Is use of hormonal contraception associated with treatment of depression?
In a nationwide prospective cohort study of more than 1 million women living in Denmark, an increased risk for first use of an antidepressant and first diagnosis of depression was found among users of different types of hormonal contraception, with the highest rates among adolescents.
Health care professionals should be aware of this relatively hitherto unnoticed adverse effect of hormonal contraception.
Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some women’s mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed.
To investigate whether the use of hormonal contraception is positively associated with subsequent use of antidepressants and a diagnosis of depression at a psychiatric hospital.
Design, Setting, and Participants
This nationwide prospective cohort study combined data from the National Prescription Register and the Psychiatric Central Research Register in Denmark. All women and adolescents aged 15 to 34 years who were living in Denmark were followed up from January 1, 2000, to December 2013, if they had no prior depression diagnosis, redeemed prescription for antidepressants, other major psychiatric diagnosis, cancer, venous thrombosis, or infertility treatment. Data were collected from January 1, 1995, to December 31, 2013, and analyzed from January 1, 2015, through April 1, 2016.
Use of different types of hormonal contraception.
Main Outcomes and Measures
With time-varying covariates, adjusted incidence rate ratios (RRs) were calculated for first use of an antidepressant and first diagnosis of depression at a psychiatric hospital.
A total of 1 061 997 women (mean [SD] age, 24.4 [0.001] years; mean [SD] follow-up, 6.4 [0.004] years) were included in the analysis. Compared with nonusers, users of combined oral contraceptives had an RR of first use of an antidepressant of 1.23 (95% CI, 1.22-1.25). Users of progestogen-only pills had an RR for first use of an antidepressant of 1.34 (95% CI, 1.27-1.40); users of a patch (norgestrolmin), 2.0 (95% CI, 1.76-2.18); users of a vaginal ring (etonogestrel), 1.6 (95% CI, 1.55-1.69); and users of a levonorgestrel intrauterine system, 1.4 (95% CI, 1.31-1.42). For depression diagnoses, similar or slightly lower estimates were found. The relative risks generally decreased with increasing age. Adolescents (age range, 15-19 years) using combined oral contraceptives had an RR of a first use of an antidepressant of 1.8 (95% CI, 1.75-1.84) and those using progestin-only pills, 2.2 (95% CI, 1.99-2.52). Six months after starting use of hormonal contraceptives, the RR of antidepressant use peaked at 1.4 (95% CI, 1.34-1.46). When the reference group was changed to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71).
Conclusions and Relevance
Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first diagnosis of depression, suggesting depression as a potential adverse effect of hormonal contraceptive use.
eFigure 1. Women and Person-years Fulfilling Various Inclusion and Exclusion Criteria
eFigure 2. Use of Different Types of Hormonal Contraceptives According to Age in Denmark 2013
eFigure 3. Use of Antidepressants in Users of Different Types of Hormonal Contraceptives Among Parous Women 15-34 Years Old
eTable 1. Included Groups of Hormonal Contraceptives and Corresponding Anatomic Therapeutic Chemical (ATC) Codes
eTable 2. Anatomic Therapeutic Chemical (ATC) Codes of the Included Antidepressants
eTable 3. Relative Risk of First Use of Antidepressants in Users of Different Types of Hormonal Contraceptives Compared With Users of Combined Oral Contraceptives With Levonorgestrel
eTable 4. Relative Risk of First Use of Antidepressants Compared With Never-Users of Hormonal Contraceptives
eTable 5. Relative Risk of First Use of Antidepressants in Starters of Different Types of Hormonal Contraceptives: Adolescents 15-19 Years of Age and Women 20-30 Years of Age
eTable 6. Overview of Articles on Hormonal Contraception and Depression
eDiscussion. Comparison With Prior Studies
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