Depression is a prevalent health problem affecting U.S. women. Oral contraceptive pills (OCPs) are commonly used for pregnancy prevention, and evidence is mixed regarding any increased risk for incident depression among users, particularly adolescents.
Methods
We examined the relationship between OCP use and depressive disorders among female adolescents using validated, structured interview assessments in a general population sample of adolescents in the National Comorbidity Survey-Adolescent Supplement. Respondents were 4765 female adolescents with no history of pregnancy who reported current OCP use, lifetime OCP use, and age of OCP initiation. Lifetime and current depressive disorders, including major depressive disorder and depressive episodes, were assessed by lay interviewers.
Results
In logistic regression models adjusted for a range of confounders, there was no relationship between ever using OCPs and lifetime depressive disorder (OR 1.10, 95% CI 0.88-1.37), nor current use of OCPs and current depressive disorder (OR 0.82, 95% CI 0.50-1.35). Using survival analysis for age-of-onset data, we found that OCP use is not associated with an increased risk of depressive disorders.
Conclusions
In sum, use of OCPs in a general population sample of adolescents did not increase the risk of depressive disorders.
McKetta Keyes oral contraceptive pill depression adolescents National Comorbidity Survey, OCP use depressive disorder adjusted odds ratio 1.10 no association female teenagers, hormonal contraception mental health 4765 adolescent females structured interview, lifetime major depressive disorder OCP use survival analysis age-of-onset data, current OCP use current depressive disorder OR 0.82 no increased risk, National Comorbidity Survey Adolescent Supplement contraception epidemiology, logistic regression confounders adjusted oral contraceptive depression risk teens, age OCP initiation depressive episode incidence reproductive health epidemiology, oral contraceptive pills pregnancy prevention adolescent no pregnancy history sample, validated structured interview assessment lay interviewers depressive disorders
PMID 30674431 30674431 DOI 10.1016/j.annepidem.2018.10.002 10.1016/j.annepidem.2018.10.002 McKetta et al. 2019, McKetta 2019
Cite this article
McKetta, S., & Keyes, K. (2019). Oral contraceptive use and depression among adolescents. Annals of epidemiology, 29, 46-51. https://doi.org/10.1016/j.annepidem.2018.10.002
McKetta S, Keyes K. Oral contraceptive use and depression among adolescents. Ann Epidemiol. 2019;29:46-51. doi:10.1016/j.annepidem.2018.10.002
McKetta, Sarah, and Katherine Keyes. "Oral contraceptive use and depression among adolescents." Annals of epidemiology, vol. 29, 2019, pp. 46-51.
Brandao BM et al., 2025·Hormones and Behavior·
Open Access
Hormonal contraceptives (HCs) are widely used, yet their effects on emotional and cognitive processes remain poorly understood. This study examined how HC use may influence emotional reactivity, emotion regulation, and emotional memory. Female participants (N = 179), either using HCs (N = 87) or naturally cycling (NC; N = 92), were randomly assigned to one of three groups: no emotion regulation (control), distancing and immersion, or reinterpretation and immersion. The emotion regulation groups completed emotion regulation training in which they viewed emotional images while applying different emotion regulation strategies, followed by a surprise memory test. Overall, HC users showed greater emotional reactivity to emotional images compared to NC participants. Both HC and NC groups successfully applied emotion regulation strategies as measured by changes in emotional affect; however, distancing led to a greater reduction in negative emotions compared to reinterpretation, particularly among HC users. Both HC and NC groups showed better memory for positive images after applying immersion. For negative images, HC users showed reduced memory performance when applying either distancing or reinterpretation, an effect not observed in NC participants. These findings suggest that HC use may influence specific aspects of emotional processing and memory, highlighting the need for more nuanced research on the cognitive and emotional effects of hormonal contraceptives.
Combined oral contraceptives (COCs) possess the ability to alter the normal composition of the gut microbiome and the permeability of the gastrointestinal (GI) tract, which may cause both gut-related and non-gut-related complications. The gut-estrogen axis examines the relationship between estrogens (particularly the active form, estradiol) and the gastrointestinal system and can be attributed to the maintenance of the estrobolome and circulating estradiol levels. The gut-brain axis involves the relationship between the brain and the gastrointestinal system and can be attributed to the gut microbiome in relation to the enteric nervous system (ENS) and serotonin levels. Overall, the introduction of exogenous hormones into an endogenous environment alters the normal balance of both hormones and bacteria. Currently, there is a gap in knowledge regarding the link between COCs and mental health complications such as anxiety and depression, and the diversity in these complications may be related to different types of COCs, their composition, and variations in study populations. This article reviews existing evidence from animal and human studies on the role of COCs in the development of mental health issues through their impact on the gut microbiome.
