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Contraception Dec 2016Women with medical conditions associated with increased risk for thrombosis generally should not use estrogen-containing contraceptives; however, less is known about... (Review)
Review
BACKGROUND
Women with medical conditions associated with increased risk for thrombosis generally should not use estrogen-containing contraceptives; however, less is known about progestin-only contraceptives (POCs) and thrombosis risk.
OBJECTIVES
The objective was to identify evidence regarding the risk of venous thromboembolism (VTE) or arterial thromboembolism [stroke or acute myocardial infarction (AMI)] among women using POCs.
METHODS
We searched the PubMed database for all articles published from database inception through January 2016 for studies examining thrombosis among women using POCs. We included studies which examined women with medical conditions associated with thrombosis risk, as well as studies of women in the general population (either without these conditions or who were not specified to have these conditions). Hormonal contraceptives of interest included progestin-only pills (POPs), injectables, implants and levonorgestrel-releasing intrauterine devices (LNG-IUDs). Outcomes of interest included VTE, stroke and AMI.
RESULTS
There were 26 articles of good to poor quality that met inclusion criteria; 9 studies examined women with medical conditions and 20 examined women in the general population. Two studies found that, among smokers and women with certain thrombogenic mutations, use of depot medroxyprogesterone acetate (DMPA) had elevated odds of VTE compared with nonsmokers or those without mutations, although confidence intervals were wide and overlapped with odds among nonusers. One study found that, among women with previous VTE, use of POCs (including DMPA) was associated with a nonsignificant increased odds of recurrent VTE (all of which were among DMPA users); two other studies that examined POCs other than DMPA did not observe an association with recurrent VTE. Two studies found that use of DMPA among healthy women was also associated with increased odds of VTE. Two studies found that use of POCs for therapeutic indications was associated with increased odds of VTE. Studies did not find increased odds of VTE with POPs for contraceptive purposes, implants or LNG-IUDs nor were there increased odds of stroke or AMI with any POCs.
CONCLUSION
The majority of evidence identified by this systematic review did not suggest an increase in odds for venous or arterial events with use of most POCs. Limited evidence suggested increased odds of VTE with use of injectables (three studies) and use of POCs for therapeutic indications (two studies, one with POCs unspecified and the other with POPs). Any increase in risk likely translates to a small increase in absolute numbers of thrombotic events at the population level.
Topics: Contraception; Female; Humans; Myocardial Infarction; Progestins; Risk Assessment; Stroke; Venous Thromboembolism; Weight Gain
PubMed: 27153743
DOI: 10.1016/j.contraception.2016.04.014 -
The Cochrane Database of Systematic... Aug 2016Progestin-only contraceptives (POCs) are appropriate for many women who cannot or should not take estrogen. POCs include injectables, intrauterine contraception,... (Review)
Review
BACKGROUND
Progestin-only contraceptives (POCs) are appropriate for many women who cannot or should not take estrogen. POCs include injectables, intrauterine contraception, implants, and oral contraceptives. Many POCs are long-acting, cost-effective methods of preventing pregnancy. However, concern about weight gain can deter the initiation of contraceptives and cause early discontinuation among users.
OBJECTIVES
The primary objective was to evaluate the association between progestin-only contraceptive use and changes in body weight.
SEARCH METHODS
Until 4 August 2016, we searched MEDLINE, CENTRAL, POPLINE, LILACS, ClinicalTrials.gov, and ICTRP. For the initial review, we contacted investigators to identify other trials.
SELECTION CRITERIA
We considered comparative studies that examined a POC versus another contraceptive method or no contraceptive. The primary outcome was mean change in body weight or mean change in body composition. We also considered the dichotomous outcome of loss or gain of a specified amount of weight.
DATA COLLECTION AND ANALYSIS
Two authors extracted the data. Non-randomized studies (NRS) need to control for confounding factors. We used adjusted measures for the primary effects in NRS or the results of matched analysis from paired samples. If the report did not provide adjusted measures for the primary analysis, we used unadjusted outcomes. For RCTs and NRS without adjusted measures, we computed the mean difference (MD) with 95% confidence interval (CI) for continuous variables. For dichotomous outcomes, we calculated the Mantel-Haenszel odds ratio (OR) with 95% CI.
