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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 -
The Lancet. Diabetes & Endocrinology Aug 2020The validation of bone mineral density (BMD) as a surrogate outcome for fracture would allow the size of future randomised controlled osteoporosis registration trials to... (Meta-Analysis)
Meta-Analysis
Treatment-related changes in bone mineral density as a surrogate biomarker for fracture risk reduction: meta-regression analyses of individual patient data from multiple randomised controlled trials.
BACKGROUND
The validation of bone mineral density (BMD) as a surrogate outcome for fracture would allow the size of future randomised controlled osteoporosis registration trials to be reduced. We aimed to determine the association between treatment-related changes in BMD, assessed by dual-energy x-ray absorptiometry, and fracture outcomes, including the proportion of treatment effect explained by BMD changes.
METHODS
We did a pooled analysis of individual patient data from multiple randomised placebo-controlled clinical trials. We included data from multicentre, randomised, placebo-controlled, double-blind trials of osteoporosis medications that included women and men at increased osteoporotic fracture risk. Using individual patient data for each trial we calculated mean 24-month BMD percent change together with fracture reductions and did a meta-regression of the association between treatment-related differences in BMD changes (percentage difference, active minus placebo) and fracture risk reduction. We also used individual patient data to determine the proportion of anti-fracture treatment effect explained by BMD changes and the BMD change needed in future trials to ensure fracture reduction efficacy.
FINDINGS
Individual patient data from 91 779 participants of 23 randomised, placebo-controlled trials were included. The trials had 1-9 years of follow-up and included 12 trials of bisphosphonate, one of odanacatib, two of hormone therapy (one of conjugated equine oestrogen and one of conjugated equine oestrogen plus medroxyprogesterone acetate), three of PTH receptor agonists, one of denosumab, and four of selective oestrogen receptor modulator trials. The meta-regression revealed significant associations between treatment-related changes in hip, femoral neck, and spine BMD and reductions in vertebral (r 0·73, p<0·0001; 0·59, p=0·0005; 0·61, p=0·0003), hip (0·41, p=0·014; 0·41, p=0·0074; 0·34, p=0·023) and non-vertebral fractures (0·53, p=0·0021; 0·65, p<0·0001; 0·51, p=0·0019). Minimum 24-month percentage changes in total hip BMD providing almost certain fracture reductions in future trials ranged from 1·42% to 3·18%, depending on fracture site. Hip BMD changes explained substantial proportions (44-67%) of treatment-related fracture risk reduction.
INTERPRETATION
Treatment-related BMD changes are strongly associated with fracture reductions across randomised trials of osteoporosis therapies with differing mechanisms of action. These analyses support BMD as a surrogate outcome for fracture outcomes in future randomised trials of new osteoporosis therapies and provide an important demonstration of the value of public access to individual patient data from multiple trials.
FUNDING
Foundation for National Institutes of Health.
Topics: Absorptiometry, Photon; Biomarkers; Bone Density; Bone Density Conservation Agents; Data Interpretation, Statistical; Humans; Osteoporotic Fractures; Randomized Controlled Trials as Topic; Regression Analysis; Risk Reduction Behavior; Treatment Outcome
PubMed: 32707115
DOI: 10.1016/S2213-8587(20)30159-5 -
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 -
Clinical Endocrinology May 2021Antiandrogens are frequently used with estradiol in transgender women seeking feminization. Antiandrogens act by various mechanisms to decrease the production or effects... (Review)
Review
Antiandrogens are frequently used with estradiol in transgender women seeking feminization. Antiandrogens act by various mechanisms to decrease the production or effects of testosterone, but it is unclear which antiandrogen is most effective at feminization. A systematic review was performed using PRISMA guidelines. We searched online databases (Medline, Embase and PsycINFO) and references of relevant articles for studies of antiandrogens in transgender women aged 16+ years to achieve feminization (namely changes in breast size, body composition, facial or body hair) or changes in serum total testosterone concentration when compared to placebo, estradiol alone or an alternative antiandrogen. Four studies fulfilled eligibility criteria and were included in a narrative review. The addition of cyproterone acetate, leuprolide and medroxyprogesterone acetate may be more effective than spironolactone or estradiol alone at suppressing the serum total testosterone concentration. Body composition changes appear similar in transgender women treated with estradiol and additional cyproterone acetate or leuprolide. No eligible studies adequately evaluated the effects of antiandrogens on breast development or facial and body hair reduction. It remains unclear which antiandrogen is most effective at achieving feminization. Cyproterone acetate, medroxyprogesterone acetate and leuprolide may be more effective than spironolactone at suppressing the serum total testosterone concentration. However, due to spironolactone's antagonism of the androgen receptor, it is unclear whether this results in clinically meaningful differences in feminization. Further research with clinically meaningful endpoints is needed to optimize the use of antiandrogens in transgender women.
