Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Medicine
Published in: BMC Medicine 1/2022

Open Access 01-12-2022 | Antidepressant Drugs | Research article

Use of hormonal contraceptives and antidepressants and risks of suicidal behavior and accidents among women with premenstrual disorders: a nationwide cohort study

Authors: Qian Yang, Tyra Lagerberg, Arvid Sjölander, Elizabeth R. Bertone-Johnson, Fang Fang, Weimin Ye, Zheng Chang, Unnur A. Valdimarsdóttir, Donghao Lu

Published in: BMC Medicine | Issue 1/2022

Login to get access

Abstract

Background

Women with premenstrual disorders (PMDs) are at increased risks of suicidal behavior and accidents. However, the effect of PMD first-line treatment on such risks have not been assessed.

Methods

To study the association between use of hormonal contraceptives or antidepressants and subsequent risks of suicidal behavior and accidents among women with PMDs. We conducted a nationwide register-based cohort study with between- and within-individual analyses in Sweden. All women with a clinical diagnosis/indication of PMDs recorded in the Patient Register and the Prescribed Drug Register during 1987–2011 were included (n = 23 029, age 15–52 years). Information on hormonal contraceptives and antidepressants prescribed for these women was obtained from the Prescribed Drug Register. Events of suicidal behavior (complete suicide and suicide attempt) and accidents were separately identified through the Patient and the Causes of Death Registers. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of suicidal behavior and accidents after use of hormonal contraceptives or antidepressants were estimated in between-individual and within-individual analyses (i.e., comparing the risk between use and no use in the same individual) using Poisson regression.

Results

Women with PMDs were followed for a median of 6.2 years. Compared to no use of hormonal contraceptives, use of hormonal contraceptives was associated with a lower risk of suicidal behavior in both between-individual (IRR 0.76, 0.43–1.34) and within-individual analyses (IRR 0.65, 0.51–0.83). These risk reductions were primarily restricted to combined products (IRR 0.18, 0.07–0.47 and 0.19, 0.08–0.42 in between- and within-individual analyses) and observed among women with/without psychiatric comorbidities (p for interaction 0.830 and 0.043 in between- and within-individual analyses). Yet, the use of hormonal contraceptives was not consistently associated with risk of accidents between between-individual (IRR 1.13, 1.01–1.27) and within-individual analyses (IRR 1.01, 0.92–1.11). Use of antidepressants was associated with a higher risk of suicidal behavior and accidents in both between- and within-individual analyses.