MAIN RESULTS
We found 22 eligible studies that included a total of 11,450 women. With 6 NRS added to this update, the review includes 17 NRS and 5 RCTs. By contraceptive method, the review has 16 studies of depot medroxyprogesterone acetate (DMPA), 4 of levonorgestrel-releasing intrauterine contraception (LNG-IUC), 5 for implants, and 2 for progestin-only pills.Comparison groups did not differ significantly for weight change or other body composition measure in 15 studies. Five studies with moderate or low quality evidence showed differences between study arms. Two studies of a six-rod implant also indicated some differences, but the evidence was low quality.Three studies showed differences for DMPA users compared with women not using a hormonal method. In a retrospective study, weight gain (kg) was greater for DMPA versus copper (Cu) IUC in years one (MD 2.28, 95% CI 1.79 to 2.77), two (MD 2.71, 95% CI 2.12 to 3.30), and three (MD 3.17, 95% CI 2.51 to 3.83). A prospective study showed adolescents using DMPA had a greater increase in body fat (%) compared with a group not using a hormonal method (MD 11.00, 95% CI 2.64 to 19.36). The DMPA group also had a greater decrease in lean body mass (%) (MD -4.00, 95% CI -6.93 to -1.07). A more recent retrospective study reported greater mean increases with use of DMPA versus Cu IUC for weight (kg) at years 1 (1.3 vs 0.2), 4 (3.5 vs 1.9), and 10 (6.6 vs 4.9).Two studies reported a greater mean increase in body fat mass (%) for POC users versus women not using a hormonal method. The method was LNG-IUC in two studies (reported means 2.5 versus -1.3; P = 0.029); (MD 1.60, 95% CI 0.45 to 2.75). One also studied a desogestrel-containing pill (MD 3.30, 95% CI 2.08 to 4.52). Both studies showed a greater decrease in lean body mass among POC users.
AUTHORS' CONCLUSIONS
We considered the overall quality of evidence to be low; more than half of the studies had low quality evidence. The main reasons for downgrading were lack of randomizations (NRS) and high loss to follow-up or early discontinuation.These 22 studies showed limited evidence of change in weight or body composition with use of POCs. Mean weight gain at 6 or 12 months was less than 2 kg (4.4 lb) for most studies. Those with multiyear data showed mean weight change was approximately twice as much at two to four years than at one year, but generally the study groups did not differ significantly. Appropriate counseling about typical weight gain may help reduce discontinuation of contraceptives due to perceptions of weight gain.
Topics: Adolescent; Adult; Body Composition; Body Weight; Contraceptives, Oral, Hormonal; Drug Implants; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Medroxyprogesterone Acetate; Progestins; Prospective Studies; Retrospective Studies; Weight Gain
PubMed: 27567593
DOI: 10.1002/14651858.CD008815.pub4 -
Archives of Gynecology and Obstetrics Apr 2024Short-acting progestin-only injectables containing depot medroxyprogesterone acetate (DMPA) are a safe method of contraception. Although DMPA has been available for... (Review)
Review
PURPOSE
Short-acting progestin-only injectables containing depot medroxyprogesterone acetate (DMPA) are a safe method of contraception. Although DMPA has been available for several decades, there is little data on its influence on the risk of breast cancer. Hence, the aim of this paper was to provide an overview of the existing studies and create clarity regarding a possible association with breast cancer.
METHODS
Literature searches were executed in MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and ICTRP. Search terms were related to DMPA and breast cancer. After elimination of duplicates, 3'850 studies were identified and assessed according to inclusion and exclusion criteria. Finally, ten studies were selected and included in this review.
RESULTS
All the selected papers were case-control-studies, except for one pooled analysis and one study comparing observed and expected number of cancer cases. Most of the included studies found no overall elevated breast cancer incidence in DMPA users, only one study found a slightly increased risk and two studies concluded with a significant increase for the overall breast cancer risk.
CONCLUSION
There is little evidence that DMPA may increase the overall risk for breast cancer. However, the incidence of breast cancer is possibly increased in current and more recent users, especially in women younger than 35 years. Long-term use did not result in any risk increase. Nevertheless, further studies will be necessary to confirm these findings and weigh up the individual risks and benefits of this contraceptive method.
Topics: Female; Humans; Medroxyprogesterone Acetate; Delayed-Action Preparations; Breast Neoplasms; Contraceptive Agents, Female; Progestins
PubMed: 37966517
DOI: 10.1007/s00404-023-07265-5 -
BMC Women's Health Oct 2021Subcutaneous depot medroxyprogesterone acetate is an easy-to-use injectable contraceptive. A trained person can administer it, including women through self-injection.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Subcutaneous depot medroxyprogesterone acetate is an easy-to-use injectable contraceptive. A trained person can administer it, including women through self-injection. The objective of this systematic review and meta-analysis was to assess the effectiveness and safety of self-injection versus provider-administered subcutaneous depot medroxyprogesterone acetate for improving continuation of contraceptive use.
