Ever since birth control pills first became available, researchers have been trying to understand the connection between oral contraceptive use and mood.
A new study led by investigators at Brigham and Women’s Hospital and University Medical Center Groningen (UMCG) and Leiden University Medical Center in the Netherlands adds important, new information by surveying young women about depressive symptoms. Depressive symptoms — such as crying, sleeping excessively, and eating issues — can be far subtler than diagnosed clinical depression.
But by surveying a cohort of more than 1,000 women every three years, investigators have amassed a unique trove of data about these subclinical symptoms.
In a study published in JAMA Psychiatry, investigators report that there was no association between oral contraceptive use and depressive symptom severity in the entire population they studied (ages 16 through 25).
However, they found that 16-year-old girls reported higher depressive symptom severity compared with 16-year-old girls not using oral contraceptives.
“One of the most common concerns women have when starting the pill, and teens and their parents have when an adolescent is considering taking the pill, is about immediate depressive risks,” said corresponding author Anouk de Wit, MD, PhD, MPH, in training, formerly of the Brigham’s Department of Psychiatry.
De Wit is now a trainee in the Department of Psychiatry at UMCG. “Most women first take an oral contraceptive pill as a teen. Teens have lots of challenging emotional issues to deal with so it’s especially important to monitor how they are doing.”
“Depressive symptoms are more prevalent than clinical depression and can have a profound impact on quality of life,” said co-author Hadine Joffe, MD, MSc, vice chair for Psychiatry Research for the Brigham’s Department of Psychiatry and executive director of the Connors Center for Women’s Health and Gender Biology.
“Ours is the first study of this scale to dive deep into the more subtle mood symptoms that occur much more commonly than a depression episode but impact quality of life and are worrying to girls, women and their families.”
To conduct their study, de Wit, Joffe and colleagues analyzed data from female participants in the prospective cohort study, Tracking Adolescents’ Individual Lives Survey (TRAILS), a longitudinal study of teens and young adults from the Netherlands.
Each participant filled out a survey with questions about depressive symptoms, such as crying, eating, sleeping, suicidal ideation, self-harm, feelings of worthlessness and guilt, energy, sadness, and lack of pleasure. Their responses were used to generate a depressive symptom severity score.
Across the entire cohort of 1,010 participants ages 16 to 25 analyzed, the team found no association between oral contraceptive use and depressive symptom severity.
However, they did find that, on average, 16-year-old participants who were using oral contraceptives had depressive symptom severity scores that were 21 percent higher than those who were not taking oral contraceptives.
They reported more crying, more sleeping and more eating problems than their counterparts.
The authors note that the association between oral contraceptive use and depressive symptoms may be bidirectional: oral contraceptive use may contribute to symptom severity, more severe symptoms may prompt teens to begin taking oral contraceptives, or both.
Observational studies, such as this one, cannot determine the direction of causality.
“Because of the study design, we can’t say that the pills cause mood changes, but we do have evidence suggesting that sometimes the mood changes preceded the use of the pill and sometimes the pill was started before the mood changes occurred,” said de Wit.
Another limitation that the authors note is that the Dutch are a relatively homogenous population — it remains to be seen if these results would be the same in a more diverse population.
The authors also point out several strengths to the study, including its large size and established, well-characterized cohort. In addition, the research focuses on symptoms that may be of concerns to teens, parents and clinicians.
However, they did find that, on average, 16-year-old participants who were using oral contraceptives had depressive symptom severity scores that were 21 percent higher than those who were not taking oral contraceptives.
“The magnitude of the association was small, and these depressive symptoms are mild enough that they did not constitute clinical or major depression. However, these mood changes were seen in oral contraceptive-using adolescents, who are a vulnerable population,” said Joffe.
“These concerns much be weighed against the bigger risk of lack of contraception leading to unintended pregnancies in teenagers and pregnancy complications including a potential postpartum depression.”
Other forms of birth control known as long-acting reversible contraceptives (LARC), such as intrauterine devices (IUDs), deliver hormone exposure to the local uterine. The investigators are interested in following up to determine if hormone exposure that does not go throughout the whole body and brain is less associated with depressive symptoms.
“Oral contraceptive users, parents and health care providers should be aware of the increased likelihood of presence of depressive symptoms as it may affect quality of life and adherence to oral contraceptive use,” said de Wit.
Funding: Joffe is supported by grants from the National Institutes of Health, Merck Investigator Studies Program, Pfizer, Que-Oncology, NeRRe/KaNDy, and previously SAGE to conduct research unrelated to this report. She is also a consultant for Merck, NeRRe/KaNDy, Sojournix, and, previously, SAGE and Mitsubishi Tanabe.
