Risk of Depression due to Hormonal Contraception

The relationship between changes in mood and drive, or depressiveness, and the use of hormonal contraceptives has long been discussed and studied. Estrogens are thought to have more of an antidepressant effect, while progestins are more likely to have a mood-dampening effect.

Danish authors published a large, population-based, prospective cohort study that for the first time examined the association between hormonal contraceptive use and depression risk. Data from 1,061,997 women were included in the analysis (data from the Danish Sex Hormone Register Study). The mean follow-up was 6.4 years.

Compared with women not taking contraceptives, patients taking combined oral contraceptives (COCs) had a 1.23-fold risk of first antidepressant use (95% CI, 1.22-1.25).

The following is the risk of depression, ie, first use of an antidepressant, according to the form of hormonal contraceptive:

  • Users of progestin-only preparations had an increased risk of first antidepressant use of 1.34 (95% CI, 1.27-1.40)
  • Users of a levonorgestrel-containing intrauterine system of 1.4 (95% CI, 1.31-1.42).
  • Users of a vaginal ring (etonogestrel) of 1.6 (95% CI, 1.55-1.69).
  • Norgestrolmin patch user of 2.0 (95% CI, 1.76-2.18).

Similar or slightly lower estimates were found for depression diagnoses. Relative risk generally declined with increasing age.

Adolescents (ages, 15-19 years) using combined oral contraceptives had a risk increase for first antidepressant use of 1.8 (95% CI, 1.75-1.84) and those taking progestin pills (also called progestagens) had a risk increase of 2.2 (95% CI, 1.99 -2.52).

Six months after starting hormonal contraceptive use, the risk increase for antidepressant use reached 1.4 (95% CI, 1.34-1.46). In the reference group who never used hormonal contraceptives before, the odds of depression increased to 1.7 (95% CI, 1.66-1.71) after taking combined oral contraceptives.

CONCLUSION: Progestin-containing contraceptives are associated with increased odds of depression.

Further evidence

  • Hormonal contraception (“birth control pills,” etc.)-users versus women who never used hormonal contraceptives during the study period:
    • Suicide attempt 1.97-fold (95 percent confidence interval 1.85-2.10) more frequent.
    • 3.08-fold (1.34-7.08) more often completed suicide.
    • Strongest association two months after initiation of contraception.
    • Combined hormonal contraceptives (CHD; combination of estrogens and progestins) relative risk of 1.91 (1.79-2.03)
    • Monopreparations with progestin relative risk of 2.29 (1.77-2.95).
    • Vaginal rings (usually contain a progestin) relative risk of 2.58 (2.06-3.22)
    • Contraceptive patches (progestin product) relative risk of 3.28 (2.08-5.16).
  • Danish registry data: Evidence of doubled rate for suicide attempts, tripled rate for suicides:
    • The association was particularly pronounced among 15- to 19-year-olds and weakened somewhat among older women
    • Highest risk increase was calculated for progestin implants (4.4-fold) and medroxyprogesterone depot formulations (6.5-fold)(may be indication bias)