Hormonal contraception use is common among human immunodeficiency virus (HIV)-infected women. Risk of psychiatric and other noninfectious complications of hormonal contraception use has not been described in this population.
Methods:
We performed a retrospective cohort study of HIV-infected women receiving care in Tennessee from 1998 to 2008 to examine the risks of incident psychiatric and other noncommunicable diseases (NCDs), including cardiovascular, hepatic, renal, and malignant diseases, and hormonal contraception use, including depot medroxyprogesterone acetate (DMPA) and combined estrogen- and progestin-containing hormonal contraceptives. We used marginal structural models with inverse probability weights to account for time-varying confounders associated with hormonal contraception use.
Results:
Of the 392 women included, 94 (24%) used hormonal contraception during the study period. Baseline psychiatric disease was similar between women who received and did not receive hormonal contraception. There were 69 incident psychiatric diagnoses and 72 NCDs. Only time-varying DMPA use was associated with increased risk of psychiatric disease (adjusted odds ratio [aOR] 3.70; 95% confidence interval [95% CI] 1.32–10.4) and mood disorders, specifically (aOR 4.70 [1.87–11.8]). Time-varying and cumulative combined hormonal contraception use were not statistically associated with other NCDs (aOR 1.64, 95% CI 0.64–4.12 and aOR 1.16, 95% CI 0.86–1.56, respectively). However, risk of incident NCDs was increased with cumulative DMPA exposure (per year exposure aOR 1.45, 95% CI 1.01–2.08).
Conclusions:
Among HIV-infected women, DMPA was associated with risk of incident psychiatric diseases, particularly mood disorders, during periods of use. Cumulative DMPA exposure was also associated with risk of other NCDs. However, combined estrogen and progestin-containing hormonal contraception use was not statistically associated with risk of any NCDs.
Get full access to this article
View all access options for this article.
References
1.
ReynoldsHW, SteinerMJ, CatesWJr.Contraception's proved potential to fight HIV. Sex Transm Infect, 2005; 81:184–185.
2.
United Nations Department of Economic and Social Affairs. World Contraceptive Use 2011. United Nations, 2011. Available at: www.un.org/esa/population/publications/contraceptive2011/contraceptive2011.htm Accessed November16, 2014.
3.
SunM, PeipertJF, ZhaoQ, et al.Trends in contraceptive use among women with human immunodeficiency virus. Obstet Gynecol, 2012; 120:783–790.
4.
BaetenJM, BenkiS, ChohanV, et al.Hormonal contraceptive use, herpes simplex virus infection, and risk of HIV-1 acquisition among Kenyan women. AIDS, 2007; 21:1771–1777.
5.
LavreysL, BaetenJM, MartinHLJr, et al.Hormonal contraception and risk of HIV-1 acquisition: Results of a 10-year prospective study. AIDS, 2004; 18:695–697.
6.
MorrisonCS, ChenPL, KwokC, et al.Hormonal contraception and HIV acquisition: Reanalysis using marginal structural modeling. AIDS, 2010; 24:1778–1781.
7.
MorrisonCS, RichardsonBA, MmiroF, et al.Hormonal contraception and the risk of HIV acquisition. AIDS, 2007; 21:85–95.
8.
MartinHLJr., NyangePM, RichardsonBA, et al.Hormonal contraception, sexually transmitted diseases, and risk of heterosexual transmission of human immunodeficiency virus type 1. J Infect Dis, 1998; 178:1053–1059.
9.
HeffronR, DonnellD, ReesH, et al.Use of hormonal contraceptives and risk of HIV-1 transmission: A prospective cohort study. Lancet Infect Dis, 2012; 12:19–26.
10.
PolisCB, CurtisKM. Use of hormonal contraceptives and HIV acquisition in women: A systematic review of the epidemiological evidence. Lancet Infect Dis, 2013; 13:797–808.
11.
CejtinHE, JacobsonL, SpringerG, et al.Effect of hormonal contraceptive use on plasma HIV-1-RNA levels among HIV-infected women. AIDS, 2003; 17:1702–1704.
12.
MorrisonCS, DemersK, KwokC, et al.Plasma and cervical viral loads among Ugandan and Zimbabwean women during acute and early HIV-1 infection. AIDS, 2010; 24:573–582.
13.
PolisCB, GrayRH, BwanikaJB, et al.Effect of hormonal contraceptive use before HIV seroconversion on viral load setpoint among women in Rakai, Uganda. J Acquir Immune Defic Syndr, 2011; 56:125–130.
14.
RichardsonBA, OtienoPA, Mbori-NgachaD, OverbaughJ, FarquharC, John-StewartGC. Hormonal contraception and HIV-1 disease progression among postpartum Kenyan women. AIDS, 2007; 21:749–753.
15.
StringerEM, GigantiM, CarterRJ, El-SadrW, AbramsEJ, StringerJS. Hormonal contraception and HIV disease progression: A multicountry cohort analysis of the MTCT-Plus Initiative. AIDS, 2009; 23:S69–S77.
