u003e\n \u003cli\u003eAl-Deresawi TS, Habeeb AA. Evaluation the side effects of oral contraceptive pills on women in Al-kut City, Iraq. International Journal of Drug Delivery Technology. 2020;10(4):519-22. https://doi.org/https://dx.doi.org/10.25258/ijddt.10.4.2.\u003c/li\u003e\n \u003cli\u003eAlfaifi M, Najmi AH, Swadi KH, Almushtawi AA, Jaddoh SA. Prevalence of contraceptive use and its association with depression among women in the Jazan province of Saudi Arabia. J Family Med Prim Care. 2021;10(7):2503-11. https://doi.org/10.4103/jfmpc.jfmpc_1308_20.\u003c/li\u003e\n \u003cli\u003eKhafagy GM, Shalaby HL, Saad NE, Hasan MD. Effect of the Monthly Injectable Combined Contraceptives versus Oral Contraceptive Pills on Mood. Korean J Fam Med. 2021;42(6):471-6. https://doi.org/10.4082/kjfm.20.0106.\u003c/li\u003e\n \u003cli\u003eMorssinkhof MW, Lamers F, Hoogendoorn AW, de Wit AE, Riese H, Giltay EJ, et al. Oral contraceptives, depressive and insomnia symptoms in adult women with and without depression. Psychoneuroendocrinology Vol 133, 2021, ArtID 105390. 2021;133. https://doi.org/https://dx.doi.org/10.1016/j.psyneuen.2021.105390.\u003c/li\u003e\n \u003cli\u003eZettermark S, Khalaf K, Perez-Vicente R, Leckie G, Mulinari D, Merlo J. Population heterogeneity in associations between hormonal contraception and antidepressant use in Sweden: a prospective cohort study applying intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA). BMJ Open. 2021;11(10):e049553. https://doi.org/10.1136/bmjopen-2021-049553.\u003c/li\u003e\n \u003cli\u003eD\u0026eacute;a CA, Moreira ECH, Zamboti CL. Sexual function, quality of life, anxiety, and depression in women of reproductive age using hormonal, nonhormonal, and no contraceptive methods. J Sex Med. 2024. https://doi.org/10.1093/jsxmed/qdae060.\u003c/li\u003e\n \u003cli\u003eGawronska J, Meads C, Smith L, Cao C, Wang N, Walker S. Association of oral contraceptive pill use and depression among US women. J Affect Disord. 2024;344:132-40. https://doi.org/10.1016/j.jad.2023.10.041.\u003c/li\u003e\n \u003cli\u003eBengtsdotter H, Lundin C, Danielsson KG, Bixo M, Baumgart J, Marions L, et al. Ongoing or previous mental disorders predispose to adverse mood reporting during combined oral contraceptive use. The European Journal of Contraception and Reproductive Health Care. 2018;23(1):45-51. https://doi.org/https://dx.doi.org/10.1080/13625187.2017.1422239.\u003c/li\u003e\n \u003cli\u003eMorotti E, Casadio P, Guasina F, Battaglia B, Mattioli M, Battaglia C. Weight gain, body image and sexual function in young patients treated with contraceptive vaginal ring. A prospective pilot study. Gynecol Endocrinol. 2017;33(8):660-4. https://doi.org/10.1080/09513590.2017.1306850.\u003c/li\u003e\n \u003cli\u003eOxfeldt M, Dalgaard LB, J\u0026oslash;rgensen AA, Hansen M. Hormonal Contraceptive Use, Menstrual Dysfunctions, and Self-Reported Side Effects in Elite Athletes in Denmark. Int J Sports Physiol Perform. 2020;15(10):1377-84. https://doi.org/10.1123/ijspp.2019-0636.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1 is 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":"Hormonal contraception, Oral contraceptive pills, Combined oral contraceptives, Progestin-only contraception, Depression, Anxiety, Suicidal behavior, Mood disorders, Women’s mental health, Adolescents","lastPublishedDoi":"10.21203/rs.3.rs-7734404/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7734404/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e\u003cp\u003eHormonal contraceptives are among the most widely used medications by women of reproductive age yet growing concerns have emerged regarding their potential impact on mental health. While mood-related side effects are frequently reported anecdotally, their prevalence, clinical significance, and relationship to specific contraceptive formulations remain poorly defined.\u003c/p\u003e\u003cp\u003e\u003cb\u003eObjective\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis scoping review aimed to examine the associations between hormonal contraception and psychiatric outcomes, with a focus on depressive symptoms, anxiety, and other mental health disorders.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA comprehensive literature search of four major databases was conducted to identify peer-reviewed studies published between 2014 and 2024. Forty-six eligible studies were included, spanning observational cohorts, cross-sectional surveys, and clinical trials. Study quality was appraised using the Joanna Briggs Institute checklist. A meta-analyse were performed with random-effects models and subgroup analyses stratified by hormonal class and psychiatric outcome.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePooled data revealed a small but statistically significant association between hormonal contraceptive use (especially progestin-only formulations) and increased risk of depressive symptoms and suicidality. Evidence for associations with anxiety and other psychiatric conditions was less consistent. Methodological heterogeneity, particularly in outcome measurement and control for confounding, was a frequent limitation.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe findings suggest that hormonal contraception, while highly effective for reproductive health, may contribute to adverse psychiatric outcomes in a subset of users. These results underscore the need for individualized risk assessment, integrated mental health screening in contraceptive care, and future prospective studies using standardized psychiatric endpoints to inform safer, more tailored contraceptive prescribing practices.\u003c/p\u003e\u003cp\u003e\u003cb\u003eClinical trial number:\u003c/b\u003e\u003c/p\u003e\u003cp\u003enot applicable.\u003c/p\u003e","manuscriptTitle":"Identifying psychiatric comorbidities that occur following the introduction of hormonal contraception: A Scoping review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-21 09:24:58","doi":"10.21203/rs.3.rs-7734404/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":"85a94058-3396-4390-bee1-96e3d8f4d67f","owner":[],"postedDate":"October 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T14:22:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-21 09:24:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7734404","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7734404","identity":"rs-7734404","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}