Association of Hormonal Contraception With Depression

Association of Hormonal Contraception

With Depression




JAMA Psychiatry published this nationwide prospective cohort study online on September 28, 2016.


Study Design:


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





  • n= 1 061 997 women.
  • mean [SD] age, 24.4 [0.001] years.
  • mean [SD] follow-up, 6.4 [0.004] years.

Compared with nonusers:

Compared with nonusers RR of first use of an antidepressant
Users of combined oral contraceptives 1.23 (95% CI, 1.22-1.25)
Users of progestogen-only pills 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)
Users of a levonorgestrel intrauterine system 1.4 (95% CI, 1.31-1.42)


The relative risks generally decreased with increasing age:

 Adolescents (age range, 15-19 years) using RR of a first use of an antidepressant
Combined oral contraceptives  1.8 (95% CI, 1.75-1.84)
 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).




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.


Likely Mechanism:


  • The addition of progesterone to hormone therapy has been shown to induce adverse mood effects in women.
  • The action of progesterone metabolites on the γ-aminobutyric acid A receptor complex, which is the major inhibitory system in the human central nervous system.
  • The external progestins, probably more than natural progesterone, increase levels of monoamine oxidase, which degrades serotonin concentrations and thus potentially produces depression and irritability.


Source: JAMA Psychiatry September 28, 2016.


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Dr. Harvinder Singh, M.D. (Admin)

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