16.
MorrisonCSP, ChenP-LP, NankyaIMDP, et al.Hormonal contraceptive use and HIV disease progression among women in Uganda and Zimbabwe. J Acquir Immune Defic Syndr, 2011; 57:157–164.
17.
PolisCB, WawerMJ, KiwanukaN, et al.Effect of hormonal contraceptive use on HIV progression in female HIV seroconverters in Rakai, Uganda. AIDS, 2010; 24:1937–1944.
18.
PhillipsSJ, CurtisKM, PolisCB. Effect of hormonal contraceptive methods on HIV disease progression: A systematic review. AIDS, 2013; 27:787–794.
19.
LidegaardO, LokkegaardE, JensenA, SkovlundCW, KeidingN. Thrombotic stroke and myocardial infarction with hormonal contraception. New Engl J Med, 2012; 366:2257–2266.
20.
Chasan-TaberL, StampferMJ. Epidemiology of oral contraceptives and cardiovascular disease. Ann Intern Med, 1998; 128:467–477.
21.
LidegaardO, LokkegaardE, SvendsenAL, AggerC. Hormonal contraception and risk of venous thromboembolism: National follow-up study. BMJ, 2009; 339:b2890.
22.
SidneyS, CheethamTC, ConnellFA, et al.Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users. Contraception, 2013; 87:93–100.
23.
GreenlundKJ, WebberLS, SrinivasanS, WattigneyW, JohnsonC, BerensonGS. Associations of oral contraceptive use with serum lipids and lipoproteins in young women: The Bogalusa Heart Study. Ann Epidemiol, 1997; 7:561–567.
LopezLM, ChenM, MullinsS, CurtisKM, HelmerhorstFM. Steroidal contraceptives and bone fractures in women: Evidence from observational studies. Cochrane Database Syst Rev, 2012; 8:CD009849.
27.
BottcherB, RadenbachK, WildtL, HinneyB. Hormonal contraception and depression: A survey of the present state of knowledge. Arch Gynecol Obstet, 2012; 286:231–236.
28.
CivicD, ScholesD, IchikawaL, et al.Depressive symptoms in users and non-users of depot medroxyprogesterone acetate. Contraception, 2000; 61:385–390.
29.
ToffolE, HeikinheimoO, KoponenP, LuotoR, PartonenT. Further evidence for lack of negative associations between hormonal contraception and mental health. Contraception, 2012; 86:470–480.
30.
TsaiR, SchaffirJ. Effect of depot medroxyprogesterone acetate on postpartum depression. Contraception, 2010; 82:174–177.
31.
WesthoffC, WielandD, TiezziL. Depression in users of depo-medroxyprogesterone acetate. Contraception, 1995; 51:351–354.
32.
Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996–2006: Collaborative analysis of 13 HIV cohort studies. Clin Infect Dis, 2010; 50:1387–1396.
33.
WesterCW, KoetheJR, ShepherdBE, et al.Non-AIDS-defining events among HIV-1-infected adults receiving combination antiretroviral therapy in resource-replete versus resource-limited urban setting. AIDS, 2011; 25:1471–1479.
34.
PalellaFJJr., BakerRK, MoormanAC, et al.Mortality in the highly active antiretroviral therapy era: Changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr, 2006; 43:27–34.
35.
AnisAH, NosykB, SunH, et al.Quality of life of patients with advanced HIV/AIDS: Measuring the impact of both AIDS-defining events and non-AIDS serious adverse events. J Acquir Immune Defic Syndr, 2009; 51:631–639.
36.
FreibergMS, ChangCC, SkandersonM, et al.The risk of incident coronary heart disease among veterans with and without HIV and hepatitis C. Circulation, 2011; 4:425–432.
37.
EngelsEA, BiggarRJ, HallHI, et al.Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer, 2008; 123:187–194.
38.
CraneM, IserD, LewinSR. Human immunodeficiency virus infection and the liver. World J Hepatol, 2012; 4:91–98.
39.
NadkarniGN, KonstantinidisI, WyattCM. HIV and the aging kidney. Curr Opin HIV AIDS, 2014; 9:340–345.
40.
CalvoM, MartinezE. Update on metabolic issues in HIV patients. Curr Opin HIV AIDS, 2014; 9:332–339.
HearpsAC, MartinGE, RajasuriarR, CroweSM. Inflammatory co-morbidities in HIV+ individuals: Learning lessons from healthy ageing. Curr HIV/AIDS Rep, 2014; 11:20–34.
43.
SchuellerPO, FeuringM, SharkovaY, GrimmW, ChristM. Effects of synthetic progestagens on autonomic tone, neurohormones and C-reactive protein levels in young healthy females in reproductive age. Int J Cardiol, 2006; 111:42–48.
44.
AuerbachL, HafnerT, HuberJC, PanzerS. Influence of low-dose oral contraception on peripheral blood lymphocyte subsets at particular phases of the hormonal cycle. Fertil Steril, 2002; 78:83–89.
