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Climacteric : the Journal of the... Dec 2018The relationship between menopausal hormone therapy (HT) and breast cancer is complex and further complicated by misinformation, perception, and overgeneralization of... (Review)
Review
The relationship between menopausal hormone therapy (HT) and breast cancer is complex and further complicated by misinformation, perception, and overgeneralization of data. These issues are addressed in this mini-review through the lens of the Women's Health Initiative (WHI) that has colored the view of HT and breast cancer. In the WHI, unopposed conjugated equine estrogen (CEE) reduced breast cancer risk and mortality. In the WHI CEE plus continuously combined medroxyprogesterone acetate (MPA) trial, although the hazard ratio (HR) was elevated it was statistically non-significant for an association between CEE + MPA and breast cancer. In fact, the increased HR was not due to an increased breast cancer incidence rate in women randomized to CEE + MPA therapy but rather due to a decreased and unexpectedly low breast cancer rate in the subgroup of women with prior HT use randomized to placebo. For women who were HT naïve when randomized to the WHI, the breast cancer incidence rate was not affected by CEE + MPA therapy relative to placebo for up to 11 years of follow-up. The current state of science indicates that HT may or may not cause breast cancer but the totality of data neither establish nor refute this possibility. Further, any association that may exist between HT and breast cancer appears to be rare and no greater than other medications commonly used in clinical medicine.
Topics: Breast Neoplasms; Drug Therapy, Combination; Estrogens, Conjugated (USP); Female; Hormone Replacement Therapy; Humans; Medroxyprogesterone Acetate; Postmenopause; Randomized Controlled Trials as Topic
PubMed: 30296850
DOI: 10.1080/13697137.2018.1514008 -
Systematic Reviews Jul 2023Self-administered depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) is registered in many countries. It shows great potential for... (Review)
Review
BACKGROUND
Self-administered depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) is registered in many countries. It shows great potential for improving contraceptive access, continuation, and autonomy. However, there are challenges in rolling out this new efficacious intervention, and major implementation problems have been encountered during scale-up.
OBJECTIVE
To describe the implementation strategies to scale up self-administered DMPA-SC and the barriers, facilitators, and outcomes of these programs.
METHOD
Recent guidelines, including the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews, were used to design and report this review. An article or report was eligible for inclusion if it reported interventions that could scale up self-administered DMPA-SC implementation or its facilitators, barriers, or outcomes. We searched six electronic databases and the grey literature for eligible articles and reports. Two reviewers independently screened the document titles, abstracts, and full texts to identify eligible documents. Data were extracted using structured forms. Using the Effective Practice and Organization of Care (EPOC) taxonomy of health systems framework for thematic analysis, data were presented in a narrative approach.
RESULTS
Of the 755 retrieved documents, 34 were included in this review. Most of the documents included were multi-country reports (n = 14), and all documents were published within the last 5 years (2018-2021). This review identified documents that reported interventions in all EPOC domains. The most-reported interventions were: task-sharing amongst health workforce cadres, engaged leadership, encouraging policies, training and education, DMPA-SC demand generation, integration into existing programs, improved funding mechanisms, collaboration with development partners, and supply chain strengthening. The main barriers were suboptimal funding, inadequate human resources, and poor logistics supply of DMPA-SC. There was minimal evidence of scale-up outcomes.
CONCLUSION
This scoping review reported a wide range of interventions employed by countries and programs to scale up DMPA-SC self-administration but minimal evidence of the scale-up outcomes. Evidence from this review can help design better programs that improves access to quality family planning services to achieve the Sustainable Development Goals (SDG) targets 3.7. However, efforts should focus on rigorous implementation research that assess scaled up self-administered DMPA-SC interventions and report their outcomes.
REGISTRATION
The protocol for this review was registered in the protocols.io repository ( https://www.protocols.io/view/a-protocol-for-a-scoping-review-of-implementation-x54v9yemmg3e/v1 ).
Topics: Female; Humans; Contraception; Contraceptive Agents, Female; Injections, Subcutaneous; Medroxyprogesterone Acetate; Self Administration
PubMed: 37403147
DOI: 10.1186/s13643-023-02216-2 -
Life Sciences Jul 2023Medroxyprogesterone acetate (MPA) is the most common fertility-sparing treatment in patients with early-stage endometrial cancer. If MPA treatment fails, hysterectomy is...
AIMS
Medroxyprogesterone acetate (MPA) is the most common fertility-sparing treatment in patients with early-stage endometrial cancer. If MPA treatment fails, hysterectomy is recommended. Thus, there is an urgent need for novel treatment approaches for MPA-resistant endometrial cancer patients who wish to preserve their fertility. Ferroptosis is a recently discovered type of regulated cell death caused by the excessive accumulation of reactive oxygen species (ROS), followed by aberrant lipid peroxidation. Recent studies have shown that inducing ferroptosis is a potential therapeutic strategy for cancer. However, the role of ferroptosis in endometrial cancer treatment remains to be discussed. We therefore investigated the effects of ferroptosis inducers on MPA-resistant endometrial cancer cells.
MAIN METHODS
The levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), the main mediators of ferroptosis, were examined. Cell viability was evaluated after treatment with the ferroptosis inducers sulfasalazine, erastin, or RSL3. The degree of intracellular oxidative stress after treatment with these drugs was evaluated by the glutathione level, ROS level, ferrous iron level, lipid peroxidation and changes in mitochondrial morphology. The effect of ferroptosis inducers in vivo was also examined.