Conclusions

Our findings suggest that use of hormonal contraceptives, particularly combined products, is associated with reduced rates of suicidal behaviors, but not accidents, among women with PMDs. The estimates for antidepressants may be biased by indication.
Appendix
Available only for authorised users
Literature
1.
Yonkers KA, Simoni MK. Premenstrual disorders. Am J Obstet Gynecol. 2018;218(1):68–74.CrossRef
2.
3.
Association AP. Diagnostic and statistical manual of mental disorders (5th ed.)2013
4.
Halbreich U, Borenstein J, Pearlstein T, Kahn LS. The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD). Psychoneuroendocrinology. 2003;28(Suppl 3):1–23.
5.
Yang Q, Sjolander A, Li Y, Viktorin A, Bertone-Johnson ER, Ye W, et al. Clinical indications of premenstrual disorders and subsequent risk of injury: a population-based cohort study in Sweden. BMC Med. 2021;19(1):119.CrossRef
6.
Marjoribanks J, Brown J, O'Brien PM, Wyatt K. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev. 2013;2013(6):CD001396.
7.
Lopez LM, Kaptein AA, Helmerhorst FM. Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database Syst Rev. 2009(2):CD006586.
8.
Choi KH, Wang SM, Yeon B, Suh SY, Oh Y, Lee HK, et al. Risk and protective factors predicting multiple suicide attempts. Psychiatry Res. 2013;210(3):957–61.CrossRef
9.
Clarke S, Robertson I. A meta-analytic review of the Big Five personality factors and accident involvement in occupational and non-occupational settings. J Occup Organ Psychol. 2005;78(3):355–76. CrossRef
10.
Pilver CE, Libby DJ, Hoff RA. Premenstrual dysphoric disorder as a correlate of suicidal ideation, plans, and attempts among a nationally representative sample. Soc Psychiatry Psychiatr Epidemiol. 2013;48(3):437–46.CrossRef
11.
Bachmann S. Epidemiology of Suicide and the Psychiatric Perspective. Int J Environ Res Public Health. 2018;15(7).
12.
Steiner M, Steinberg S, Stewart D, Carter D, Berger C, Reid R, et al. Fluoxetine in the treatment of premenstrual dysphoria Canadian. Fluoxetine/Premenstrual Dysphoria Collaborative Study Group. N Engl J Med. 1995;332(23):1529–34.CrossRef
13.
Yonkers KA, Halbreich U, Freeman E, Brown C, Endicott J, Frank E, et al. Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual Dysphoric Collaborative Study Group. JAMA. 1997;278(12):983–8.CrossRef
14.
Yonkers KA, Brown C, Pearlstein TB, Foegh M, Sampson-Landers C, Rapkin A. Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstet Gynecol. 2005;106(3):492–501.CrossRef
15.
Pearlstein TB, Bachmann GA, Zacur HA, Yonkers KA. Treatment of premenstrual dysphoric disorder with a new drospirenone-containing oral contraceptive formulation. Contraception. 2005;72(6):414–21.CrossRef
16.
17.
Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.CrossRef
18.
Forslund T, Kosidou K, Wicks S, Dalman C. Trends in psychiatric diagnoses, medications and psychological therapies in a large Swedish region: a population-based study. BMC Psychiatry. 2020;20(1):328.CrossRef
19.
Wettermark B, Hammar N, Fored CM, Leimanis A, Otterblad Olausson P, Bergman U, et al. The new Swedish Prescribed Drug Register–opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiol Drug Saf. 2007;16(7):726–35.CrossRef
20.
Lu D, Aleknaviciute J, Bjarnason R, Tamimi RM, Valdimarsdottir UA, Bertone-Johnson ER. Pubertal development and risk of premenstrual disorders in young adulthood. Hum Reprod. 2021;36(2):455–64.CrossRef
21.
Kraemer GR, Kraemer RR. Premenstrual syndrome: diagnosis and treatment experiences. J Womens Health. 1998;7(7):893–907.CrossRef
22.
Lindgren GW, Degerfors IL, Fredriksson A, Loukili A, Mannerfeldt R, Nordin M, et al. Menarche 1990 in Stockholm schoolgirls. Acta Paediatr Scand. 1991;80(10):953–5.CrossRef
23.
Lindh-Astrand L, Hoffmann M, Jarvstrat L, Fredriksson M, Hammar M, Spetz Holm AC. Hormone therapy might be underutilized in women with early menopause. Hum Reprod. 2015;30(4):848–52.CrossRef
24.
