We commonly receive questions regarding the potential effects of oral contraceptives (birth control pills) on mood and risk for depression. Despite the prevalence of OC usage, few studies have explored the association between hormonal contraceptive use and mood disturbance. According to a large Danish study of more than one million young women, the use of hormonal contraception (including oral, transdermal, vaginal and intrauterine forms) may lead to a small but statistically significant increase in risk for depression.
This was a nationwide prospective cohort study utilizing data from the National Prescription Register and the Psychiatric Central Research Register in Denmark. All women aged 15 to 34 years; women were excluded if they had a history of major psychiatric diagnosis, including depression, or if they had previously filled a prescription for an antidepressant.
A total of 1,061,997 women (mean age, 24.4 years; mean follow-up, 6.4 years) were included in the analysis. Compared with nonusers, users of hormonal contraception had a small but statistically significant increase in first use of an antidepressant, with relative risk (RR) varying according to type of contraception:
- Combined oral contraceptives: RR 1.23 (95% CI, 1.22-1.25)
- Progestogen-only pills: RR 1.34 (95% CI, 1.27-1.40)
- Patch (norelgestromin): RR 2.0 (95% CI, 1.76-2.18)
- Vaginal ring (etonogestrel): RR 1.6 (95% CI, 1.55-1.69)
- Levonorgestrel intrauterine system, 1.4 (95% CI, 1.31-1.42).
With regard to a new diagnosis of depression, similar or slightly lower estimates or risk were observed. The relative risks generally decreased with increasing age. Adolescents (age range, 15-19 years) using combined oral contraceptives had an RR of first use of an antidepressant of 1.8 (95% CI, 1.75-1.84) and the risk was higher in those using progestin-only pills, 2.2 (95% CI, 1.99-2.52).
The real strength of this study is its size, which has allowed the researchers to conduct an adequately powered analysis and to appreciate differences between different types of hormonal contraceptives. The other notable strength of this study was that it followed women longitudinally, folding them into the study before the onset of depression. (That said, it would have been helpful to have another arm of the study looking at risk for depression in women with histories of depression.)
There are some interesting findings. While the relative risk for depression increased in all age groups using hormonal contraception, it appears that adolescent girls were the most vulnerable. While this finding may indicate that adolescent girls possess a heightened sensitivity to hormones, it could be that in the older group, the women most vulnerable to depression had already experienced an episode of depression and therefore were not included in this study.
It was also surprising to find that vaginal and intrauterine hormonal contraceptives were also associated with an increased risk of depression. Much lower levels are released by these forms of contraception; however, these data suggest that enough hormone is released to have an impact on vulnerability to depression. This is consistent with our clinical observation that some women experience mood changes after insertion of the levonorgestrel-releasing intrauterine device (Mirena).
How Will This Study Affect Use of Hormonal Contraception?
While this study has the statistical power to indicate that hormonal contraception may increase risk for depression, it is a relatively small increase in risk. In a commentary published in Psychiatry News, experts urge caution in responding to these new data, stating “the findings should not result in precipitate action by patients or their physicians. While the effects are significant, clinicians must compare them to what could happen if women were not on hormonal contraceptives.”
While this study focused on the effects of hormonal contraception on women with no history of psychiatric illness, we must also consider the impact of hormonal contraception on mood in women with histories of depression.
One of the largest studies included 6,654 sexually active non-pregnant women participating in the National Longitudinal Study of Adolescent Health. In a cohort of women aged 25–34 years, the researchers compared contraceptive users with other sexually active women who were using either non-hormonal contraception or no contraception. Users of hormonal contraceptives had lower mean levels of depressive symptoms and were less likely to have attempted suicide in the previous year (odds ratio = 0.37, 95% confidence interval: 0.14, 0.95) than women using other forms of contraception or no contraception.
In the Harvard Study of Moods and Cycles, it was found that women with histories of depression were more likely to experience premenstrual mood worsening on oral contraceptives than women with no history of depression. However, most women with a history of depression experienced either no change in their mood (61%) or mood improvement (14%); only a small number (25%) experienced mood worsening on oral contraceptives.
Before starting hormonal contraception, women should talk to their clinicians about their history of depression. Those with a history of depression should be attentive to potential mood changes after starting a hormonal contraceptive; however, these studies taken together indicate that hormonal contraceptives continue to be a viable option for contraception for all women, including those with a history of depression.
Ruta Nonacs, MD PhD
Joffe H, Cohen LS, Harlow BL. Impact of oral contraceptive pill use on premenstrual mood: Predictors of improvement and deterioration. Am J Obstet Gynecol 2003;189:1523-30.
Keys KM, Cheslack-Postava K, Westhoff C, et al. Association of Hormonal Contraceptive Use With Reduced Levels of Depressive Symptoms: A National Study of Sexually Active Women in the United States. Am J Epidemiol 2013.
Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of Hormonal Contraception With Depression. JAMA Psychiatry. 2016 Sep 28. [Epub ahead of print]
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