. 2025 Feb 11;16:1–29. doi: 10.2147/OAJC.S431365

Table 1.

Literature Review. To conduct this literature review, we searched the keywords “hormonal contraceptives”, “birth Control”, “affective symptoms”, “depression”, “depressive symptoms”, “PMDD”, “PMDS”, “PMS”, and “mood disorders” in Google Scholar and pubMed, and included papers published between 2014–2024

(a) Review of literature assessing the impact of hormonal contraceptive use on depression and depressive symptoms, published 2014–2024.
Study	Study Design	Sample Type	Exclusions	Study Result	Study Type	Method Limitations	HC Types Assessed	Individual Differences Assessed	Outcomes assessed	Covariates	Mechanisms Suggested
Anderl et. al., 2022¹⁰⁴	Data from prospective cohort study; HC use between 16–19 years used as a predictor for depression in early adulthood	N = 725; Women followed from adolescence to early adulthood	Individuals using sex steroids other than HCs at age 16 or 19; Missing data	Adolescent HC use associated with a small but robust increased risk for experiencing an episode of MDD	Correlational, Population	Assessed presence but not duration of HC use; Lumped HC types; Self-selection; Survivorship bias; No random assignment	OCPs	Age	CIDI (depression)	Age; Ethnicity;SES; History of MDD; BMI; Menstrual pain; Acne; Virginity; Smoking; Stress; Age at menarche; Sexual orientation; OC use at age 25; Depressive symptoms	Gonadal hormones have long-lasting impact on brain and behavior and OCs impact these hormones
Engman et. al., 2018²¹	RCT with HC or placebo for three treatment cycles; Outcomes measured during baseline and third treatment cycle	N = 35; Mean age = 24.9; Women who previously experienced OC-related negative affect	Family history of psychiatric disorders & venous thromboembolism; Use of HCs two months prior to study onset; Ongoing psychiatric disorders; Contraindications for MRI scanning; Pregnancy	Depressive symptoms increased in the HC users, but not among the NC group, (group differences non-significant)	RCT	Intervention period of insufficient length to assess impact on affective symptoms	COC (EE/levonorgestrel)	N/A	Depressive symptoms; resting state functional connectivity; Hormone levels (estradiol and progesterone)	N/A	Regional connectivity influenced by exogenous sex hormones, which in turn, impact mood
Lundin et. al., 2023¹⁰⁵	Nationwide register study; Participants followed until event or 7 years after study onset	N = 792,913; Ages 15–24; Women with and without ADHD diagnoses	Contraindications for HC; Cardiovascular disease; Redeemed prescription of ovulation-stimulating drugs; Systemic lupus	HC use has no influence on depression in women without ADHD, but women with ADHD have an increased risk of developing depression when using HCs	Correlational, Population	Self-selection; Survivorship bias; No random assignment	All	ADHD diagnosis	Depression diagnosis; Prescription of stimulant medication	Medical indication for HC use; Parental history of mental disorders; Education; Age	Core symptoms of ADHD contribute to inconsistent pill consumption, leading to worsened pill side effects for individuals with ADHD
Skovlund et al, 2016²⁵	Nationwide prospective cohort study; Women followed until event or 14 years after study onset, from 2000–2013; RRs calculated for first use of anti-depressant and first diagnosis of depression at psychiatric hospital	Nationwide prospective cohort study (Denmark)	Depression diagnosis or antidepressant prescription before study onset	HC use associated with antidepressant use and first diagnosis of depression; Risks decrease as age increases; HC types associated with differential risks	Correlational, Population	Self-selection; No random assignment	All	Age	First depression diagnosis; Antidepressant use	Edu level; PCOS or endometriosis diagnosis; BMI; Smoking	Progestins may have a negative impact on mood
Newman, 2022⁸⁵	Cross-sectional survey to assess correlations between HC use, substance use, and depression	N = 3,320; Mean age = 19.1; College students	Non-binary or male gender identification	HC users had lower depression scores than NC women	Correlational	Duration of HC use not included in analyses; Self-selection; Survivorship bias; No random assignment	All	Cannabis use; Alcohol use	PHQ-9 (depression)	N/A	Individuals that cannot tolerate HC discontinue use; Potential interaction between cannabis use and HC on depressive symptoms
