Review of: de Wit AE et al, JAMA Psychiatry 2019;77(1):52–59

Since the dawn of their widespread use in the 1960s, we’ve worried about the impact of oral contraceptives (OCP) on mood. But the research to date has been inconsistent, with studies reporting negative, positive, or no effects on mood. Heterogeneity in study population and design may underlie these discrepancies. This new study uses a longitudinal design to provide some very useful data on the connection between OCP and various depressive symptoms.

The study used data from the Dutch population survey TRAILS (Tracking Adolescents’ Individual Lives Survey), which included 1,010 females aged 16–25 years who had 1–4 assessments of OCP use and depressive symptoms. The researchers used the affective problems scale of the Youth and Adult Self-Report to measure depressive symptoms. Follow-up assessments were conducted at ages 16, 19, 22, and 25 years.

In young women (aged 19, 22, and 25 years), there was no difference in depressive symptoms between OCP users and non-users. But adolescent OCP users (aged 16 years) reported nearly twice as much crying, over 1.5 times more hypersomnia, and about 1.5 times more eating problems compared to non-users even after adjustment for age, ethnicity (Dutch vs non-Dutch), and socioeconomic status. The association between depressive symptoms and adolescent OCP users was weaker, but still present, after adjustment for virginity, acne, menstrual-related pain, stressful event exposure, and depressive symptom scores before OCP use.

This study was notable for its prospective design, 9-year follow-up across multiple time points, and use of a validated questionnaire for depressive symptomatology. Still, we don’t know what indications were cited for these patients (birth control, menstrual irregularities, acne, etc), nor which OCPs were used (eg, progesterone vs mixed progesterone-estrogen). Also, we don’t know if these findings generalize to a non-Dutch population.

CCPR’s Take
We would not merely avoid OCP to reduce depression risk. The strength and mediators of the association between OCP use and depressive symptoms in adolescents remain unclear. OCP use might also be a marker for sexual behavior associated with other psychosocial concerns. OCPs help with dysmenorrhea, premenstrual syndrome, and prevention of unintended pregnancies, and the authors note that OCP use is safer than pregnancy and postpartum depression. Moreover, SSRIs may be helpful or may exacerbate pre- and perimenstrual mood problems. It’s a complicated topic—with each patient we will learn something new.