Wu CH, Farley JF, Gaynes BN. The association between antidepressant dosage titration and medication adherence among patients with depression. Depress Anxiety. 2012;29(6):506–14.CrossRef
25.
Zhang L, Lagerberg T, Chen Q, Ghirardi L, D'Onofrio BM, Larsson H et al. Prediction of treatment dosage and duration from free-text prescriptions: an application to ADHD medications in the Swedish prescribed drug register. Evid Based Ment Health. 2021
26.
Kaplan S, Gurler M, Gonenc ILM. Relationship between fear of COVID-19 and premenstrual syndrome in Turkish university students. Women Health. 2022;62(7):644–54.CrossRef
27.
de Faire U, Friberg L, Lorich U, Lundman T. A validation of cause-of-death certification in 1,156 deaths. Acta Med Scand. 1976;200(3):223–8.
28.
Brooke HL, Talback M, Hornblad J, Johansson LA, Ludvigsson JF, Druid H, et al. The Swedish cause of death register. Eur J Epidemiol. 2017;32(9):765–73.CrossRef
29.
Clayton D, Hills M. Statistical models in epidemiology: OUP Oxford, 2013
30.
Gonzalez C, Dupuy J, López M, Luaces P, Marinello G, Vinagera E, Verdecia B, Crombet-Ramos T. CIMAvax®EGF vaccine therapy for non-small cell lung cancer: a weighted log-rank tests-based evaluation. Modern Chemother. 2013;2:6.CrossRef
31.
Campbell MJ, Machin D, and Walters SJ. Medical statistics: a textbook for the health sciences: Wiley, 2010
32.
Rothman KJ, Greenland S, and Lash TL. Modern epidemiology: Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. 2008
33.
Whitehead J. Fitting Cox’s Regression Model to Survival Data using GLIM. J Roy Stat Soc: Ser C (Appl Stat). 1980;29(3):268–75.
34.
Lichtenstein P, Halldner L, Zetterqvist J, Sjolander A, Serlachius E, Fazel S, et al. Medication for attention deficit-hyperactivity disorder and criminality. N Engl J Med. 2012;367(21):2006–14.CrossRef
35.
Lindberg M, Foldemo A, Josefsson A, Wirehn AB. Differences in prescription rates and odds ratios of antidepressant drugs in relation to individual hormonal contraceptives: a nationwide population-based study with age-specific analyses. Eur J Contracept Reprod Health Care. 2012;17(2):106–18.CrossRef
36.
Lee EW, Wei LJ, Amato DA, Leurgans S. Cox-type regression analysis for large numbers of small groups of correlated failure time observations. In: Klein J.P. GPK, editor. Survival Analysis: State of the Art Nato Science Series E: Applied Sciences. 211. Dordrecht: Springer; 1992
37.
Cascade EF, Kalali AH, Thase ME. Use of antidepressants: expansion beyond depression and anxiety. Psychiatry (Edgmont). 2007;4(12):25–8.
38.
Zhang L, Lagerberg T, Chen Q, Ghirardi L, D'Onofrio BM, Larsson H, et al. Prediction of treatment dosage and duration from free-text prescriptions: an application to ADHD medications in the Swedish prescribed drug register. Evid Based Ment Health. 2021;24(4):146-52.
39.
Osborn E, Brooks J, O’Brien PMS, Wittkowski A. Suicidality in women with premenstrual dysphoric disorder: a systematic literature review. Arch Womens Ment Health. 2021;24(2):173–84.CrossRef
40.
Eriksson E, Hedberg MA, Andersch B, Sundblad C. The serotonin reuptake inhibitor paroxetin is superior to the noradrenaline reuptake inhibitor maprotiline in the treatment of premenstrual syndrome. Neuropsychopharmacology. 1995;12(2):167–76.CrossRef
41.
Wyatt K, Dimmock P, Jones P, Obhrai M, O’Brien S. Efficacy of progesterone and progestogens in management of premenstrual syndrome: systematic review. BMJ. 2001;323(7316):776–80.CrossRef
42.
Moses-Kolko EL, Berga SL, Greer PJ, Smith G, Cidis Meltzer C, Drevets WC. Widespread increases of cortical serotonin type 2A receptor availability after hormone therapy in euthymic postmenopausal women. Fertil Steril. 2003;80(3):554–9.CrossRef
43.
Armstrong C. ACOG guidelines on noncontraceptive uses of hormonal contraceptives. Am Fam Physician. 2010;82(3):288.
44.
Ward KK, Roncancio AM, Plaxe SC. Women with gynecologic malignancies have a greater incidence of suicide than women with other cancer types. Suicide Life Threat Behav. 2013;43(1):109–15.CrossRef