Lundin et. al., 2017⁵⁶	RCT with HC or placebo for three treatment cycles; Outcome measured daily during baseline and third treatment cycle	N = 178; Ages 18–35	BMI > 30; Contraindications for HC use; Family history Contraindications for HC use; Use of treatments that would compromise uptake or metabolism of the contraceptive; See paper for additional health-related exclusions	HC use correlated with significant premenstrual improvement in depression scores	RCT	Self-selection; Intervention period of insufficient length to assess impact on affective symptoms; Survivorship bias	COCs (estradiol and nomegestrol acetate)	Duration of use; Previous adverse hormonal contraceptive experience	DRSP scores measuring daily depression, anxiety, mood swings, irritability, and decreased interest in usual activities	N/A	Study potentially included greater proportion of women with previous negative experiences of COC, such that population may have confounded results
Johansson et. al., 2023²³	Population-based cohort study; RR calculated for HC use including duration, and outcome measures	N = 264,557; Ages 37–71; Median age at initiating and discontinuing HC use 21 and 32 years, respectively	Medical indication for use (individuals with dysmenorrhoea, endometriosis, PCOS)	HC use increases depression risk, particularly during first 2 years of use; HC use during adolescence may increase risk of depression later in life	Correlational, Population	Lumped HC types, Self-selection, Survivorship bias; No random assignment	All	HC onset; Age; Sibling depression occurrence	First depression diagnosis; UK Biobank mental health questionnaire to assess depression	SES; Number of births; PCOS; Age at menarche; Age at sexual debut; Family history of MDD	Gonadal hormones have long-lasting impact on brain and behavior and HCs impact these hormones
Zettermark et. al., 2018¹⁰⁶	Epidemiological study; Followed from first HC use at baseline until prescription or end of one year follow-up	N = 815,662; Ages 21–30 at baseline	Psychiatric diagnosis in previous four years; Prescription fill of a psychotropic drug in previous four years; Individuals who delivered a child at follow-up	HC use is associated with psychotropic drug use (anxiolytics, hypnotics, sedatives, anti-depressants) among adolescent girls	Correlational	Duration of HC use not included in analyses; Self-selection; Survivorship bias; No random assignment	All	Age; HC type	Psychotropic drug prescription (anxiolytics, hypnotics, sedatives, anti-depressants)	SES	Healthy user bias explains higher incidence of psychotropic drug use in adolescent girls
Lisofsky et. al., 2016¹⁰⁷	Three months of HC use compared with NC group; Outcomes assessed at baseline and end of third cycle	N = 56; Ages 16–33	Use of HCs within six months prior to study; Previous pregnancy; Hormonal disorders; MRI incompatibility; History of psychiatric or neurological illness	HC use is correlated with a decrease in grey matter volume; Grey matter reductions in amygdala linked to mood alterations in HC users	Quasi-Experimental; Correlational	Lumped HC types; Self-selection; Study period of insufficient length to assess impact on affective symptoms; No random assignment	OCs (COC and progesterone-only)	Changes in outcomes from baseline	Hormone levels (estrogen and progesterone levels); Cognitive performance; MRI data (structural + functional connectivity); PANAS (affect)	Age	Special sensitivity of the amygdala to female gonadal hormones
Doornweerd et. al., 2022¹³¹	Data from population cohort study; Participants followed for 9 measurement waves over 11 years	Data from nationwide online assessment survey given to undergraduates	Missing data for HC use	HC use not associated with increase in depression in late adolescence compared with NC group	Correlational	Lumped HC types; Self-selection; No random assignment	All	Age of OC onset	RADS-2 (depressive symptoms)	Age at menarche; Childhood trauma; Neuroticism; SES	Reduction in hormonal fluctuation by OC has protective effects
