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Is Postpartum Depression More Common in Women with Sensitivity to Hormonal Contraceptive?

Women are about twice as likely as men to experience a serious depressive episode. Because this gender gap emerges in adolescence and persists until menopause, we speculate that some women are more vulnerable than others to the reproductive hormonal shifts that happen in the course of the course of a lady’s reproductive life. Increased vulnerability to depression coincides with the premenstrual phase of the menstrual cycle, where about 5% of ladies experience premenstrual dysphoric disorder (PMDD), the postpartum period, and through perimenopause. 



One other subgroup of ladies with hormonal sensitivity are women who experience mood changes or depressive symptoms after initiating treatment with a hormonal contraceptive. Many have speculated that ladies with sensitivity to hormonal contraceptives could also be more vulnerable to depression at other times of hormonal transition, including the postpartum period. While the hypothesis that ladies with sensitivity to hormonal contraceptives may be more vulnerable to postpartum depression is definitely plausible, it has not been fastidiously studied.

To find out whether prior depression related to hormonal contraception is a risk factor for PPD, a recent study analyzed data from the Danish health registry, a cohort including 269,354 first-time moms. Women were excluded in the event that they had never used hormonal contraception or in the event that they had a depressive episode inside the 12 months prior to delivery. Cases of postpartum depression were defined because the filling a prescription for antidepressant medication or receiving a hospital discharge diagnosis of depression inside 6 months of childbirth.

On this cohort of 188,648 first-time moms:

  • 5722 (3.0%; mean [SD] age, 26.7 [3.9] years) had a history of HC-associated depression 
  • 18 431 (9.8%; mean [SD] age, 27.1 [3.8] years) had a history of non-HC-associated depression 
  • 2457 women developed PPD, corresponding to an incidence rate of 1.3%
  • Women with HC-associated depression had a better risk of PPD than women with prior non-HC-associated depression (adjusted OR, 1.35 [95% CI, 1.17-1.56]).

Vital Note: This study looks only at women who received pharmacologic treatment or were hospitalized for PPD. Thus, rates of identified PPD on this study are low in comparison with other studies that use questionnaires, corresponding to the EPDS, to discover women with PPD. Cases of PPD on this study more than likely represent only women with greater severity of depressive symptoms. 

Some Other Interesting Findings

The researchers observed that women with HC-associated depression had more depressive episodes than women with non–HC-associated depression; 63.4% of the ladies with HC-associated depression had a couple of episode of depression, in comparison with 38.6% of the ladies with non-HC-associated depression. Future studies are needed to find out whether there could also be other clinical or demographic variables which distinguish women with HC-associated depression from those with non–HC-associated depression.

Although this study shows that having a history of HC-associated depression appears to be a risk factor for PPD, the danger related to non-HC-associated episodes of depression can also be very high, when put next to the magnitude of risk observed in women with no history of depression (See Figure 2, above). Put more succinctly, risk for PPD in women with no history of depression was about 0.9% on this study. In women with a history of any type of depressive episode (related to HC or not), risk for PPD increases to 4.0%. That represents a couple of 4.4-fold increased risk for PPD. If depression was related to HC use, the danger for PPD was 5.8-fold higher than observed in women with no history. If depression was not related to HC use, the danger for PPD was about 4.1-fold higher. Thus, history of depression represents one among our strongest predictors of risk for PPD.

Clinical Implications

The findings of this study suggest that a history of depression related to the usage of hormonal contraception could also be a risk factor for PPD, supporting the hypothesis that some women are uniquely vulnerable to reproductive hormonal shifts and thus could also be more vulnerable to depression at times related to shifts within the reproductive hormonal milieu. While it is smart to ask if a lady has had an episode of depression related to the usage of hormonal contraceptives, women who’ve had episodes of depression not related to the usage of hormonal contraceptives even have a high risk of developing PPD.

Because this study defined PPD because the filling a prescription for antidepressant medication or receiving a hospital discharge diagnosis of depression inside 6 months of childbirth, this study focused on the prevalence of more severe episodes of PPD. Further study is indicated to higher understand the link between HC-associated mood changes and risk for milder types of depression. 

Ruta Nonacs, MD PhD

References

Larsen SV, Mikkelsen AP, Lidegaard Ø, Frokjaer VG. Depression Associated With Hormonal Contraceptive Use as a Risk Indicator for Postpartum Depression. JAMA Psychiatry. 2023 Jul 1;80(7):682-689. 

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