Recent research, the largest of its kind, has found that women using combined contraceptive pills had more risk of developing depression than those who did not, the pills upping their chances by a substantial 73% during the first two years of use, and among teenagers, likely to result in later-life depression.
In a global perspective, depression is the leading cause of ill health and disability, affecting more than 264m people, with at least 25% of all women and 15% of all men requiring treatment for this at some point in their lives.
That contraceptive pills might have negative effects on mental health and even lead to depression has long been discussed, but until now, the picture emerging from research has not been straightforward.
This study – the widest-ranging to date – followed more than a quarter of a million women from UK BioBank from birth to menopause.
The researchers collected data about women’s use of contraceptive pills, the time at which they were first diagnosed with depression and when they first experienced symptoms of depression without receiving a diagnosis.
The method of contraception studied was combined contraceptive pills, which contain progestogen, a compound resembling the hormone progesterone, and oestrogen. Progestogen prevents ovulation and thickens the cervical mucus to prevent sperms from entering the uterus, while oestrogen thins the uterine lining to hinder the implantation of a fertilised egg.
“Although contraception has many advantages for women, both medical practitioners and patients should be informed about the side-effects identified in this and previous research,” said Therese Johansson of the Department of Immunology, Genetics and Pathology at Uppsala University, one of the researchers leading the study.
According to the study, women who began to use contraceptive pills as teenagers had a 130% higher incidence of symptoms of depression, while the corresponding increase among adult users was 92%.
“The powerful influence of contraceptive pills on teenagers can be ascribed to the hormonal changes caused by puberty. As women in that age group have already experienced substantial hormonal changes, they can be more receptive not only to hormonal changes but also to other life experiences,” said Johansson.
The researchers were also able to see that the increased incidence of depression declined when the women continued to use contraceptive pills after the first two years. However, teenage users still had an increased incidence of depression even after stopping the pill, which was not observed in adult users.
The findings, published in Epidemiology and Psychiatric Sciences, point to a need for healthcare professionals to be more aware of possible links between different systems in the body, such as depression and the use of contraceptive pills.
The researchers said it was important for doctors to inform women – who are considering using contraceptive pills – of the potential risk of depression as a side-effect.
“Since we only investigated combined contraceptive pills in this study, we cannot draw conclusions about other options, such as mini pills, contraceptive patches, hormonal spirals, vaginal rings or contraceptive rods. In a future study, we plan to examine different formulations and methods of administration,” Johansson said.
Study details
Population-based cohort study of oral contraceptive use and risk of depression.
T. Johansson, S. Vinther Larsen, M. Bui, W. Ek, T. Karlsson, Å. Johansson.
Published in Epidemiology and Psychiatric Sciences on 12 June 2023
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 two 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 two 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 two 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 individualised risk–benefit assessments should be conducted.
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