Brind, J., Condly, S. J., Mosher, S. W., Morse, A. R., & Kimball, J. (2015). Risk of HIV Infection in Depot-Medroxyprogesterone Acetate (DMPA) Users: A Systematic Review and Meta-analysis. Issues in law & medicine, 30(2), 129-139.
Brind J, Condly SJ, Mosher SW, Morse AR, Kimball J. Risk of HIV Infection in Depot-Medroxyprogesterone Acetate (DMPA) Users: A Systematic Review and Meta-analysis. Issues Law Med. 2015;30(2):129-139.
Brind, J., et al. "Risk of HIV Infection in Depot-Medroxyprogesterone Acetate (DMPA) Users: A Systematic Review and Meta-analysis." Issues in law & medicine, vol. 30, no. 2, 2015, pp. 129-139.
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As the HIV/AIDS epidemic continues to spread in Africa and Asia, use of the injectable contraceptive steroid DMPA is widespread and has been increasing. Since studies dating back to 1992 have suggested that DMPA may increase the transmission of HIV to women, we endeavored to determine if the extant epidemiological and biological evidence is sufficient to conclude that DMPA use constitutes a definite hazard to women's health.
Methods
We searched Medline using the search terms: contraceptives or contraception AND HIV and searched bibliographies of articles thus identified. We included in the meta-analysis all studies examining the association between use of DMPA (or injectable contraceptives comprising mostly DMPA) and the presence (cross-sectional studies, n = 8) or acquisition (longitudinal studies, n = 16) of HIV+ status in women, using a random effects models to estimate odds ratios (ORs; cross-sectional studies) and hazard ratios (HRs; longitudinal studies). Studies were excluded if the comparison group included women using any form of steroidal contraception.
Results
Statistically significant positive associations between DMPA use and HIV positivity were observed both in cross-sectional (OR = 1.41, 95% CI 1.15 - 1.73) and longitudinal studies (HR = 1.49, 95% CI 1.28 - 1.73). The biological plausibility of increased vulnerability to HIV infection due to progestational action (via thinning of the vaginal epithelial barrier and immunosuppression) as well as glucocorticoid agonistic immunosuppression, are discussed.
Conclusion
The epidemiological and biological evidence now make a compelling case that DMPA adds significantly to the risk of male-to-female HIV transmission.
Williams WV et al., 2021·Linacre Q·Free full text on PubMed Central
To investigate the sociological, environmental, and economic impact of hormonally active contraceptives, a series of comprehensive literature surveys were employed. Sociological effects are discussed including abortion, exploitation of women, a weakening of marriage, and an increase in divorce with deleterious effects on children such as child poverty, poorer health, lower educational achievement, suicide risks, drug and alcohol abuse, criminality, and incarceration, among others. The environmental impact is discussed briefly and includes the feminization and trans-gendering of male fish downstream from the effluent of city wastewater treatment plants with declining fish populations. The potential economic impact of most of these side effects is estimated based on epidemiologic data and published estimates of costs of caring for the diseases which are linked to the use of hormonally active contraceptives. Hormonally active contraceptives appear to have a deleterious impact on multiple aspects of women's health as well as negative economic and environmental impacts. These risks can be avoided through the use of nonhormonal methods and need to be more clearly conveyed to the public.
Hormonal contraceptives have wide-ranging effects. The potential economic impact of the medical side effects is estimated. Sociological effects are discussed including abortion, exploitation of women, a weakening of marriage and an increase in divorce with negative effects on children such as child poverty, poorer health, lower educational achievement, suicide risks, drug and alcohol abuse, criminality and incarceration among others. The environmental impact includes hormonal effects on fish with declining fish populations. Women seeking birth control have a right to know about how to avoid these risks by using effective hormone-free methods like Fertility Awareness Methods.