Topics: Androgen Antagonists; Cyproterone Acetate; Female; Feminization; Humans; Male; Transgender Persons; Transsexualism
PubMed: 32926454
DOI: 10.1111/cen.14329 -
Breastfeeding Medicine : the Official... Feb 2012Breastfeeding has numerous maternal and infant benefits. Progesterone contraception after birth is frequently recommended, but because a decrease in progesterone is... (Review)
Review
BACKGROUND
Breastfeeding has numerous maternal and infant benefits. Progesterone contraception after birth is frequently recommended, but because a decrease in progesterone is required to initiate lactation, early postpartum progesterone contraception use could inhibit lactation. The purpose of this article is to critically evaluate the scientific basis for conflicting clinical recommendations related to postpartum medroxyprogesterone use among breastfeeding women.
METHODS
Relevant peer-reviewed literature was identified through a comprehensive search of PubMed through December 2010. The search was restricted to clinical trials, randomized clinical trials, or comparative studies written in English and conducted among humans. The studies included in this review addressed the effect of medroxyprogesterone administration at <6 weeks postpartum on breastfeeding exclusivity and/or duration and measured breastfeeding outcomes at ≥ 6 weeks postpartum.
RESULTS
Of the 20 articles identified, only three studies satisfied the inclusion criteria. However, all three studies were of low-quality methodological rigor, and none accounted for potential confounders.
CONCLUSION
Current evidence is methodologically weak and provides an inadequate basis for inference about a possible causal relationship between early postpartum medroxyprogesterone use and poor breastfeeding outcomes. However, given the presence of a strong biological model describing the potential deleterious effect of postpartum medroxyprogesterone use on lactation, further research that improves on current literature is warranted. Meanwhile, we recommend that potential breastfeeding risks associated with early (<6 weeks) postpartum medroxyprogesterone use be disclosed to allow for a fully informed consent and decision-making process.
Topics: Breast Feeding; Contraceptives, Oral, Hormonal; Contraceptives, Oral, Synthetic; Decision Making; Evidence-Based Practice; Female; Humans; Infant, Newborn; Informed Consent; Lactation; Medroxyprogesterone Acetate; Mothers; Postpartum Period; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 22085201
DOI: 10.1089/bfm.2011.0105 -
Endocrine Practice : Official Journal... Dec 2022Transgender women take gender-affirming hormone therapy (GAHT) to affirm their gender identity and improve quality of life and well-being. Usually, GAHT in transgender... (Review)
Review
OBJECTIVE
Transgender women take gender-affirming hormone therapy (GAHT) to affirm their gender identity and improve quality of life and well-being. Usually, GAHT in transgender women consists of estrogen plus a testosterone-lowering medication. The use of progestogens in GAHT for transgender women has been a controversial topic due to lack of evidence for benefit and potential for increased harm.
METHODS
A systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using 4 databases (PubMed/MEDLINE, Ovid, and Cochrane). Manuscripts were reviewed from January 2000 to March 2022 to identify effects of progestogens in transgender women over the age of 16 years on breast development, cardiovascular disease, bone density, quality of life, and stroke incidence.
RESULTS
Ten articles were deemed eligible based on specific inclusion and exclusion criteria. Studies analyzing users of cyproterone acetate were also included if there was a comparator group. No relevant studies were found assessing stroke incidence in the transgender population using a progestogen compound.
CONCLUSION
Overall, findings were significant for a decreased high-density lipoprotein level and increased thromboembolism risk in transgender women using progestogens. No conclusive evidence was found regarding improved quality of life or breast development. Further research needs to be conducted assessing the effects of progestogens in transgender women.