Gregory et. al., 2018¹³²	Data from nationwide online assessment survey given to undergraduates	N = 349,697; Ages 18–34	N/A	HC use significantly increased probability of depression diagnosis	Correlational, Population	Duration of HC use not included in analyses; Lumped HC types; Self-selection; Survivorship bias; No random assignment	All	Age; Hormonal vs non-hormonal contraceptive use	Depression diagnosis	N/A	N/A
Masama et. al., 2022⁷⁸	Current HC users and NC participants completed outcome measures; Outcomes compared between HC groups and different stages of menstrual cycle in NC group	N = 388; Ages 17–29	Individuals who did not specify HC type	HC users displayed significantly higher depressive scores compared to NC group	Correlational	Duration of HC use not included in analyses; Self-selection; Survivorship bias; No random assignment	All	Menstrual cycle phases	Self-reported anxiety and depression symptoms; Perceived stress; Cortisol; Inflammation	BMI	HPA activity is dysregulated in women taking HCs, altering the HPA axis negative feedback mechanism and culminating in hippocampal cell loss, which could contribute to mental health disturbances
Lundin et. al., 2022²²	National registry study; Women followed until event or 7 years after study onset	N = 739,585; Ages 15–25	Prior antidepressant use; Psychiatric diagnosis; Contraindications for HC use	HC users had lower or no difference in depression risk compared to NC	Correlational, Population	Duration of HC use not included in analyses; Self selection; No random assignment	All	Type of user (users, non-users, never-users, former-users); Type of OC	Depression diagnosis; Antidepressant use	Highest attained edu level; Medical indication for HC; Parental origin; Family history of mental illness; BMI; Smoking history	Precocious sexual behavior and drug use leads to depression
de Wit et. al., 2020¹³³	Three waves of data from prospective cohort study used; HC use and depressive symptoms assessed at ages 16, 19, 22, and 25	N = 1,010; Ages 16–25	Serious health or language problems; Pregnancy; Use of other sex steroids	HCs showed no association with depressive symptoms overall; Adolescent users reported significantly higher depressive symptoms than their NC counterparts, including more crying, hypersomnia, and more eating problems	Correlational, Population	Lumped HC types; Survivorship bias; Self selection; No random assignment	OCPs	HC onset; Age; Duration of use	Youth self-report (depression)	Ethnicity; SES	Sex hormones influence brain development
Albawardi et. al., 2022¹³⁴	Community-based cross-sectional study; Online survey	N = 4,853; Ages 21–45	Depression; Combined use of non-hormonal and hormonal contraceptives	High prevalence of depression among HC users compared with NC group	Correlational	Lumped HC types; Self-selection; Duration of HC use not included in analyses; Survivorship bias; No random assignment	All	Duration of HC use; Depression severity	PHQ-9 (depression)	Age; Previous psychiatric disorders; Previous physical illness; Substance use history	Progestins may have a negative impact on mood
Anderl et. al., 202²⁰	Cross-sectional study on data from national survey; Compared women who first used HCs in adolescence to first use in adulthood and to never users	N = 1,236; Ages 20–39	Missing data	Long term association between adolescent HC use and elevated depression risk in adulthood regardless of current HC use	Correlational, Population	Lumped HC types, Self-selection, Survivorship bias; No random assignment	All	Age of OC onset	CIDI (depression)	Age at menarche; Age at sexual debut; Edu; Marital status; BMI; Endometriosis; Ever use of hormonal medications; Smoking history; Sex of sexual partners	Gonadal hormones have long-lasting impact on brain and behavior and OCs impact these hormones
Zethraeus et. al., 2017¹⁰⁸	RCT with HC or placebo for three months of treatment; Outcomes assessed at baseline and end of third treatment cycle	N = 340; Ages 18–35; BMI 19–30; Regular menstrual cycle (25–33 days); Using non-hormonal contraceptive at the study start; Fluent in Swedish	Smoking; Contraindications for HC use (see paper); History of hormone-dependent cancer; Undiagnosed bleeding; Pregnancy; Sex steroid hormone use during 6 weeks prior to study	No effect of HC use on depressive symptoms	RCT	Intervention period of insufficient length to assess impact on affective symptoms	COCs (EE + levonorgestrel)	Testosterone levels (total and free)	PGWBI; BDI (depression)	N/A	Progestins may have a negative impact on mood
