Review of: Skovlund CW et al, Am J Psychiatry 2017 Nov 17 appiajp201717060616. [Epub ahead of print]

Clinical evidence is growing regarding an association between hormonal contraception and mood disturbances (Skovlund CW et al, JAMA Psychiatry 2016;73(11):1154–1162), and recently researchers at the University of Copenhagen published a study attempting to correlate hormonal contraceptive use with suicidal thinking and behavior.

From 1996 through 2013, a nationwide prospective cohort study was conducted of women in Denmark with no psychiatric diagnoses, no antidepressant use, and no hormonal contraceptive use prior to age 15. A total of 475,802 women were followed for an average of 8.3 years. Their ages ranged from 15 to 33 (with an average age of 21), and 54% of them were current or recent users of hormonal contraception.

During this same time period, there were 6,999 first suicide attempts and 71 suicides in this population. The risks for suicide attempt and suicide were calculated by comparing women who used hormonal contraception vs those who did not. The relative risk among current and recent users of hormonal contraception was 1.97 for first suicide attempt and 3.08 for completed suicide. All hormonal contraceptive products were considered in the study: patches, vaginal rings, IUDs, depot formulations, progestin-only products, and oral combined products.

Stratified by age, the relative risk of suicide attempt with hormonal contraceptive use was 2.06 for women ages 15–19, 1.61 for ages 20–24, and 1.65 for ages 25–33. Also, the relative risk for a first suicide attempt increased rapidly after initiation of hormonal contraceptive use, peaking after 2 months, and then remaining at least double its initial value until 1 year after initiation.

Stratified by various classes of hormonal contraception products, the relative risks for suicide attempt were 1.91 for oral combined products, 2.29 for oral progestin-only products, 2.58 for the vaginal ring, and 3.28 for the patch.

TCPR’s Take
Suicide and suicide attempts are rare events; however, the enormity of the study population in this analysis allowed for impressive statistical rigor. Also, as mood symptoms are a common reason to stop hormonal contraception use, this study skillfully avoided any such out-selection by including all women prior to their first use of any hormonal contraception.

The results of this study support the hypothesis that hormonal contraception may have a direct influence on the neurobiology of suicidal behavior. Though rare, even with elevated relative risks, these potential side effects of hormonal contraceptive use are clearly significant, and so TCPR recommends informing patients using hormonal contraceptives about these risks. Also, we should observe particular caution in any of our adolescent patients starting oral contraceptives for the first time.