By John McCarthy
Editor’s Note: As a FACTS elective student, John McCarthy wrote a research summary of “Association of Hormonal Contraception with Depression” by Charlotte Wessel Skovlund and colleagues. This large prospective cohort study examines the relationship between hormonal contraceptive use and depression. The findings demonstrate an association between hormonal contraceptives and increased risk of antidepressant use and first diagnosis of depression, with higher relative risks observed among adolescents and users of non-oral methods.
Through the FACTS elective, students are trained to critically evaluate research and explore the broader impact of hormones on women’s overall health, including their impact on mental health. FACTS also offers CME courses that expand clinicians’ understanding of the female cycle as a vital sign of health, including presentations that address mental health. This summary underscores the importance of informed, individualized counseling when discussing family-planning options.
Introduction
Diagnosed depression is a significant and rising concern for developing countries. Statistics show that women are at twice the risk of depression compared to men, and rates for women increase after puberty. [1] Previous literature has shown that hormones, particularly estrogen and progesterone, can negatively impact a woman’s mood. Additionally, mood symptoms are a known reason for cessation of hormonal birth control. [2] “Association of Hormonal Contraception with Depression” by Skovlund et al. investigated how different types of hormonal contraception were associated with the initiation of the treatment and first diagnosis of depression. [2]
Diagnosed depression is a significant and rising concern … (and) mood symptoms are a known reason for cessation of hormonal birth control.
Methodology
This prospective cohort study looked at all women between the ages of 15 and 34 living in Denmark between 1995 and 2013 who were treated with an antidepressant or those who had a first diagnosis of depression at an inpatient or outpatient psychiatric hospital. These women were identified for treatment or diagnosis by using the National Prescription Register and the Psychiatric Central Research Register, respectively. Women were excluded for a variety of reasons, including infertility, history of thrombotic events, history of cancer, immigrating individuals, or those who were pregnant or postpartum. Statistical analysis calculated the association between duration of hormonal contraceptive use and treatment of depression and initial diagnosis of depression—comparing users and non-users. [2] Adjustments were made based on age and trends in depression, education level, PCOS, endometriosis, smoking, and BMI.
Results
The study population included 1,061,997 women with 133,178 first antidepressant prescriptions and 23,077 first diagnoses of depression. Hormonal contraceptives—including combined oral contraceptives (RR=1.2), progestin-only pills (RR=1.3), transdermal patch (RR=2.0), vaginal ring (RR=1.5), implant (RR=2.1), levonorgestrel IUD (RR=1.4), and medroxyprogesterone depot shot (RR=2.7)—were linked to higher rates of first-time depression treatment. Rates for first-depression diagnosis were similar but slightly lower. [2]
Age-stratified analysis showed an overall increased relative risk (RR) across all ages that tended to decrease with age.[2] Notably, adolescents showed significantly higher rates of depression with combined oral contraceptives (RR=1.8), progestin-only pills (RR=2.2), and non-oral contraceptives (RR>3). [2]
Duration of contraceptive use showed a significant increase in RR for contraceptives used from two months to four years for the treatment of depression and the first diagnosis of depression. Rates peaked between three to six months around RR=1.4. [2]
Discussion
This study shows that commonly used methods of hormonal birth control are associated with an overall increased risk of treatment for depression and first diagnosis of depression compared to non-users. [2] This is particularly true for adolescents and young adults. The findings are consistent with the theory that progesterone is involved in the etiology of depression, as evidenced by higher rates with the transdermal patch, vaginal ring, and levonorgestrel IUD, compared to other routes of administration.
This study shows that commonly used methods of hormonal birth control are associated with an overall increased risk of treatment of depression and first diagnosis of depression … particularly for adolescents and young adults.
Strengths of this study include an incredibly large population size and information that was gathered without recall bias. Further, many important confounding variables, most notably age, were considered in the statistical analysis. Data from databases were analyzed based on daily information of hormonal contraceptive use. Additionally, the researchers found consistent results after they evaluated two distinct outcomes: new treatment of depression and new diagnosis of depression.
Hormonal contraception is known to increase the risk of depression, as noted on packaging, but research suggests this side effect may be underestimated. [2] In 2023, 1 in 10 U.S. adults took medication for depression, with women being twice as likely to be taking medication (15.3%) compared to men (7.4%). [3] While this study does not claim causation, the association between hormonal contraceptives and increased relative risk of depression is concerning. It’s worth taking into clinical consideration that there’s a 23% increased risk for all women who use oral combined contraceptives, an 80% increase for adolescents who use combined oral contraceptives, and a threefold increase for adolescents using non-oral hormonal contraceptives.[2]
While medical school training may emphasize how oral contraceptive pills (OCPs) and other hormonal methods of birth control increase a woman’s risk of breast cancer, cervical cancer, and blood clots, other negative effects, like depression, are often not discussed. In the FACTS elective, students study various fertility awareness-based methods (FABMs)—hormone-free methods to avoid pregnancy with effectiveness that matches or exceeds OCPs and other hormonal contraceptives. [4] [5] FABMs carry none of the risks, such as depression, and should be included in medical school education as safe and effective family-planning options.
While medical school training may emphasize how oral contraceptive pills (OCPs) and other hormonal methods of birth control increase a woman’s risk of breast cancer, cervical cancer, and blood clots, other negative effects, like depression, are often not discussed.
Additionally, FABMs can be utilized with medical management protocols, such as NeoFertility and NaProTECHNOLOGY to aid in the diagnosis and management of hormonal health dysfunction—often involving bioidentical progesterone. Unlike synthetic progestin in contraceptives, bioidentical progesterone may affect depression differently. Comparing depression rates between users of these forms would be a valuable study.
References
[1] Altemus M, Sarvaiya N, Epperson CN. Sex differences in anxiety and depression: clinical perspectives. Front Neuroendocrinol. 2014;35(3):320-330. doi:10.1016/j.yfrne.2014.05.004
[2] Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of hormonal contraception with depression. JAMA Psychiatry. 2016;73(11):1154-1162. doi:10.1001/jamapsychiatry.2016.2387
[3] Elgaddal N, Weeks JD, Mykyta L. Characteristics of adults aged 18 years and older who took prescription medication for depression: United States, 2023. NCHS Data Brief. 2025;(528):1-9. doi:10.15620/cdc/174589
[4] Bradley SEK, Polis CB, Micks EA, Steiner MJ. Effectiveness, safety, and comparative side effects. In: Cason P, Cwiak C, Edelman A, et al, eds. Contraceptive technology. 22nd ed. Jones & Bartlett Learning; 2023:130-131.
[5] Duane M, Stanford JB, Porucznik CA, Vigil P. Fertility awareness-based methods for women’s health and family planning. Front Med (Lausanne). 2022;9:858977. doi:10.3389/fmed.2022.858977
ABOUT THE AUTHOR
John McCarthy is currently a fourth-year medical student at Creighton University School of Medicine in Omaha, NE. He completed his undergraduate years and Master of Education at The University of Notre Dame in South Bend, IN. In July, he will be headed back to South Bend where he will be starting his family medicine residency at Memorial Hospital. He is particularly interested in obstetrics and fertility care as a future family medicine doctor. He enrolled in the FACTS elective to gain a better understanding of natural family-planning methods so he can offer natural alternatives instead of medical contraceptives, more holistically care for women in their fertility, and better diagnose and treat their medical conditions.
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