Abstract: Investigating the association between hormonal contraception and HIV is challenging due to high discontinuation rates among users. This secondary analysis of 262 South African adolescent new users of hormonal contraception found continuation rates after 1 year for depot medroxyprogesterone acetate, norethisterone enanthate, or combined oral contraceptives of 40.4%, 64.4%, and 64.6%, respectively. Implications for studies evaluating the association between injectable hormonal contraceptive use and HIV are discussed.
*MatCH [Maternal, Adolescent, and Child Health], Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of the Witwatersrand, Durban, South Africa
†Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Correspondence to: Jennifer A. Smit, BPharm, MSc, PhD, MatCH [Maternal, Adolescent, and Child Health], Department of Obstetrics and Gynaecology, University of the Witwatersrand, 151 Juniper Road, Durban, 4091, South Africa (e-mail: firstname.lastname@example.org).
Supported by a grant from the World Health Organization and The William and Flora Hewlett Foundation.
The authors have no conflicts of interest to disclose.
Received July 03, 2012
Accepted October 28, 2012
Contraceptive use is high (69.7%) among young sexually active women aged 15–19 in South Africa,1 with 64.7% of those using a method using the injectable contraceptives norethisterone enanthate (NET-EN) and depot medroxyprogesterone acetate (DMPA). However, consistency of injectable use is poor, with high rates of discontinuation, breaks in use, and method switching,2–5 mainly due to side effects, especially menstrual disturbances.2,5 Similar patterns of injectable contraceptive use behavior are found in low-income, middle-income, and high-income countries worldwide.6–9
The potential for injectable hormonal contraception to increase the risk of HIV infection is an increasing concern with some studies showing an association with the injectable hormonal methods, primarily DMPA,10–12 and others showing no increased risk.13,14 In January 2012, a technical consultation regarding hormonal contraception and HIV was convened by the World Health Organization to assess current evidence15 and consider if the “Medical Eligibility Criteria for Contraceptive Use”16 should change. The consultation found that there was insufficient conclusive evidence to change current guidance. Further research was called for, and pressure is mounting to conduct high-quality studies to conclusively determine the relationship between hormonal contraception and HIV.13,15,17 Lack of good evidence on HIV risks with NET-EN use has in particular been cited as a research gap.12 High discontinuation rates and frequent method switching among injectable users pose challenges to successfully conducting trials.12 This secondary analysis examines patterns of contraceptive use over a 1-year period among adolescent participants of a bone mineral density (BMD) trial who were new users of hormonal contraception.
SUBJECTS AND METHODS
A cohort of adolescents aged 15–19 who self-selected use of DMPA, NET-EN, or combined oral contraceptives (COCs), or were nonusers of contraception, was recruited from a reproductive health clinic in Durban, South Africa, to participate in a BMD study. The study was conducted between 2000 and 2008. For inclusion into the study, women had to have no history of hormonal contraceptive use. There were 4 groups in total as follows: new users of DMPA (n = 115), NET-EN (n = 115), and COCs (n = 116), recruited on the day they commenced their hormonal method, and a group never having used a hormonal method (n = 144). On recruitment, a questionnaire was administered by a research nurse to elicit information on reproductive health history. A forearm BMD measurement was taken, and the results are published elsewhere.18
Study participants were followed-up at 6 monthly intervals for a total of 4–5 years, depending on time of recruitment. At each follow-up visit, details about contraceptive use for the preceding 6 months were collected verbally and confirmed from family planning cards. Any changes in method use including dates of method change were noted. The characteristics of women in the study were quantified as means±SD, medians, or percentages. Contraceptive use patterns across the first year of the study are summarized using frequencies and percentages.
Ethical approval was granted by the University of the Witwatersrand, Human Subjects Research Committee (protocol number M981001), and by the Scientific and Ethical Review Group of the World Health Organization.
In total, 490 women aged 15–19 years were recruited. The 4 groups had similar sociodemographic characteristics. Their median age was 18 years, and almost all were African except the COC group with 22% of Indian women.
Follow-up at 1 year was 82% (n = 401). Of these women, 31 presented with criteria that made them ineligible to continue in the study, leaving 370 eligible women with follow-up rates of DMPA 77% (n = 89), NET-EN 79% (n = 91), COC 71% (n = 82), and nonusers 75% (n = 108). There were no differences in age or other baseline characteristics between the contraceptive user groups and women who discontinued.
Table 1 shows contraceptive status at 1 year of the hormonal contraceptive users compared with baseline method use. Of those who continued participation in the study for at least 1 year, no more than two-thirds of NET-EN users (64.4%) and COC users (64.6%) continued on the same method without a break. For DMPA users, this was even lower at 40.4%. Almost a quarter (22.5%) of DMPA users changed to another hormonal method, and this was mainly NET-EN (85%, n = 17), whereas some stopped use altogether with no switch to another hormonal method (29.2%). A small number of women across all 3 methods had a short break and returned to the same method within the year. In the nonuser group, 12.2% started using a hormonal method within the first year. Over the following years of follow-up, high rates of switching, breaks, and discontinuation continued but were highest in the DMPA group where by 2 years, 74% had changed method or stopped use. Anecdotal reports of reasons for method change were commonly change in relationship status or method-related side effects.