METHODS
We searched for randomized controlled trials on November 1, 2020 in Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, Embase, Web of Science, Scopus, Open Grey, clinical trials registries, and reference lists of relevant studies. We did not impose any search restrictions. We included randomized trials comparing self- versus provider-administered subcutaneous depot medroxyprogesterone acetate. Two authors independently screened trials, extracted data, and assessed the risk of bias in the included studies. We used risk ratio and 95% confidence intervals for dichotomous outcomes.
RESULTS
We identified 3 randomized trials (9 reports; 1264 participants). The risk of bias in the included studies was low except for performance bias and detection bias of participant-reported outcomes in unmasked trials. Self-administration, compared to provider-administration, increased continuation of contraceptive use (risk ratio 1.35; 95% confidence intervals 1.10-1.66); moderate-certainty evidence). Self-injection appears to be making more of an impact on continuation for younger women compared to women 25 years and older and on women living in low and middle income compared to high income countries. There was no subgroup difference by the type of care provider (community health worker vs. clinic-based provider).
CONCLUSIONS
Self-injection of subcutaneous depot medroxyprogesterone acetate probably improves continuation of contraceptive use. The effects on other outcomes remain uncertain because of the very low certainty of evidence.
Topics: Community Health Workers; Contraceptive Agents, Female; Female; Humans; Injections; Medroxyprogesterone Acetate; Self Administration
PubMed: 34627229
DOI: 10.1186/s12905-021-01495-y -
Brazilian Journal of Medical and... 2018Because of weight gain, women often discontinue hormonal contraception, especially depot medroxyprogesterone acetate (DMPA). Our objective was to conduct a systematic... (Review)
Review
Because of weight gain, women often discontinue hormonal contraception, especially depot medroxyprogesterone acetate (DMPA). Our objective was to conduct a systematic review of studies describing dietary intake or eating behavior in DMPA users to understand whether the use of DMPA is associated with changes in dietary habits and behaviors leading to weight gain. We searched the PubMed, POPLINE, CENTRAL Cochrane, Web of Science, and EMBASE databases for reports published in English between 1980 and 2017 examining dietary intake or eating behavior in healthy women in reproductive age and adolescents using DMPA (150 mg/mL). Of the 749 publications screened, we excluded 742 due to duplicates (96), not addressing the key research question (638), not reporting dietary intake data (4), and not evaluating the relationship of body weight and dietary or eating behaviors (4). We identified seven relevant studies, including one randomized placebo-controlled trial, one non-randomized paired clinical trial, and five cohort studies. The randomized trial found no association and the other reports were inconsistent. Findings varied from no change in dietary intake or eating behavior with DMPA use to increased appetite in the first six months of DMPA use. Few studies report dietary intake and eating behavior in DMPA users and the available data are insufficient to conclude whether DMPA use is associated with changes in dietary habits or behavior leading to weight gain.
Topics: Body Mass Index; Clinical Trials as Topic; Contraceptive Agents, Female; Energy Intake; Feeding Behavior; Female; Humans; Medroxyprogesterone Acetate; Weight Gain
PubMed: 29694506
DOI: 10.1590/1414-431x20187575 -
AIDS (London, England) Apr 2017To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals. (Review)
Review
OBJECTIVE
To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals.
DESIGN
Systematic review of the published literature.
METHODS
We searched PubMed, POPLINE, and EMBASE for peer-reviewed publications of studies (in any language) from inception to 21 September 2015. We included studies of women using hormonal contraceptives and antiretrovirals concurrently. Outcomes of interest were effectiveness of either therapy, toxicity, or pharmacokinetics. We used standard abstraction forms to summarize and assess strengths and weaknesses.
RESULTS
Fifty reports from 46 studies were included. Most antiretrovirals whether used for therapy or prevention, have limited interactions with hormonal contraceptive methods, with the exception of efavirenz. Although depot medroxyprogesterone acetate is not affected, limited data on implants and combined oral contraceptive pills suggest that efavirenz-containing combination antiretroviral therapy may compromise contraceptive effectiveness of these methods. However, implants remain very effective despite such drug interactions. Antiretroviral plasma concentrations and effectiveness are generally not affected by hormonal contraceptives.
CONCLUSION
Women taking antiretrovirals, for treatment or prevention, should not be denied access to the full range of hormonal contraceptive options, but should be counseled on the expected rates of unplanned pregnancy associated with all contraceptive methods, in order to make their own informed choices.