45.
Adam Shapiro CLMK. Marital status and social well-being: are the married always better off? Soc Indic Res. 2007;88:17.
46.
Pearlstein T, Steiner M. Premenstrual dysphoric disorder: burden of illness and treatment update. J Psychiatry Neurosci. 2008;33(4):291–301.
47.
Polderman TJ, Benyamin B, de Leeuw CA, Sullivan PF, van Bochoven A, Visscher PM, et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet. 2015;47(7):702–9.CrossRef
48.
Santangelo AM, Ito M, Shiba Y, Clarke HF, Schut EH, Cockcroft G, et al. Novel primate model of serotonin transporter genetic polymorphisms associated with gene expression, anxiety and sensitivity to antidepressants. Neuropsychopharmacology. 2016;41(9):2366–76.CrossRef
49.
Forsberg L RH, Jacobsson A, Nyqvist K, Heurgren M. Kvalitet och innehåll i patientregistret. Utskrivningar från slutenvården 1964–2007 och besök i specialiserad öppenvård (exklusive primärvårdsbesök) 1997–2007. (Quality and content of the Patient Register)(2009–125–15). Kvalitet och innehåll i patientregistret Utskrivningar från slutenvården 1964–2007 och besök i specialiserad öppenvård (exklusive primärvårdsbesök) 1997–2007 (Quality and content of the Patient Register)(2009–125–15). Stockholm 2009
50.
Kendler KS, Maes HH, Sundquist K, Ohlsson H, Sundquist J. Genetic and family and community environmental effects on drug abuse in adolescence: a Swedish national twin and sibling study. Am J Psychiatry. 2014;171(2):209–17.CrossRef
51.
Fazel S, Langstrom N, Hjern A, Grann M, Lichtenstein P. Schizophrenia, substance abuse, and violent crime. JAMA. 2009;301(19):2016–23.CrossRef
52.
Sellgren C, Landen M, Lichtenstein P, Hultman CM, Langstrom N. Validity of bipolar disorder hospital discharge diagnoses: file review and multiple register linkage in Sweden. Acta Psychiatr Scand. 2011;124(6):447–53.CrossRef
53.
Ekholm B, Ekholm A, Adolfsson R, Vares M, Osby U, Sedvall GC, et al. Evaluation of diagnostic procedures in Swedish patients with schizophrenia and related psychoses. Nord J Psychiatry. 2005;59(6):457–64.CrossRef
54.
Ros HS, Cnattingius S, Lipworth L. Comparison of risk factors for preeclampsia and gestational hypertension in a population-based cohort study. Am J Epidemiol. 1998;147(11):1062–70.CrossRef
55.
Sanders SA, Graham CA, Bass JL, Bancroft J. A prospective study of the effects of oral contraceptives on sexuality and well-being and their relationship to discontinuation. Contraception. 2001;64(1):51–8.CrossRef
Metadata
Title
Use of hormonal contraceptives and antidepressants and risks of suicidal behavior and accidents among women with premenstrual disorders: a nationwide cohort study
Authors
Qian Yang
Tyra Lagerberg
Arvid Sjölander
Elizabeth R. Bertone-Johnson
Fang Fang
Weimin Ye
Zheng Chang
Unnur A. Valdimarsdóttir
Donghao Lu
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-022-02671-z

Other articles of this Issue 1/2022

BMC Medicine 1/2022 Go to the issue

Research article

Population-based cohort study: proton pump inhibitor use during pregnancy in Sweden and the risk of maternal and neonatal adverse events

Research article

Association of ideal cardiovascular health with cardiovascular events and risk advancement periods in a Mediterranean population-based cohort

Research article

Associations between cervical intraepithelial neoplasia during pregnancy, previous excisional treatment, cone-length and preterm delivery: a register-based study from western Sweden

Opinion

Non-invasive assessment of HFpEF in mouse models: current gaps and future directions

Research article

Cell-free DNA methylation markers for differential diagnosis of hepatocellular carcinoma

Research article

Rapid intrapartum test for maternal group B streptococcal colonisation and its effect on antibiotic use in labouring women with risk factors for early-onset neonatal infection (GBS2): cluster randomised trial with nested test accuracy study