Sultan et. al., 2024¹³⁵	Cross-sectional study	N = 326; Ages 15–49; Women using HCs from one week to one year and non-users included	Depression or family history of depression; Use of psychiatric drugs; Chronic physical illness	No overall difference in depression scores between HC and NC groups, though individual depressive symptoms were significantly higher in HC group, including sadness, reduced libido, feelings of pessimism and failure	Correlational	Duration of HC use not included in analyses; Self-selection; Survivorship bias; No random assignment	All	Duration of HC use	BDI survey to assess depression	Smoking; BMI; Past and family history of mental disorders	Precocious sexual behavior and drug use leads to depression
McKetta et. al., 2019⁸²	Data from nationwide survey; HC use, including duration, associated with outcome measures	N = 4,765; Ages 13–18	Pregnancy	No association between ever using HCs and lifetime depressive disorder, nor current use of HCs and current depressive disorder	Correlational	Self-selection; No random assignment	OCPs	Sexual activity	Diagnostic interview to assess depression	Age; Smoking; Age at sexual debut; BMI; SES	Sex steroids influence neural structures
Cheslack-Postava et. al., 2015⁸³	US national survey data used; cohort study	N = 1,171; Ages 20–39; Former users, former long-term users, and never users included	N/A	Non-significant trend, HC use associated with somewhat reduced odds of depressive diagnosis	Correlational, Population	Duration of HC use not included in analyses; Self-selection; Survivorship bias; No random assignment	OCPs (monophasic vs multiphasic)	OC type	Psychiatric diagnosis	Age; Number of male sex partners last year; Edu; Race/ethnicity; SES; Marital status; Number of live-birth pregnancies; Current or recent pregnancy	Protective effect of HC against various disorders due to stable hormone levels across cycle
Roberts et. al., 2017²⁴	Secondary analysis of military medical insurance records; HC use and outcome measures analyzed in 12 months postpartum	N = 75,528; Postpartum women in US military medical system	N/A	Risk of antidepressant use and MDD diagnosis in post-partum period varies with type of HC used	Correlational	Self-selection; Survivorship bia; No random assignment	All	Type of HC	Depression diagnosis; Antidepressant use	SES; Length of HC use	N/A
Yusuf et. al., 2024¹³⁶	Cross-sectional study conducted between two hospitals	N = 227; Ages 15–49; Married Somalian women	Common mental illness diagnoses; Pregnant women	Significant association between HC use and depression, especially among women with shorter durations of HC use	Correlational	Lumped HC types; Self-selection; Survivorship bias; No random assignment	All	Type of HC use; Duration of HC use; Occupation; Edu level; Income; Age	PHQ-9 (depression)	N/A	N/A
Bengtsdotter et. al., 2018¹⁰⁶	Supplementary analysis of an RCT; Women treated with either HC or placebo during three treatment cycles; Outcomes measured at baseline, two months, and final cycle	N = 202; Ages 18–35; Women with diagnosis for mood/panic/eating disorder; BMI 17–30	Contraindications for HC use; Family history Contraindications for HC use; Use of treatments that would compromise uptake or metabolism of the contraceptive; See paper for additional health-related exclusions	Women with ongoing or previous mental health disorders or risky use of alcohol have significantly greater risk of HC-induced mood symptoms including anxiety, mood swings, and irritability, but not depression or decreased interest in usual activities	RCT	Intervention period of insufficient length to assess impact on affective symptoms	COCs (EE and nomegestrol acetate)	Alcohol use; Previous or ongoing mental health disorders	DRSP scores measuring daily depression, anxiety, mood swings, irritability, and decreased interest in usual activities	N/A	Women with ongoing or previous mood disorders particularly sensitive to estrogen and progesterone effects
(b) Review of literature assessing the impact of hormonal contraceptive use on depression and depressive symptoms, focused on premenstrual disorders (PMDs), published 2014–2024.