45.
GerretsenG, KremerJ, NaterJP, BleuminkE, de GastGC, TheTH. Immune reactivity of women on hormonal contraceptives: Dinitrochlorobenzene sensitization test and skin reactivity to irritants. Contraception, 1979; 19:83–89.
46.
HuijbregtsRP, HeltonES, MichelKG, et al.Hormonal contraception and HIV-1 infection: Medroxyprogesterone acetate suppresses innate and adaptive immune mechanisms. Endocrinology, 2013; 154:1282–1295.
47.
AljassemK, RaboudJM, HartTA, et al.Gender differences in severity and correlates of depression symptoms in people living with HIV in Ontario, Canada. J Int Assoc Provid AIDS Care, 2014; Jun4: 2325957414536228. [Epub ahead of print].
48.
MelloVA, MalbergierA. Depression in women infected with HIV. Revista Bras Psiquiatr, 2006; 28:10–17.
49.
MelloVA, SeguradoAA, MalbergierA. Depression in women living with HIV: Clinical and psychosocial correlates. Arch Womens Ment Health, 2010; 13:193–199.
50.
AnastosK, SchneiderMF, GangeSJ, et al.The association of race, sociodemographic, and behavioral characteristics with response to highly active antiretroviral therapy in women. J Acquir Immune Defic Syndr, 2005; 39:537–544.
51.
AntelmanG, KaayaS, WeiR, et al.Depressive symptoms increase risk of HIV disease progression and mortality among women in Tanzania. J Acquir Immune Defici Syndr, 2007; 44:470–477.
52.
FialhoRM, PereiraM, MendoncaN, OuakininS. Depressive symptoms and neurocognitive performance among HIV-infected women. Women Health, 2013; 53:117–134.
53.
ArseniouS, ArvanitiA, SamakouriM. HIV infection and depression. Psychiatry Clin Neurosci, 2014; 68:96–109.
54.
ColeSR, HernanMA. Constructing inverse probability weights for marginal structural models. Am J Epidemiol, 2008; 168:656–664.
55.
KaharuzaFM, BunnellR, MossS, et al.Depression and CD4 cell count among persons with HIV infection in Uganda. AIDS Behav, 2006; 10:S105–S111.
56.
BackstromT, SandersD, LeaskR, DavidsonD, WarnerP, BancroftJ. Mood, sexuality, hormones, and the menstrual cycle. II. Hormone levels and their relationship to the premenstrual syndrome. Psychosom Med, 1983; 45:503–507.
57.
ArcherJS. NAMS/Solvay Resident Essay Award. Relationship between estrogen, serotonin, and depression. Menopause, 1999; 6:71–78.
58.
WeilandNG, OrchinikM. Specific subunit mRNAs of the GABAA receptor are regulated by progesterone in subfields of the hippocampus. Brain Res Mol Brain Res, 1995; 32:271–278.
59.
SmithSS, WaterhouseBD, ChapinJK, WoodwardDJ. Progesterone alters GABA and glutamate responsiveness: A possible mechanism for its anxiolytic action. Brain Res, 1987; 400:353–359.
60.
RobinsonSA, DowellM, PedullaD, McCauleyL. Do the emotional side-effects of hormonal contraceptives come from pharmacologic or psychological mechanisms?. Med Hypotheses, 2004; 63:268–273.
61.
SvendalG, BerkM, PascoJA, JackaFN, LundA, WilliamsLJ. The use of hormonal contraceptive agents and mood disorders in women. J Affect Disord, 2012; 140:92–96.
62.
HerzbergBN, JohnsonAL, BrownS. Depressive symptoms and oral contraceptives. Br Med J, 1970; 4:142–145.
63.
O'ConnellK, DavisAR, KernsJ. Oral contraceptives: Side effects and depression in adolescent girls. Contraception, 2007; 75:299–304.
64.
DukeJM, SibbrittDW, YoungAF. Is there an association between the use of oral contraception and depressive symptoms in young Australian women?. Contraception, 2007; 75:27–31.
65.
LawrieTA, HofmeyrGJ, De JagerM, BerkM, PaikerJ, ViljoenE. A double-blind randomised placebo controlled trial of postnatal norethisterone enanthate: The effect on postnatal depression and serum hormones. Br J Obstet Gynaecol, 1998; 105:1082–1090.
66.
WomackJA, ScherzerR, ColeSR, et al.Hormonal contraception and metabolic outcomes in women with or at risk for HIV infection. J Acquir Immune Defic Syndr, 2009; 52:581–587.
67.
MocroftA, PhillipsAN, GatellJ, et al.CD4 cell count and viral load-specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use. AIDS, 2013; 27:907–918.
68.
ReekieJ, GatellJM, YustI, et al.Fatal and nonfatal AIDS and non-AIDS events in HIV-1-positive individuals with high CD4 cell counts according to viral load strata. AIDS 28, 2011; 25:2259–2268.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
