Hormonal contraceptive use may increase risk of depression

EBM Focus - Volume 11, Issue 41

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Reference - JAMA Psychiatry 2016 Sep 28 early online (level 2 [mid-level] evidence)

  • The potential impact of hormonal contraception on the development of depression is unclear.
  • In a prospective cohort study of 1,061,997 females aged 15-34 years, hormonal contraceptive use was associated with increased risks of depression and antidepressant use. There was also an indication that risks are greater with combination patch and vaginal ring products.
  • These findings suggest that depression may be an adverse side effect of hormonal contraceptive use.

Although hormones are recognized to influence mood, the potential impact of hormonal contraception on the development of depression is unclear. Conflicting results regarding this question are described in 1 longitudinal and 9 cross-sectional studies (reported in JAMA Psychiatry 2016 Sep 28 early online) and two randomized trials performed in a total of 226 women or adolescents from very selective patient groups (Contraception 1995 Dec;52(6):363, Contraception 2007 Apr;75(4):299). A recent prospective cohort study in Denmark involving over 1 million females aged 15-34 years evaluated hormonal contraceptive use and the incidences of diagnosis of depression and antidepressant use by monitoring national registries tracking discharge diagnoses from inpatient and outpatient psychiatric clinics and prescription redemption. Females with a previous psychiatric diagnosis or history of antidepressant use, or with contraindications for hormonal contraception were excluded from the study. Hormonal contraceptive use was defined as any use in the previous 6 months (including current use) and nonuse was defined as either no history of using hormonal contraception or discontinuation for > 6 months. Females who began hormonal contraception during the study contributed to both the exposed and unexposed observation periods.

During a mean follow-up of 6.4 years, 56% of the females used hormonal contraceptives. There were a total of 133,178 first-time prescription redemptions for antidepressants and 23,077 first-time diagnoses of depression. The crude incidence rate of diagnosis of depression was 0.3/100 person-years with hormonal contraceptive use and 0.28/100 person-years with nonuse. Overall, there was an increased risk of diagnosis of depression associated with use of combination oral contraceptives (adjusted risk ratio [RR] 1.1, 95% CI 1.08-1.14), progestin-only oral contraceptives (adjusted RR 1.2, 95% CI 1.04-1.31), norgestrolmin/ethinylestradiol patch (adjusted RR 1.7, 95% CI 1.34-2.23), etonogestrel/ethinylestradiol vaginal ring (adjusted RR 1.6, 95% CI 1.45-1.77), and levonorgestrel intrauterine system (adjusted RR 1.4, 95% CI 1.22-1.5) compared to nonuse. Similar or higher estimates were obtained for incident antidepressant use.

This study found an association between hormonal contraceptive use and subsequent diagnosis of depression in adolescents and women and the risk of incident diagnosis of depression appeared to be greater with combination patch and vaginal ring products. Although the association between hormonal contraceptive use and incident diagnosis of depression was statistically significant, the absolute risk was small. A limitation to the study is that the results are potentially biased by the lack of controlling for the reasons why hormone therapy was begun and the reasons why the antidepressants were prescribed. Nonetheless, physicians need to be cognizant that depression is a potential side effect of hormonal contraception and should discuss this risk with their patients.

For more information, see the topics Oral contraceptives, Contraceptive patch and vaginal rings, and Intrauterine device (IUD) in DynaMed Plus. DynaMed users click here.