Our data show that patterns of contraceptive use among trial participants are complex, with high discontinuation and method switching rates, especially among DMPA users. Another South African HIV prevention trial also reported high levels of method switching.13 In this Carraguard phase 3 efficacy trial over one-third (35.6%) of South African women ever switched their method during participation in the trial, with switching occurring among 31% of DMPA and 40% of NET-EN users. Switching between hormonal methods without a “washout” period may be problematic in analysis if these participants are not censored. Women may also have “short breaks” of a few weeks or a few months before returning to the same method but may report they are still using the method. This may particularly affect retrospective data collection leading to distortion in the interpretation of findings from studies on hormonal contraceptive use. In addition, users of injectable hormonal methods should not be analyzed together,19 as their modes of action may be different as is the case with DMPA and NET-EN.20
Cognizance must be taken of adherence issues in contraceptive use when planning trials (or reanalyzing trial data) to investigate the association between hormonal contraception and HIV in high HIV prevalence countries. Loss to follow-up and poor adherence are particularly important factors to consider when calculating a sample size that will adequately address the questions posed. The conflicting data on the association between use of hormonal methods and HIV infection is no doubt partly due to analyzing data with complex patterns of contraceptive use. High quality contraceptive services and counseling to improve adherence are routinely provided in HIV prevention trials and may be implemented in future studies investigating hormonal contraception and HIV. Although this may decrease discontinuation rates, users may become more informed about other contraceptive methods, which may lead to method switching.
1. National Department of Health. Medical research Council, OrcMacro. South Africa Demographic and Health Survey 2003. Pretoria, South Africa: National Department of Health; 2007.
2. Beksinska ME, Rees HV, Smit J. Temporary discontinuation: a compliance issue in injectable users. Contraception2001;64:309–313.
3. National Department of Health. Medical Research Council and Measure DHS+. South Africa Demographic and Health Survey 1998, Full Report. Pretoria, South Africa: National Department of Health; 2002.
4. Beksinska ME, Rees H, Nkonyane T, et al.. Compliance and use behaviour, an issue in injectable as well as oral contraceptive use? A study of injectable and oral contraceptive users in Johannesburg. Br J Fam Plann. 1998;24:15–18.
5. Beksinska ME, Kleinschmidt I, Smit JA, et al.. Bone mineral density in young women aged 19-24 after 4-5 years of exclusive and mixed use of hormonal contraception. Contraception. 2009;80:128–132.
6. Ali MM, Cleland J. Contraceptive switching after method-related discontinuation: levels and differentials. Stud Fam Plann. 2010;41:129–133.
7. Barden-O’Fallon J, Speizer I. What differentiates method stoppers from switchers? Contraceptive discontinuation and switching among Honduran women. Int Perspect Sex Reprod Health. 2011;37:16–23.
8. Peipert JF, Zhao Q, Allsworth JE, et al.. Continuation and satisfaction of reversible contraception. Obstet Gynecol. 2011;117:1105–1113.
9. Raine TR, Foster-Rosales A, Upadhyay UD, et al.. One-year contraceptive continuation and pregnancy in adolescent girls and women initiating hormonal contraceptives. Obstet Gynecol. 2011;117:363–371.
10. Morrison CS, Chen P, Kwok C, et al.. Hormonal contraception and HIV acquisition: reanalysis using marginal structural modelling. AIDS. 2010;24:1778–1781.
11. Baeten JM, Benki S, Chohan V, et al.. Hormonal contraceptive use, herpes simplex virus infection, and the risk of HIV-1 acquisition among Kenyan women. AIDS. 2007;21:1771–1777.
12. Heffron R, Donnell D, Rees H, et al.. Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study. Lancet Infect Dis. 2012;12:19–26.
13. Morrison CS, Skoler-Karpoff S, Kwok C, et al.. Hormonal contraception and the risk of HIV acquisition among women in South Africa. AIDS. 2012;26:497–504.
14. Kleinschmidt I, Rees H, Delany S, et al.. Injectable progestin contraceptive use and risk of HIV infection in a South African family planning cohort. Contraception. 2007;75:461–467.
15. World Health Organization. Department of Reproductive Health and Research. Hormonal Contraception and HIV, Technical Statement. Geneva, Switzerland: World Health Organization; 2012.
16. World Health Organization. Department of Reproductive Health and Research. The Medical Eligibility Criteria for Contraceptive Use, Fourth Edition. Geneva, Switzerland: World Health Organization; 2009.
17. World Health Organization. Department of Reproductive Health and Research. Programmatic and Research Considerations for Hormonal Contraception for Women at Risk of HIV and Women Living with HIV, Policy Implications. Geneva, Switzerland: World Health Organization; 2012.
18. Beksinska ME, Kleinschmidt I, Smit JA, et al.. Bone mineral density in a cohort of adolescents during use of norethisterone enanthate, depot-medroxyprogesterone acetate or combined oral contraceptives and after discontinuation of norethisterone enanthate. Contraception. 2009;79:345–349.
19. Beksinska ME, Smit J, Kleinschmidt I. HIV-1 transmission risks from norethisterone enanthate and depot-medroxyprogesterone acetate should be evaluated separately. Lancet Infect Dis. 2012;12:509.
20. Hapgood JP, Koubovec D, Louw A, et al.. Not all progestins are the same: implications for usage. Trends Pharmacol Sci. 2004;11:554–557.