Topics: Anti-Retroviral Agents; Contraceptives, Oral, Hormonal; Drug Interactions; Female; Humans
PubMed: 28060009
DOI: 10.1097/QAD.0000000000001392 -
Reproductive Health Aug 2013Use of depot medroxyprogesterone acetate (DMPA), often known by the brand name Depo-Provera, has increased globally, particularly in multiple low- and middle-income... (Review)
Review
BACKGROUND
Use of depot medroxyprogesterone acetate (DMPA), often known by the brand name Depo-Provera, has increased globally, particularly in multiple low- and middle-income countries (LMICs). As a reproductive health technology that has scaled up in diverse contexts, DMPA is an exemplar product innovation with which to illustrate the utility of the AIDED model for scaling up family health innovations.
METHODS
We conducted a systematic review of the enabling factors and barriers to scaling up DMPA use in LMICs. We searched 11 electronic databases for academic literature published through January 2013 (n = 284 articles), and grey literature from major health organizations. We applied exclusion criteria to identify relevant articles from peer-reviewed (n = 10) and grey literature (n = 9), extracting data on scale up of DMPA in 13 countries. We then mapped the resulting factors to the five AIDED model components: ASSESS, INNOVATE, DEVELOP, ENGAGE, and DEVOLVE.
RESULTS
The final sample of sources included studies representing variation in geographies and methodologies. We identified 15 enabling factors and 10 barriers to dissemination, diffusion, scale up, and/or sustainability of DMPA use. The greatest number of factors were mapped to the ASSESS, DEVELOP, and ENGAGE components.
CONCLUSIONS
Findings offer early empirical support for the AIDED model, and provide insights into scale up of DMPA that may be relevant for other family planning product innovations.
Topics: Contraceptive Agents, Female; Delayed-Action Preparations; Female; Health Services Accessibility; Humans; Medroxyprogesterone Acetate; Models, Theoretical; Reproductive Health Services
PubMed: 23915274
DOI: 10.1186/1742-4755-10-39 -
Open Access Journal of Contraception 2018Evidence on the association between contraceptive use and risk of sexually transmitted infections (STIs) and bacterial vaginosis (BV) is lacking, with few prospective... (Review)
Review
PURPOSE
Evidence on the association between contraceptive use and risk of sexually transmitted infections (STIs) and bacterial vaginosis (BV) is lacking, with few prospective studies. We systematically reviewed the last 10 years' evidence on the association between contraception and STI/BV, building on the most recent systematic reviews published in 2006 and 2009.
METHODS
We searched the MEDLINE and POPLINE databases for peer-reviewed articles p ublished between January 1, 2008 and January 31, 2018 reporting prospective studies that assessed the association between contraceptive use and incident STI and/or incident or recurrent BV.
RESULTS
We identified 33 articles that evaluated combined oral contraceptives (COC), depot medroxyprogesterone acetate (DMPA), the copper intrauterine device (Cu-IUD), the levonorgestrel intrauterine system (LNG-IUS) and other methods. The strength of the evidence for many specific contraceptive method/STI associations is limited by few prospective studies with comparably defined exposures and outcomes. Available data suggest no association of COCs and , , HSV-2 or syphilis, and mixed evidence on the association with HPV, , and BV. For DMPA, none of the studies identified found an association with or syphilis, and data on HPV and BV were mixed. Two large studies showed a highly clinically significant increased risk of HSV-2 infection with DMPA use. Data on the effect of Cu-IUD and the LNG-IUS on the acquisition of , and s are sparse, and data on HPV and BV are mixed.
CONCLUSION
Few data are available from prospective studies, including randomized trials, to draw strong conclusions about the relationships between contraceptive methods and specific STIs. The overall evidence on the association between contraceptive use and STI/BV risk is limited by the lack of any randomized trials, few published prospective studies designed to analyze these associations, wide variability in exposure definitions and comparator groups, potential for confounding due to inaccurate sexual behavior data, differential confounder adjustment and differences in study populations and sizes. Despite these limitations, new evidence is supportive of a significantly increased risk of HSV-2 infection among DMPA users which warrants additional research to better understand this association.