Eisenlohr‐Moul et. al., 2017⁷⁰	RCT; HC (EE and DROS) or placebo for three months of treatment; Outcome tracked through all treatment cycles	N = 55; Ages 18–40; Prospectively confirmed women with PMD	N/A	Across all groups PMS symptoms declined significantly	RCT	Intervention period of insufficient length to assess impact on affective symptoms	DROS/EE	Daily symptoms	DRSP to assess daily emotional and physical symptoms	N/A	High placebo response indicates relevance of placebo mechanisms to psychopathology of PMDs
Yonkers et. al., 2017¹³⁷	Secondary analysis of a cohort study with a nested RCT; Used effect sizes to compare outcome between cycle phases in four premenstrual windows	N = 490; Ages 21–35	DROS users; Major depressive episode; Eating disorder; psychotic disorder; Receiving pharmacotherapy for psychiatric disorder; Recreational drugs at least once weekly; Severe suicidal thoughts; Hypersensitive to study compound; Pregnant	HC slightly attenuates menstrual cycle symptom change	Correlational, RCT	Lumped HC types	All	N/A	DRSP to assess daily emotional and physical symptoms	N/A	N/A
Shehata et. al., 2020⁶⁹	RCT; Fluoxetine and HC, just HC, or placebo for six months; Main outcome was improved PMS in final cycle after five cycles of treatment	N = 300; Ages 20–40; Women with severe PMS	Underlying psychiatric disease; BMI >35; Women seeking pregnancy	Combined use of fluoxetine and HC containing DROS is superior to HC use alone in severe PMS	RCT	None	Oral fluoxetine and HC containing DROS	N/A	DRSP to assess daily emotional and physical symptoms; Number of women with improved PMS in final cycle of treatment (after 5 cycles)	N/A	COC inhibits ovarian activity reducing the effect of circulating sex steroids on serotonin, while fluoxetine inhibits serotonin reuptake
Takeda et. al., 2015¹³⁹	Treated with EE and DROS for six cycles; Outcomes assessed at baseline and after three and six cycles of treatment	N = 48; Ages 20–49; Women with dysmenorrhea and premenstrual symptoms of PMS/PMDD	N/A	EE + DROS treatment significantly improved the severity of premenstrual symptoms	Quasi-experimental	Self-selection, Survivorship bias; No random assignment	EE/DROS	Duration of treatment	Premenstrual symptoms (questionnaire)	N/A	Combined OC pills prevent ovulation and stabilize hormone levels attenuating symptoms

Abbreviations: HC, hormonal contraceptive; MDD, major depressive disorder; OCP, oral contraceptive pill; SES, socioeconomic status; BMI, body mass index; RCT, randomized controlled trial; EE, ethinyl estradiol; COC, combined oral contraceptive; ADHD, attention-deficit/hyperactivity disorder; NC, Naturally cycling; OC, oral contraceptive; RR, risk ratio; PHQ-9, Patient Health Questionnaire-9; DRSP, Daily Record of Severity of Problems; CIDI, Daily Record of Severity of Problems; UK, United Kingdom; Edu, education; N/A, not applicable; PCOS, polycystic ovary syndrome; MRI, magnetic resonance imaging; PANAS, Positive and Negative Affect Scale; RADS-2, Reynolds Adolescent Depression Scale, Version 2; HPA, hypothalamic-pituitary-adrenal; BDI, Beck’s Depression Inventory; US, United States; PGWBI, The Psychological General Well-Being Index; PMD, premenstrual disorder; DROS, drospirenone; PMDD, premenstrual dysphoric disorder; PMS, premenstrual syndrome.