Worly, B., Gur, T., & Schaffir, J. (2018). The relationship between progestin hormonal contraception and depression: a systematic review. Contraception, 97(6), 478-489. https://doi.org/10.1016/j.contraception.2018.01.010
Worly B, Gur T, Schaffir J. The relationship between progestin hormonal contraception and depression: a systematic review. Contraception. 2018;97(6):478-489. doi:10.1016/j.contraception.2018.01.010
Worly, Brett, et al. "The relationship between progestin hormonal contraception and depression: a systematic review." Contraception, vol. 97, no. 6, 2018, pp. 478-489.
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Abstract
Objective
We performed a systematic review to look for an association between progestin-only contraception and depression.
Methods
We searched PubMed, Ovid and Web of Science for English-language articles including progestin-only contraception and depression from database inception to September 2016. We evaluated study quality with the procedures guiding reviews for the United States Preventive Services Task Force and the Cochrane Risk of Bias Tools. We included studies that evaluated progestin-only contraception and depression, focusing on externally validated depression measures. We excluded case studies, review articles and other psychiatric disorders.
Results
We identified 26 studies that met the inclusion criteria, including 5 randomized controlled trials, 11 cohort studies and 10 cross-sectional studies. We found minimal association between progestin-only methods and depression. No correlation with depression was found in five low-quality, high-risk-of-bias progestin subdermal implant studies and four out of five varying-quality and medium-risk-of-bias levonorgestrel intrauterine device studies. Three medroxyprogesterone acetate intramuscular injection trials with varying levels of quality and bias show no difference in depression. Two progestin-only contraceptive pill studies with varying levels of quality and bias indicate no increase in depression scores, while one good-quality, medium-bias study shows an association between progestin-only pills, the intrauterine device and depression.
Conclusion
Despite perceptions in the community of increased depression following the initiation of progestin contraceptives, the preponderance of evidence does not support an association based on validated measures (mostly level II-1 evidence, moderate quality, low risk of bias).
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.
Young EA et al., 2007·Psychoneuroendocrinology·Free full text on PubMed Central
Hormone-based contraceptives affect mood in healthy women or in women with premenstrual dysphoric disorder (PMDD). No study has yet examined their association with mood in women with major depressive disorder (MDD). The purpose of this study was to determine whether estrogen-progestin combination or progestin-only contraceptives are associated with depression severity, function and quality of life, or general medical or psychiatric comorbidity in women with MDD. This analysis focused on a large population of female outpatients less than 40 years of age with non-psychotic MDD who were treated in 18 primary and 23 psychiatric care settings across the US, using data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Baseline demographic and clinical information was gathered and compared between three groups based on hormonal use: combination (estrogen-progestin)(N=232), progestin-only (N=58), and no hormone treatment (N=948). Caucasians were significantly more likely to use combined hormone contraception. Women on progestin-only had significantly more general medical comorbidities; greater hypersomnia, weight gain and gastrointestinal symptoms; and worse physical functioning than women in either of the other groups. Those on combined hormone contraception were significantly less depressed than those with no hormone treatment by the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated. The combined hormone group also demonstrated better physical functioning and less obsessive-compulsive disorder (COCD) comorbidity than either of the other groups. Synthetic estrogen and progestins may influence depressive and physical symptoms in depressed women.
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.
Keyes KM et al., 2013·Am J Epidemiol·Free full text on PubMed Central
An estimated 80% of sexually active young women in the United States use hormonal contraceptives during their reproductive years. Associations between hormonal contraceptive use and mood disturbances remain understudied, despite the hypothesis that estrogen and progesterone play a role in mood problems. In this study, we used data from 6,654 sexually active nonpregnant women across 4 waves of the National Longitudinal Study of Adolescent Health (1994-2008), focusing on women aged 25-34 years. Women were asked about hormonal contraceptive use in the context of a current sexual partnership; thus, contraceptive users were compared with other sexually active women who were using either nonhormonal contraception or no contraception. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. At ages 25-34 years, hormonal contraceptive users had lower mean levels of concurrent depressive symptoms (β = -1.04, 95% confidence interval: -1.73, -0.35) and were less likely to report a past-year suicide attempt (odds ratio = 0.37, 95% confidence interval: 0.14, 0.95) than women using low-efficacy contraception or no contraception, in models adjusted for propensity scores for hormonal contraceptive use. Longitudinal analyses indicated that associations between hormonal contraception and depressive symptoms were stable. Hormonal contraception may reduce levels of depressive symptoms among young women. Systematic investigation of exogenous hormones as a potential preventive factor in psychiatric epidemiology is warranted.
Khafagy GM et al., 2021·Korean J Fam Med·Free full text on PubMed Central
Contraceptive agents are widely used by women of reproductive age, and resulting depression is the most common side effect of this usage. This study aimed to study the effect of monthly injectable combined contraceptives versus that of combined oral contraceptive pills (COC) on patients' mood. A prospective cohort study was conducted on 124 females aged 18-45 years attending the Kom-Ashfeen Family Medicine Unit, El-Kalyubia, Egypt. Participants were divided into three groups according to their choice: group A included 44 participants who received monthly combined injectable contraceptives (CIC); group B included 40 participants who took COC; and group C included 40 participants who used the copper intrauterine device (IUD). The Patient Health Questionnaire-9 (PHQ-9) score was assessed at the beginning of the study and after 6 months of follow-up. After 6 months of follow-up, there were mild but statistically significant increases in the PHQ-9 score in groups A and B, with group A (CIC users) showing the highest increase. Approximately 34.1%, 27.5%, and 15% of CIC, COC, and IUD users, respectively, moved from the non-depression stage to mild depression after 6 months; this change was statistically significant in groups A and B only. Monthly injectable combined contraceptives and oral contraceptive pills were associated with an increased risk of developing mild depression; this risk was higher in users of CICs, although the difference was not statistically significant. Thus, it is crucial to counsel patients about this possible risk and to follow them up. However, further studies are required to confirm our results.
Contraception › Adverse Effects › Mood and Libido · Research Methods › Evidence Synthesis › Systematic Reviews
Jonathan Schaffir
Jon Schaffir, J Schaffir
PMID 29496297 29496297 DOI 10.1016/j.contraception.2018.01.010 10.1016/j.contraception.2018.01.010 Worly et al. 2018, Worly 2018
Cite this article
Worly, B., Gur, T., & Schaffir, J. (2018). The relationship between progestin hormonal contraception and depression: a systematic review. Contraception, 97(6), 478-489. https://doi.org/10.1016/j.contraception.2018.01.010
Worly B, Gur T, Schaffir J. The relationship between progestin hormonal contraception and depression: a systematic review. Contraception. 2018;97(6):478-489. doi:10.1016/j.contraception.2018.01.010
Worly, Brett, et al. "The relationship between progestin hormonal contraception and depression: a systematic review." Contraception, vol. 97, no. 6, 2018, pp. 478-489.
Keywords
Drug Implants, Progestins, Levonorgestrel, Medroxyprogesterone Acetate