PubMed: 30519127
DOI: 10.2147/OAJC.S135439 -
Contraception Sep 2016Depot medroxyprogesterone acetate (DMPA), a progestogen-only contraceptive injectable, has traditionally been formulated as a crystalline suspension delivered... (Review)
Review
CONTEXT
Depot medroxyprogesterone acetate (DMPA), a progestogen-only contraceptive injectable, has traditionally been formulated as a crystalline suspension delivered intramuscularly (IM) at a dose of 150mg/1.0mL. A new, lower dose formulation of DMPA (104mg/0.65mL) has been developed for subcutaneous administration (SC). Given its increasing global availability and public health relevance, DMPA-SC was prioritized for inclusion as a new method referenced in the World Health Organization (WHO) Medical Eligibility Criteria for Contraceptive Use (MEC), 5th Edition.
OBJECTIVE
This systematic review evaluated the published peer-reviewed literature regarding the safety of DMPA-SC among women with various characteristics or medical conditions. Results of this review informed the decision-making of a WHO Guideline Development Group in order to include recommendations on contraceptive eligibility within the revised MEC.
METHODS
We searched PubMed and Cochrane Library databases to identify all relevant evidence published in peer-reviewed journals regarding the safety of DMPA-SC when used by women of reproductive age, particularly those with select characteristics or conditions specified in the MEC, from inception through June 2015. The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force.
RESULTS
Fourteen studies met criteria for inclusion. Ten reported results relevant to DMPA users of varying age or with obesity, endometriosis or HIV; four compared the safety of DMPA-SC and DMPA-IM when used by general populations of healthy women. A randomized trial evaluating changes in bone mineral density among adult DMPA-SC and DMPA-IM users demonstrated no differences at 2years of follow-up. Limited evidence reported no consistent differences in weight change or bleeding patterns according to age; however, adolescents (<18years) were not included in any studies. Similar contraceptive efficacy, weight change, bleeding patterns and occurrence of other adverse effects among obese and nonobese DMPA-SC users were observed. Women with endometriosis using DMPA-SC over 6months had minimal decreases in bone mineral density, weight gain, few serious adverse events and experienced improved pain symptoms. Women living with HIV tolerated injection of DMPA-SC with rare complications. DMPA-SC and DMPA-IM also show therapeutic equivalence and similar effects on weight gain, changes in bleeding patterns and reports of other adverse effects when these different delivery systems were used by general populations of women.
CONCLUSION
Evidence for use of DMPA-SC by women with select conditions and characteristics including age, obesity, endometriosis or HIV demonstrates that this method can generally be used safely in these contexts. Further, DMPA-SC and DMPA-IM appear to be therapeutically equivalent with similar safety profiles when used by healthy women.
Topics: Bone Density; Contraceptive Agents, Female; Delayed-Action Preparations; Endometriosis; Female; HIV Infections; Humans; Injections, Intramuscular; Injections, Subcutaneous; Medroxyprogesterone Acetate; Obesity; Pain; Patient Satisfaction; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Weight Gain; World Health Organization
PubMed: 26874275
DOI: 10.1016/j.contraception.2016.02.003 -
Breast Cancer Research and Treatment Jan 2016This systematic review summarizes research on the use of progestin and breast cancer risk. Although mainly used for contraception, progestin can help treat menstrual... (Meta-Analysis)
Meta-Analysis Review
This systematic review summarizes research on the use of progestin and breast cancer risk. Although mainly used for contraception, progestin can help treat menstrual disorders, and benign breast, uterine, and ovarian diseases. Breast cancer is the leading site of new, non-skin, cancers in females in the United States, and possible factors that may modulate breast cancer risk need to be identified. ProQuest (Ann Arbor, MI) and PubMed-Medline (US National Library of Medicine, Bethesda MD, USA) databases were used to search for epidemiologic studies from 2000 to 2015 that examined the association between progestin and breast cancer. Search terms included epidemiologic studies + progesterone or progestin or progestogen or contraceptive or contraceptive agents + breast cancer or breast neoplasms. A total of six studies were included in the review. Five of the six studies reported no association between progestin-only formulations (including norethindrone oral contraceptives, depot medroxyprogesterone acetate, injectable, levonorgestrel system users, implantable and intrauterine devices) and breast cancer risk. Duration of use was examined in a few studies with heterogeneous results. Unlike studies of other oral contraceptives, studies indicate that progestin-only formulations do not increase the risk of breast cancer, although the literature is hampered by small sample sizes. Future research is needed to corroborate these findings, as further understanding of synthetic progesterone may initiate new prescription practices or guidelines for women's health.
Topics: Breast Neoplasms; Contraceptive Agents, Female; Female; Humans; Levonorgestrel; Odds Ratio; Progestins; Risk
PubMed: 26700034
DOI: 10.1007/s10549-015-3663-1