Williams WV et al., 2021·Linacre Q·Free full text on PubMed Central
Hormonal contraceptives have been on the market for over fifty years and, while their formulations have changed, the basic mechanism of action has remained the same. During this time, numerous studies have been performed documenting side effects, some of which appear over time, some within weeks or months, but all can have a serious impact on health and quality of life. An effort was made to perform a series of comprehensive literature surveys to better understand immediate and long-term side effects of these agents. The results of this literature review uncovered a number of potential side effects, some of which are acknowledged and many of which are not noted in the prescribing information for these agents. Among the unacknowledged side effects are: an increased risk of HIV transmission for depot medroxyprogesterone acetate (DMPA), and for combination contraceptives breast cancer, cervical cancer, Crohn's disease, ulcerative colitis, systemic lupus erythematosus, depression, mood disorders and suicides (especially among women twenty-five years of age and younger, in the first six months of use), multiple sclerosis, interstitial cystitis, female sexual dysfunction, osteoporotic bone fractures (especially for progesterone-only contraceptives), and fatty weight gain. Misleading prescribing information regarding cardiovascular and thrombotic risks are also noted. Women seeking birth control have a right to be informed and educated about risk avoidance through the use of effective nonhormonal methods like fertility awareness methods. In one case-that of DMPA-the increased risk of HIV acquisition has been conclusively demonstrated to be both real and unique to this drug. Considering the availability of numerous alternatives, there is no justification for the continued marketing of DMPA to the public.
We reviewed the effect of hormonal contraceptives on women's health. A number of potential side effects were noted including increased risks of breast cancer, cervical cancer, inflammatory bowel disease, lupus, multiple sclerosis, cystitis, bone fractures, depression, mood disorders and suicides, fatty weight gain, and female sexual dysfunction. With the long-acting injectable contraceptives there is an increased risk of getting HIV. Misleading prescribing information regarding the risks of heart attacks, strokes and blood clotting problems were also noted. Women seeking birth control have a right to know about how to avoid these risks by using effective hormone-free Fertility Awareness Methods.
Some women who take mifepristone, a progesterone receptor antagonist, in order to terminate their pregnancies, change their minds and desire to stop the medical abortion process. There are only two articles in the medical literature documenting the reversal of the effects of mifepristone.
We present and analyze a series of women who attempted to reverse the effects of mifepristone by taking supplemental progesterone to determine if the reversal of the effects mifepristone with progesterone is possible and safe. Additionally, we compare different progesterone regimens to determine relative efficacies.
This is an observational case series of 754 patients who decided to attempt to reverse the medical abortion process after taking mifepristone but before taking the second drug in the protocol, misoprostol. We followed the patients, who were given progesterone in an effort to reverse the effects of mifepristone, and conducted statistical analyses to determine the efficacies of different protocols compared to a control mifepristone embryo survival rate, derived from the literature.
Intramuscular progesterone and high dose oral progesterone were the most effective with reversal rates of 64% (P < 0.001) and 68% (P < 0.001), respectively. There was no apparent increased risk of birth defects. The reversal of the effects of mifepristone using progesterone is safe and effective.
Morrison CS et al., 2015·PLoS Med·Free full text on PubMed Central
Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC. Findings: Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15-49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37,124 women (43,613 woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84-1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study heterogeneity was mild (I(2) < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use 0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (p(interaction) = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship. This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.
To investigate whether the incidence of HIV infection is higher among sexually active women using depot medroxyprogesterone acetate (DMPA) or noresthisterone enanthate (NET-EN) injections for contraception than among women using nonhormonal or no contraception. Five hundred and fifty-one initially HIV-negative women were followed up for a total of 491 person-years. Participants were interviewed, counselled, examined, tested for HIV and other STIs, and treated, at three monthly intervals for 1 year. There was no significant association between progestin contraceptive use and HIV infection (rate ratio 1.1, 95% CI 0.5 to 2.8; log-rank test, p=.73). In proportional hazards regression, the only significant hazard ratios for HIV acquisition were prevalent Neisseria gonorrhoea (5.2; 95% CI 1.1 to 23.7, p=.035) and Trichomonas vaginalis (4.8; 95% CI 1.0 to 22.8, p=.049); bacterial vaginosis was marginally significant (2.8; 95% CI 1.0 to 8.3, p=.057). The adjusted hazard ratios for NET-EN and DMPA were 1.76 (95% CI 0.64 to 4.84) and 0.46 (95% CI 0.06 to 3.79), respectively, relative to nonuse. Five hundred and twelve of 551 women had one or more confirmed STIs during the study. There is no evidence of an association between HIV infection and injectable contraceptives. Due to the limited power of this study and because similar studies have not included young women using NET-EN, we recommend that further research be carried out to focus on the use of NET-EN and HIV acquisition in high risk groups.
