Hormonal sensitivity may contribute to the risk of depression in some women, as observed during the premenstrual, postpartum, and perimenopausal phases, and when initiating hormonal contraception (HC). However, little evidence exists to support that such depressive episodes are linked across the reproductive life span.
Objective
To determine whether prior depression associated with HC initiation is coupled with a higher risk of postpartum depression (PPD) than prior depression not associated with HC initiation. DESIGN, SETTING, AND
Participants
This cohort study used Danish health registry data collected from January 1, 1995, through December 31, 2017, and analyzed from March 1, 2021, through January 1, 2023. All women living in Denmark born after 1978 with their first delivery between January 1, 1996, and June 30, 2017, were eligible for inclusion; 269 354 met these criteria. Women were then excluded if they had never used HC or if they had a depressive episode before 1996 or within 12 months prior to delivery.
Exposures: Prior depression associated with vs not associated with HC initiation, ie, if developed within 6 months after start of an HC exposure or not. Depression was defined as a hospital diagnosis of depression or filling a prescription for antidepressant medication.
MAIN OUTCOMES AND
Measures
Crude and adjusted odds ratios (ORs) were calculated for the incidence of PPD defined as the development of depression within 6 months after first delivery.
Results
Of 188 648 first-time mothers, 5722 (3.0%) (mean [SD] age, 26.7 [3.9] years) had a history of depression associated with initiation of HC use, and 18 431 (9.8%) (mean [SD] age, 27.1 [3.8] years) had a history of depression not associated with the initiation of HC. Women with HC-associated depression had a higher risk of PPD than women with prior non-HC-associated depression (crude OR, 1.42 [95% CI, 1.24-1.64]; adjusted OR, 1.35 [95% CI, 1.17-1.56]).
Conclusions and Relevance: These findings suggest that a history of HC-associated depression may be associated with a higher risk of PPD, supporting that HC-associated depression may indicate PPD susceptibility. This finding offers a novel strategy in clinical PPD risk stratification and points to the existence of a hormone-sensitive subgroup of women.
PMID 37099310 37099310 DOI 10.1001/jamapsychiatry.2023.0807 10.1001/jamapsychiatry.2023.0807 Larsen et al. 2023, Larsen 2023
Cite this article
Larsen, S. V., Mikkelsen, A. P., Lidegaard Ø, & Frokjaer, V. G. (2023). Depression Associated With Hormonal Contraceptive Use as a Risk Indicator for Postpartum Depression. JAMA psychiatry, 80(7), 682-689. https://doi.org/10.1001/jamapsychiatry.2023.0807
Larsen SV, Mikkelsen AP, Lidegaard Ø, Frokjaer VG. Depression Associated With Hormonal Contraceptive Use as a Risk Indicator for Postpartum Depression. JAMA Psychiatry. 2023;80(7):682-689. doi:10.1001/jamapsychiatry.2023.0807
Larsen, S. V., et al. "Depression Associated With Hormonal Contraceptive Use as a Risk Indicator for Postpartum Depression." JAMA psychiatry, vol. 80, no. 7, 2023, pp. 682-689.
Studies have demonstrated an association between hormonal contraception use with subsequent depression and antidepressant use. This association has not been assessed among postpartum women. This study is a secondary analysis of insurance records from 75,528 postpartum women enrolled in the US military medical system, who delivered between October 2012 and September 2014. Our analyses excluded women who used antidepressants or had a diagnosis of depression in the 24months prior to delivery. We assessed the relationship of hormonal contraception use with subsequent antidepressant use or diagnosis with depression in the first 12months postpartum using Cox proportional hazards regression, with a time dependent covariate measuring exposure to hormonal contraception. Antidepressants were prescribed to 7.8% of women and 5.0% were diagnosed with depression. In multivariable analysis adjusting for demographics, both antidepressant use and diagnosis with depression were associated with: younger age, lower socioeconomic status, and a history of military service. Compared to women with no hormonal contraceptive use, use of etonogestrel containing contraception was associated with a higher risk of antidepressant use (Implant: adjHR:1.22(95%CI:1.06-1.41), p<0.001; Ring:1.45(1.16-1.80), p=0.001). Use of norethindrone-only pills was associated with a lower risk of antidepressant use (0.58(0.52-0.64), p<0.001) and depression diagnosis (0.56(0.49-0.64), p<0.001). Use of a levonorgestrel intrauterine system was associated with a lower risk of depression diagnoses (0.65(0.52-0.82), p<0.001). The risk of major depression diagnosis and antidepressant use in the postpartum period varies with the type of hormonal contraception used. Further research is required to describe the mechanisms of these relationships.
Singata-Madliki M et al., 2016·J Fam Plann Reprod Health Care
Depot medroxyprogesterone acetate (DMPA) is the most commonly used hormonal contraceptive method in South Africa. It is frequently administered in the immediate postnatal period, yet it is unclear whether it affects the risk of postnatal depression (PND). To determine whether DMPA increases the risk of PND compared with the copper-containing intrauterine device (IUD) when administered after delivery. DESIGN AND A single-blind randomised controlled trial conducted at two teaching hospitals in East London, South Africa. Eligible, consenting women (N=242) requiring postnatal contraception were randomised to receive DMPA or an IUD within 48 hours of childbirth and interviewed at 1 and 3 months postpartum. Depression was measured using the Beck Depression Inventory (BDI-II) and the Edinburgh Postnatal Depression Scale (EPDS). Resumption of sexual intercourse, menstrual symptoms and breastfeeding rates were also assessed. One-month EPDS depression scores were statistically significantly higher in the DMPA arm compared with IUD arm (p=0.04). Three-month BDI-II scores were significantly higher in the DMPA arm than in the IUD arm (p=0.002) and, according to the BDI-II but not the EPDS, more women in the DMPA arm had major depression at this time-point (8 vs 2; p=0.05). There were no statistically significant differences in other outcome measures except that fewer women had resumed sexual activity by 1 month postpartum in the DMPA arm (13% vs 26%; p=0.02). The possibility that immediate postnatal DMPA use is associated with depression cannot be excluded. These findings justify further research with longer follow-up. PACTR201209000419241.
Depot medroxyprogesterone acetate (DMPA) is commonly prescribed to women immediately postpartum due to its efficacy, convenience and lack of estrogen. It is unclear whether administering a progestin injection can affect the course of postpartum depression (PPD), which some suspect to be influenced by hormonal changes. In this retrospective study, the objective was to determine whether DMPA administered immediately postpartum influences the development of PPD. A retrospective review of a total of 404 charts was conducted of clinic patients who were scheduled for 6-week postpartum visits at a major medical center, where all patients are routinely asked to complete the Edinburgh Postnatal Depression Scale (EPDS). The average scores on the EPDS at these visits were compared between patients who had received DMPA prior to postpartum discharge from the hospital and patients who had not received any hormonal contraception by using an unpaired t test. In addition, the proportions of women diagnosed with PPD via the scale were compared via contingency tables. Fifty-five women who had received immediate DMPA were compared with 192 women with no hormonal contraception after delivery. The groups were similar in parity, race, mode of delivery and weight, but women receiving DMPA were significantly younger (24.2 vs. 26.2 years, p=.03). Mean EPDS scores at 6 weeks postpartum were not statistically significant between the groups (5.02 vs. 6.17, p=.16). Six patients (10.9%) who received immediate DMPA were diagnosed with PPD based on EPDS scores greater than or equal to 13, while 27 (14.1%) in the comparison group had PPD (p=.88). Administration of DMPA in the immediate postpartum period does not appear to predispose women to PPD.
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, 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. Exposures: 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). 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.