New research has suggested a link between the use of oral contraceptives (OCs) a form of birth control and an increased risk of depression, particularly within the first two years following initiation. The study tracked over 250,000 women from birth to menopause and gathered information about their use of combined contraceptive pills containing both progesterone and estrogen, the timing of the initial depression diagnosis, and the onset of depressive symptoms that were not formally diagnosed.
According to the findings, women who began using these OCs before or at the age of 20 experienced a 130% higher incidence of depressive symptoms, while adult users saw a 92% increase. However, the higher occurrence of depression tended to decline after the first two years of use, except in teenagers who maintained an increased incidence of depression even after discontinuation.
It’s important to note that some experts believe the study’s methodology may be flawed, and previous research has shown inconsistent findings regarding the association between hormonal contraceptives and depression risk. Randomized clinical trials have indicated little or no effect of hormonal contraceptives on mood, but most of these studies didn’t consider previous use of hormonal contraceptives.
The study is based on data collected from participants in the UK Biobank, and most of the participants taking OCs had initiated use during the 1970s/early 1980s when second-generation OCs, containing levonorgestrel and ethinyl estradiol, were predominantly used.
The researchers conducted a time-dependent analysis to compare the effect of oral contraceptive (OC) use during the first two years of initiation with the effect during the remaining years of use in recent and previous users. To address potential familial confounding, they also analyzed a subcohort of female siblings using a regression-based approach known as “Inference about Causation from Examination of Familial Confounding.” This approach uses paired observational data from related individuals to determine causality.
The findings of the study revealed that the first two years of OC use were associated with a higher rate of depression compared to never-users. Although the risk became less pronounced after this period, ever-use of OCs was still linked to an increased lifetime risk for depression. Adolescents who initiated OC use had the highest risk, experiencing a more marked effect than adult users.
However, experts have raised concerns about the study’s methodology and potential flaws. One expert questioned the sibling component of the research, which the authors considered confirming causality. The effect observed in siblings may be important but not necessarily causative, and retrospective recall of OC use and depressive symptoms can be subject to memory bias. Additionally, the researchers did not consider the indication for OC use, as OCs are used to treat various medical conditions, including premenstrual dysphoric disorder.
The study’s reliance on self-reported data and its observational nature limit the ability to infer causation conclusively. The researchers did not explore continuous use or variations in formulations and doses of OCs, which could have significant implications for the outcomes.
As a result, some experts suggest that the study may have methodological issues and may not be sufficient for guiding clinical practice. Despite its findings, further research would be needed to draw more definitive conclusions and address potential limitations.
The study was funded primarily by the Swedish Research Council, the Swedish Brain Foundation, and the Uppsala University Center for Women’s Mental Health during the Reproductive Lifespan. The authors, along with the experts who commented, declared no relevant financial relationships.
Overall, while the study adds to the growing body of research on OC use and depression risk, its limitations highlight the need for cautious interpretation and the importance of conducting more comprehensive and robust studies in the future.