Topics: Male; Female; Humans; Adolescent; Gender Identity; Progestins; Quality of Life
PubMed: 36007714
DOI: 10.1016/j.eprac.2022.08.012 -
BMJ Supportive & Palliative Care Mar 2021Randomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy... (Meta-Analysis)
Meta-Analysis
AIMS
Randomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy and safety are not available. We conducted a systematic review and network meta-analysis (NMA) to evaluate the relative efficacy and safety of pharmacological interventions for cachexia.
METHODS
PubMed, EmBase, Cochrane, and ClinicalTrials.gov were searched for RCTs until October 2019. Key outcomes were total body weight (TBW) improvement, appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias. NMA was performed to estimate weight gain and APP score increase at 8 weeks, presented as mean difference (MD) or standardised MD with 95% CI.
RESULTS
80 RCTs (10 579 patients) with 12 treatments were included. Majority is patients with cancer (7220). Compared with placebo, corticosteroids, high-dose megestrol acetate combination (Megace_H_Com) (400 mg/day), medroxyprogesterone, high-dose megestrol acetate (Megace_H) (400 mg/day), ghrelin mimetic and androgen analogues (Androgen) were significantly associated with MD of TBW of 6.45 (95% CI 2.45 to 10.45), 4.29 (95% CI 2.23 to 6.35), 3.18 (95% CI 0.94 to 5.41), 2.66 (95% CI 1.47 to 3.85), 1.73 (95% CI 0.27 to 3.20) and 1.50 (95% CI 0.56 to 2.44) kg. For appetite improvement, Megace_H_Com, Megace_H and Androgen significantly improved standardised APP score, compared with placebo. There is no significant difference in serious adverse events from all interventions compared with placebo.
CONCLUSIONS
Our findings suggest that several pharmacological interventions have potential to offer benefits in treatment of cachexia especially Megace_H and short-term use corticosteroids. Nonetheless, high-quality comparative studies to compare safety and efficacy are warranted for better management of cachexia.
Topics: Adrenal Cortex Hormones; Androgens; Appetite; Appetite Stimulants; Cachexia; Comparative Effectiveness Research; Drug Therapy, Combination; Gastrointestinal Agents; Ghrelin; Humans; Medroxyprogesterone; Megestrol Acetate; Minimal Clinically Important Difference; Neoplasms; Network Meta-Analysis; Randomized Controlled Trials as Topic; Terminal Care; Weight Gain
PubMed: 33246937
DOI: 10.1136/bmjspcare-2020-002601 -
Handbook of Experimental Pharmacology 2020Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone...
Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone acetate - DMPA), interfere with vitamin D levels (liver inducing anti-epileptic drugs), or directly by toxic effects on bone cells (chemotherapy, phenytoin, or thiazolidinedions, which diverts mesenchymal stem cells from forming osteoblasts to forming adipocytes). However, besides effects on the mineralized matrix, interactions with collagen and other parts of the unmineralized matrix may decrease bone biomechanical competence in a manner that may not correlate with bone mineral density (BMD) measured by dual energy absorptiometry (DXA).Some drugs and drug classes may decrease BMD like the thiazolidinediones and consequently increase fracture risk. Other drugs such as glucocorticoids may decrease BMD, and thus increase fracture risk. However, glucocorticoids may also interfere with the unmineralized matrix leading to an increase in fracture risk, not mirrored in BMD changes. Some drugs such as selective serotonin reuptake inhibitors (SSRI), paracetamol, and non-steroidal anti-inflammatory drugs (NSAIDs) may not per se be associated with bone loss, but fracture risk may be increased, possibly stemming from an increased risk of falls stemming from effects on postural balance mediated by effects on the central nervous system or cardiovascular system.This paper performs a systematic review of drugs inducing bone loss or associated with fracture risk. The chapter is organized by the Anatomical Therapeutic Chemical (ATC) classification.
Topics: Bone Density; Bone and Bones; Fractures, Bone; Humans; Medroxyprogesterone Acetate; Pharmaceutical Preparations
PubMed: 31889220
DOI: 10.1007/164_2019_340 -
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 -
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