The combined hormonal contraceptive (CHC) with ethinylestradiol and progestins is the most widely used contraceptive method among young women and is used by millions worldwide. However, uncertainties exist about the risk of ischemic stroke associated with the use of CHCs with low-dose ethinylestradiol (<50-µg ethinylestradiol) and with the newest fourth-generation progestins that have only been sparsely investigated for the risk of ischemic stroke. In this cohort study based on Danish registries covering the entire Danish female population aged 18 to 49 years from 2004 to 2021, we investigated incidence rate ratios (IRRs) of ischemic stroke using CHCs compared with nonuse of hormonal contraceptives. Analyses focused on comparing CHCs based on ethinylestradiol content (30-40versus ≤20-μg ethinylestradiol), progestin generation (second, third, and fourth) in CHCs, and route of administration (monophasic versus sequential). Poisson regression models adjusting for age, education, ethnicity, calendar year, and medication used for risk factors were utilized. In total, 1 711 757 nonpregnant women contributed 14 697 788 person-years to the investigation. For users of CHCs containing <50-µg ethinylestradiol, the adjusted IRR was increased by 1.77 (95% CI, 1.62-1.93) compared with nonusers of hormonal contraceptives. IRR did not differ between CHCs with 30to 40and ≤20-µg ethinylestradiol. Adjusted incidence rate difference between CHC users and nonusers of hormonal contraceptives ranged from 1 in 100 000 women per year in 18 to 24 years of age to 24 in 100 000 women per year in ≥45 years of age. Incidence rate in users of fourth-generation CHCs was 30% lower than that of second-generation CHCs adjusted IRR (0.70 [95% CI, 0.50-0.98]). IRR for users of third-generation CHCs did not differ significantly from that of second-generation users adjusted IRR (1.14 [95% CI, 0.97-1.35]). Use of CHCs was associated with a 1.77 higher IRR of ischemic stroke. IRR did not relate to ethinylestradiol content in users of CHCs with <50-µg ethinylestradiol. IRR was 30% lower in users of fourth-generation than in users of second-generation CHCs.
Hormonal contraception has been linked to mood symptoms and the ability to recognize emotions after short periods of treatment, whereas the mental health of users of long-term hormonal contraceptives has had limited investigation. To evaluate whether short-term hormonal withdrawal, which users of combined oral contraceptives (COCs) undergo once a month (pill pause), was associated with altered mood and emotional recognition in long-term users of COCs. DESIGN, SETTING, This case-control study included a community sample of individuals assigned female sex at birth who identified as women and used COC for 6 months or longer. The control group included women with natural menstrual cycles who otherwise fulfilled the same inclusion criteria. The study was conducted between April 2021 and June 2022 in Salzburg, Austria. COC users and women with natural menstrual cycles were tested twice within a month, once during their active pill phase or luteal phase and once during their pill pause or menses. Negative affect, anxiety, and mental health problems were assessed during each session. The percentage increase in mental health symptoms was calculated during the pill pause compared with that during the active intake phase in COC users. How this change compared with mood fluctuations along the menstrual cycle in women with natural menstrual cycles was assessed. A total of 181 women aged 18 to 35 years (mean [SD] age, 22.7 [3.5] years) were included in the analysis (61 women with androgenic COC use, 59 with antiandrogenic COC use, 60 women with a menstrual cycle not taking COCs). COC users showed a 12.67% increase in negative affect (95% CI, 6.94%-18.39%), 7.42% increase in anxiety (95% CI, 3.43%-11.40%), and 23.61% increase in mental health symptoms (95% CI, 16.49%-30.73%; P < .001) during the pill pause compared with the active intake phase. The effect size of this change did not differ depending on progestin type (negative affect: F1,117 = 0.30, P = .59; state anxiety: F1,117 = 2.15, P = .15; mental health: F1,117 = .16, P = .69) or ethinylestradiol dose (negative affect: F1,57 = .99, P = .32; state anxiety: F1,57 = 2.30, P = .13; mental health: F1,57 = .14, P = .71) was comparable with mood changes along the menstrual cycle in women with natural cycles (negative affect: F2,175 = 0.13, P = .87; state anxiety: F2,175 = 0.14, P = .32; mental health: F2,175 = 0.65, P = .52). Mood worsening during the pill pause was more pronounced in women with higher baseline depression scores (negative affect increase of 17.95% [95% CI, 7.80%-28.10%] in COC users with higher trait depression [BDI >8]). Emotion recognition performance did not differ between active pill phase and pill pause. In this case-control study of long-term COC users, withdrawal from contraceptive steroids during the pill pause was associated with adverse mental health symptoms similar to those experienced by women during menses with withdrawal from endogenous steroids. These results question the use of the pill pause from a mental health perspective. Long-term COC users may benefit more from the mood-stabilizing effects of COCs in cases of continuous intake.