Use of oral contraceptive pills (OCPs) is common: 80% of women in the United States report using OCPs [1]. OCPs are a popular choice due to their ease of use, variety of formulations, and desirable side effect profile [2]. Among young women, 22% of those aged 15–24 years report using any contraception, and OCPs are the most commonly used method [3]. Because OCP use is widespread, a small increased risk of detrimental effects can have a large clinical impact.
Women have twice the risk of depressive disorders as men [4], [5]. Evidence is needed for factors that are both more common among women and also may increase the risk of depressive disorders; such factors include exogenous hormone use [5]. OCPs contain estrogen and progesterone, both of which have purported associations with mood [6], [7], [8], [9]. Therefore, it is of particular interest to understand whether users of OCPs may be at higher or lower risk for mood disorders, including depressive disorders, compared with nonusers.
There is no consensus on the role of OCPs in depressive disorders. Periods of estrogen instability—for example, puberty, the postpartum period, and perimenopause—show increased risk of depressive disorders. Some physicians recommend OCPs as off-label treatment for stabilizing mood or preventing depression, including among young women [10], [11], [12], [13]. However, countervailing support suggests that initiating OCPs can lead to mood instability, which could either precipitate or exacerbate depression [14]. Mood changes are the most commonly complained side effect of OCPs and a common reason for discontinuing OCP use [15].
Two Swedish studies found that women prescribed OCPs were at increased risk for a subsequent prescription for antidepressants [16], [17]. A 2016 prospective study using the Danish drug registry found similar results [18]. Confounding by indication is a concern, namely that women may be more likely to be prescribed birth control pills to alleviate mood disorder symptoms, thus these same women are more likely to then develop depression [19]. Furthermore, both receiving a diagnosis of depression as well as receiving medication to treat depression unfortunately occurs among only a minority of individuals who experience depression; using registry data introduces misclassification. Therefore, the apparent relationship between OCP use and depression diagnoses could alternatively be explained by surveillance bias—women who regularly seek physicians’ services are more likely to be prescribed medications in general [20]. Furthermore, individual-level confounders, such as sexual behavior, are not sufficiently accounted for in drug registries [21], [22].
Other observational studies showed OCPs may protect against depressive disorders; others show no relationship [23], [24], [25], [26], [27]. These studies include individuals from the community, account for covariates such as baseline depressive symptoms, and use validated depression screeners. One longitudinal study in Australia demonstrated that women who used OCPs for reasons other than birth control were more likely to experience depressive symptoms than those who used them solely for contraception; the authors suggested that associations between OCP use and increased risk of depressive disorder may be due to features of the OCP users, rather than the medications [26]. These studies are limited, although, by the possibility that women who start feeling depressed or having mood changes cease taking birth control [24], [28], [29], [30], [31]. Should this be the case, women taking OCPs for reasons other than contraception may be less likely to discontinue OCPs. Ultimately, there is not yet a consensus on whether OCPs increase or decrease depression risk, nor to what extent women’s OCP use behaviors confound this relationship.
Most of this research focused on women ages 20–40 years, but depression is a debilitating illness for adolescents. It increases risk for suicide, academic difficulties, future unemployment, and criminal justice system involvement [32], [33]. Incidence of depression precipitously increases during adolescence, which is when sex differences in depression emerge [5]. The surge of physiologic sex steroids during adolescence has been hypothesized to be one driver of the female-male disparity in depression, but birth control use is often initiated during the adolescent years [5]. Coinciding with the increased risk of depression during this period, however, adolescents—especially those who experience early development—navigate sexual debut and many new social-relational insults including harassment, bullying, and sexual assault [34], [35]. To our knowledge, a single randomized controlled trial has examined OCP use and depression in adolescents, comparing OCP use with placebo use among adolescents with dysmenorrhea. It found no effect on depressive symptoms (mean exit-interview depressive symptoms score for placebo: 14.0; mean exit-interview depressive symptoms score for OCP users: 14.4; P = 0.86) [36].
The present study addresses the limited existing data on the OCP-depression relationship among adolescents. We examine whether OCP use is associated with increased risks of development of depression in adolescents. We consider behavioral factors that may confound the relationship, and we test the validity of the proposed mechanism between OCP use and depression.
Source:
Brigham and Women’s Hospital
Media Contacts:
Serena Bronda – Brigham and Women’s Hospital
Image Source:
The image is in the public domain.
Original Research: Closed access
“Association of Use of Oral Contraceptives With Depressive Symptoms Among Adolescents and Young Women”. Anouk E. de Wit, BSc; Sanne H. Booij, PhD; Erik J. Giltay, MD, PhD; Hadine Joffe, MD, MSc; Robert A. Schoevers, MD, PhD; Albertine J. Oldehinkel, PhD.
JAMA Psychiatry doi:10.1001/jamapsychiatry.2019.2838.
