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Contraception · Oral Contraceptives

Population-based cohort study of oral contraceptive use and risk of depression

Johansson T, Vinther Larsen S, Bui M, Ek WE, Karlsson T, Johansson Å

Published June 12, 2023 Epidemiology and Psychiatric Sciences, 32, e39
DOI 10.1017/S2045796023000525 PMID 37303201 PMC PMC10294242

RRM Academy Synopsis

Oral contraceptive use is linked to more depression in UK women

In a cohort of 264,557 UK Biobank women, oral contraceptive use was linked to a higher rate of depression, especially in the first two years of use. Adolescent starters had a higher depression rate more than 2 years after stopping. The authors report sister-pair results consistent with a causal link.

Key Findings

  • In the first 2 years of use, depression rates were higher than in women without use, among those who started at age 20 or younger and those who started later.
  • Ever use of oral contraceptives was associated with a higher lifetime rate of depression than no use (HR = 1.05, 95% CI: 1.01–1.09).
  • Among 82,232 women who completed a mental health questionnaire, ever use was associated with a higher rate of depressive symptoms (HR = 1.27, 95% CI: 1.23–1.30).
  • More than 2 years after stopping, rates were higher in adolescent starters (HR = 1.18, 95% CI: 1.12–1.25), with no significant association in adult starters (HR = 1.00, 95% CI: 0.95–1.04).
  • Among 7,354 sister pairs, a woman's own oral contraceptive use remained associated with her depression diagnosis after adjusting for her sister's use (β′self = 0.48, 95% CI: 0.19–0.76).

Interpretation

This cohort study followed 264,557 UK Biobank women. Researchers tracked each woman's pill use as it changed over time. A sister-pair analysis compared sisters to account for shared family traits. The authors say this result fits a cause-and-effect link between pill use and depression. Most women in this group started oral contraceptives in the 1970s and early 1980s, when second-generation pills were common. The authors note recall bias as a limit, since women reported their own start and stop ages. The findings support more study of pill use and depression risk, especially in women who started as teens.

RRM Context

Restorative reproductive medicine treats the ovulatory cycle as a vital sign and seeks the cause of a cycle problem first. Oral contraceptives are suppressive medications that override the cycle. In UK Biobank women, their use was associated with more depression, especially soon after starting. The adolescent finding bears on how restorative clinicians weigh cycle suppression in young women. The authors cite a hypothesis that teens are more sensitive to hormones.

Our editorial summary of this paper, not the article's abstract.

Abstract

Aim

Research on the effect of oral contraceptive (OC) use on the risk of depression shows inconsistent findings, especially in adult OC users. One possible reason for this inconsistency is the omission of women who discontinue OCs due to adverse mood effects, leading to healthy user bias. To address this issue, we aim to estimate the risk of depression that is associated with the initiation of OCs as well as the effect of OC use on lifetime risk of depression.

Methods

This is a population-based cohort study based on data from 264,557 women from the UK Biobank. Incidence of depression was addressed via interviews, inpatient hospital or primary care data. The hazard ratio (HR) between OC use and incident depression was estimated by multivariable Cox regression with OC use as a time-varying exposure. To validate causality, we examined familial confounding in 7,354 sibling pairs.

Results

We observed that the first 2 years of OC use were associated with a higher rate of depression compared to never users (HR = 1.71, 95% confidence interval [CI]: 1.55-1.88). Although the risk was not as pronounced beyond the first 2 years, ever OC use was still associated with an increased lifetime risk of depression (HR = 1.05, 95% CI: 1.01-1.09). Previous OC use were associated with a higher rate of depression compared to never users, with adolescent OC users driving the increased hazard (HR = 1.18, 95% CI: 1.12-1.25). No significant association were observed among adult OC users who had previously used OCs (HR = 1.00, 95% CI: 0.95-1.04). Notably, the sibling analysis provided further evidence for a causal effect of OC use on the risk of depression.

Conclusions

Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life. Our results are consistent with a causal relationship between OC use and depression, as supported by the sibling analysis. This study highlights the importance of considering the healthy user bias as well as family-level confounding in studies of OC use and mental health outcomes. Physicians and patients should be aware of this potential risk when considering OCs, and individualized risk-benefit assessments should be conducted.

Topics

By this author

Related research

Contraception › Oral Contraceptives › Metabolic Effects
Søren Vinther Larsen
S Larsen
PMID 37303201 37303201 DOI 10.1017/S2045796023000525 10.1017/S2045796023000525 Johansson et al. 2023, Johansson 2023

Keywords

Contraceptives, Oral

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