Comparative Studies · Contraception Versus Fertility Awareness
Hapgood JP, 2020·AIDS research and human retroviruses·Free full text on PubMed Central
Intramuscular depo-medroxyprogesterone acetate (DMPA-IM) is the most widely used hormonal contraceptive in sub-Saharan Africa. Previous meta-analyses of observational studies found a significant 40%-50% increased risk associated with DMPA-IM use, relative to no contraception or infrequent condom use. This raised substantial concerns, although these studies had important limitations. Consequently, the open-label randomized Evidence for Contraceptive Options and HIV Outcomes trial was conducted, designed primarily to detect a 50% or greater difference in HIV risk between DMPA-IM, the levonorgestrel (LNG) implant, and the copper-intrauterine device. The ECHO study, published in July 2019, concluded that there is no substantial difference in HIV risk among the methods evaluated, and that all three methods are safe and highly effective. In response, the WHO relaxed the Medical Eligibility Criteria for DMPA-IM use among women at high HIV risk in August 2019. However, two of the three comparisons in the ECHO trial could rule out neither a 50% increase nor no change in HIV risk for one contraceptive compared with another. The study had limitations and the results contained considerable uncertainty. They also did not inform on associated HIV risk for any one of the individual methods due to the absence of a control group such as no contraception or only infrequent condom use. The HIV risks associated with LNG implant and copper-IUD relative to no contraception or infrequent condom use are unknown and these cannot be seen as controls, nor did the authors claim them to be. The results will be discussed in the context of their limitations, what they add to the body of work to date on contraception and HIV acquisition, and the implications of the findings and reports thereof for future research and contraceptive choice.
Ralph LJ et al., 2015·Lancet Infect Dis·Free full text on PubMed Central
The evidence from epidemiological research into whether use of hormonal contraception increases women's risk of HIV acquisition is inconsistent. We did a robust meta-analysis of existing data to provide summary estimates by hormonal contraceptive method which can be used to inform contraceptive guidelines, models, and future studies. We updated a recent systematic review to identify and describe studies that met inclusion criteria. To ensure inclusion of more recent research, we searched PubMed for articles published after December, 2011, using the terms "hormonal contraception", "HIV/acquisition", "injectables", "progestin", and "oral contraceptive pills". We assessed statistical heterogeneity for these studies, and, when appropriate, combined point estimates by hormonal contraception formulation using random-effects models. We assessed publication bias and investigated heterogeneity through subgroup and stratified analyses according to study population and design features. Findings: We identified 26 studies, 12 of which met inclusion criteria. There was evidence of an increase in HIV risk in the ten studies of depot medroxyprogesterone acetate (pooled hazard ratio [HR] 1·40, 95% CI 1·16-1·69). This risk was lower in the eight studies done in women in the general population (pooled HR 1·31, 95% CI 1·10-1·57). There was substantial between-study heterogeneity in secondary analyses of trials (n=7, I(2) 51·1%, 95% CI 0-79·3). Although individual study estimates suggested an increased risk, substantial heterogeneity between two studies done in women at high risk of HIV infection (I(2) 54%, 0-88·7) precluded pooling estimates. There was no evidence of an increased HIV risk in ten studies of oral contraceptive pills (pooled HR 1·00, 0·86-1·16) or five studies of norethisterone enanthate (pooled HR 1·10, 0·88-1·37). Interpretation: Our findings show a moderate increased risk of HIV acquisition for all women using depot medroxyprogesterone acetate, with a smaller increase in risk for women in the general population. Whether the risks of HIV observed in our study would merit complete withdrawal of depot medroxyprogesterone acetate needs to be balanced against the known benefits of a highly effective contraceptive. None.
Contraception › Adverse Effects › Bone Density Effects · General Gynecology › Infections › Vaginal and Cervical Infections
Joel Brind
J Brind
PMID 26710371 26710371 Brind et al. 2015, Brind 2015
Cite this article
Brind, J., Condly, S. J., Mosher, S. W., Morse, A. R., & Kimball, J. (2015). Risk of HIV Infection in Depot-Medroxyprogesterone Acetate (DMPA) Users: A Systematic Review and Meta-analysis. Issues in law & medicine, 30(2), 129-139.
Brind J, Condly SJ, Mosher SW, Morse AR, Kimball J. Risk of HIV Infection in Depot-Medroxyprogesterone Acetate (DMPA) Users: A Systematic Review and Meta-analysis. Issues Law Med. 2015;30(2):129-139.
Brind, J., et al. "Risk of HIV Infection in Depot-Medroxyprogesterone Acetate (DMPA) Users: A Systematic Review and Meta-analysis." Issues in law & medicine, vol. 30, no. 2, 2015, pp. 129-139.
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