Oral contraceptives may pose greater mood risk for teens

The wide availability of oral contraceptives (OCs) has had a massively positive impact on public health. Though they're generally regarded as a method for preventing unintended pregnancies, they're also prescribed to ease a number of medical conditions — such as premenstrual dysphoric syndrome, endometriosis, polycystic ovarian syndrome — or even to lower the risk of some cancers. 

Over the years, much has been said about the link between OCs and mental health. While they are often prescribed to improve mood stability, investigations have also found they may lead to mood deterioration in some users. A lot of this sort of research, however, has a "healthy user bias": those who discontinue the pill due to adverse mood effects are less likely to be included in analysis. 

New research, which is mindful of this bias, sought to explore the link between depression and OCs in more detail. Writing in Epidemiology and Psychiatric Sciences, a team finds that the first two years of OC use were associated with a higher rate of depression compared to those who had never used the medication. While this risk decreases after those initial years, contraceptive use was still associated with an increased lifetime risk of depression. For those who begin OCs as teens, however, the risks appear to be higher and sustained.

This study looked at data from 264,557 UKB participants identified as women between 37 and 71 years old. Data were gathered from questionnaires, interviews, physical health measures, biological samples, and imaging, as well as from health records, primary care data, and death registry data. 

The team analysed data on exposure to OCs, as well as incidence of depression, which was measured either through verbal interviews, inpatient hospital data, or primary care data. In order to capture symptoms in those who did not seek medical advice, those in the sample who may have experienced depressive side effects but did not receive treatment for them were identified through the UKB mental health questionnaire, which measured prolonged feelings of sadness and prolonged lack of interest in normal activities. 

Analyses revealed that over 80% of those in the sample had used OCs at some point. Compared to those not taking OCs, participants who did tended to have a higher socioeconomic status, and a lower likelihood of family history of depression. They were also more likely to have had sex earlier than those who had never used OCs. Users remained on oral contraceptives for an average of 10 years.

During the first two years of consumption, both adult and teen OC users had an increased rate of depression compared to those who had never used them. Of the whole sample, 24,750 participants had received a diagnosis of depression on follow-up; of the 82,232 participants who also completed the UKB mental health questionnaire, however, 44,605 reported experiencing at least one of the core depressive symptoms. Those who used OCs had a higher lifetime risk of depression than those who had never used them.

Perhaps most startlingly, the authors' analyses revealed that those who started taking OCs before the age of 20 had a staggering 130% higher rate of depressive symptoms than never-users, with those who started OCs in adulthood showing a 92% increase. For adults, these rates declined after two years of use, or after discontinuation — for those who started as teens, though, risk of depression remained heightened throughout their use. 

The team suggest that hormonal fluctuations induced by OCs may be behind these increased rates of depression, particularly in those who are sensitive to changes in hormone levels. The additional impact on those who started OCs as teens, the team hypothesise, could be related to the use of hormones during developmental periods.     

Most OC users, the authors emphasise, tolerate external hormones well and do not experience a negative impact on their mood. Even so, this investigation raises the question as to whether healthcare professionals should consider monitoring for potential mood side effects when providing such medication. Oral contraceptives remain a crucial form of sexual healthcare, and insights such as these provide an opportunity for healthcare professionals to deliver them in the most safe manner possible, and allow patients to make fully informed choices about their care. 

This study, of course, is not without its limitations. First and foremost, there may be recall bias in self-reported data, including estimations of age when starting and finishing contraceptives, which form a vital part of the paper's conclusions about teen OC users. The UKB cohort also consists of a "healthier population" than the general population of the UK, which may mean the findings are not wholly generalisable. Some clinical populations were excluded from the sample, and non-White participants were also underrepresented. Lastly, participants also tended to start contraception in the 1970s and 80s; while similar medications are still available, this does make the data somewhat outdated.

Further investigations seeking to extend these analyses and focus on data from the last few years, and including more types of contraceptive, may provide more current insights. For now, these findings may give clinicians another avenue to improve healthcare outcomes. 

Read the paper in full here.