KEY FINDINGS
The expression of SLC7A11 and GPX4 in MPA-resistant ECC-1 cells decreased in comparison to parental ECC-1 cells. Sulfasalazine, erastin, and RSL3 significantly reduced cell viability and increased intracellular oxidative stress in MPA-resistant ECC-1 cells. Ferroptosis inducers also suppressed in vivo tumor growth more effectively in MPA-resistant ECC-1.
SIGNIFICANCE
Treatment with ferroptosis inducers could be a novel therapeutic approach for MPA-resistant endometrial cancer.
Topics: Female; Humans; Ferroptosis; Medroxyprogesterone Acetate; Reactive Oxygen Species; Sulfasalazine; Endometrial Neoplasms
PubMed: 37160245
DOI: 10.1016/j.lfs.2023.121753 -
Global Health, Science and Practice Nov 2014Provision of injectables though drug shops appears practicable and can contribute a marked share of family planning services. A potential longer-acting injectable...
Provision of injectables though drug shops appears practicable and can contribute a marked share of family planning services. A potential longer-acting injectable providing at least 6 months of protection appeals to programmatic professionals. Subcutaneous administration of DMPA offers major injectable improvements over the current intramuscular approach. Ironically, while injectable use will inevitably grow, better choice and wider availability of other methods—especially of long-acting and permanent methods—will reduce injectables′ overall share.
Topics: Contraception; Contraceptive Agents, Female; Family Planning Services; Female; Humans; Male; Medroxyprogesterone Acetate; Pharmaceutical Services
PubMed: 25611472
DOI: 10.9745/GHSP-D-14-00158 -
Epilepsy Research Dec 2017Reports on the reproductive health of women with epilepsy (WWE) in low- and middle-income countries (LMICs) are limited. Bhutan is a lower income country with a high...
INTRODUCTION
Reports on the reproductive health of women with epilepsy (WWE) in low- and middle-income countries (LMICs) are limited. Bhutan is a lower income country with a high estimated prevalence of epilepsy and no out-of-pocket payment requirements for health visits or medications.
METHODS
We developed a 10-category survey to interview WWE ages 20-59 years in the Kingdom of Bhutan to understand their contraceptive use and peripartum experiences. WWE were recruited from 2016-2017 from an existing epilepsy cohort and their reproductive health data were merged with epilepsy and socioeconomic data obtained from initial clinical evaluations performed between 2014 and 2016.
RESULTS
Of the 134 WWE eligible for the study, 94 were reachable and there was 1 refusal to participate (response rate 99% among reachable WWE; 69% of all WWE in the cohort). Of the 93 WWE (median age 27 years, range 20-52), 50 (54%) reported prior pregnancies. Of the entire cohort, 55 women responded on contraception: 26 (47%) WWE had never used contraception in their lifetime. Of the 29 WWE who had ever used contraception, the most commonly reported form was male condoms (14/29, 48%), followed by depot medroxyprogesterone acetate injections (13/29, 45%), and intrauterine devices (5/29, 17%). Sixty-three percent of WWE recalled receiving information on family planning (31 of 49). Of the 50 WWE with prior pregnancies, 37 of 46 (80%) used folic acid; 6 WWE reported commencing it in the first trimester while 29 WWE began supplementation in the second trimester. Primary school education or higher was associated with folic acid supplementation during pregnancy (26/29 vs. 11/17, p=0.040). Epilepsy affected at least one of the pregnancies in 38 of the cases (76%) with an average of 2.3 pregnancies per woman). There was a total of 86 pregnancies and an average inter-pregnancy interval of 3.5 years. Ninety-five percent of women attended prenatal care (36/38), 22% had at least one miscarriage (8/37), 14% had at least one pre-term delivery (5/36), and 21% had Caesarean sections (8/38). Seventeen of 38 (45%) of WWE had seizures during pregnancy. A majority of WWE (97%, 37 of 38) with a prior pregnancy reported breastfeeding their infant.
CONCLUSIONS
Nearly half of Bhutanese WWE did not use contraception; among those who used it, male condoms were most common but 11% were at risk of potential drug-drug interactions between oral contraception and enzyme-inducing antiepileptic drugs. Bhutanese WWE had a high rate of prenatal visits. Folic acid was prescribed in most pregnant WWE but the majority began supplementation in the second trimester. The number of pregnancies in WWE in Bhutan (2.3 per woman) was comparable to the number of children per women in Bhutan (2.3). Breastfeeding was practiced almost universally. Points of intervention may include pre-conception initiation of folic acid, optimization of dosing of AEDs with contraceptives, guidelines for peripartum seizure treatment, and establishment of a prospective registry for WWE and their offspring.
Topics: Adult; Age Factors; Bhutan; Contraception; Epilepsy; Female; Folic Acid; Health Surveys; Humans; Independent Living; Lactation; Medroxyprogesterone Acetate; Middle Aged; Peripartum Period; Pregnancy; Pregnancy Complications; PubMed; Young Adult
PubMed: 29128586
DOI: 10.1016/j.eplepsyres.2017.10.012 -
Fertility and Sterility Sep 2016Drugs for ovulation induction and exogenous hormones have been used since the 1960s.
Drugs for ovulation induction and exogenous hormones have been used since the 1960s.
Topics: Animals; Chorionic Gonadotropin; Clomiphene; Embryo Implantation; Female; Fertility; Fertility Agents, Female; Humans; Infertility; Medroxyprogesterone Acetate; Ovulation; Ovulation Induction; Pregnancy; Treatment Outcome; Uterine Contraction
PubMed: 27131299
DOI: 10.1016/j.fertnstert.2016.04.015 -
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 -
Sovremennye Tekhnologii V Meditsine 2021This review summarizes the current opinions on the mechanisms of action of nuclear, mitochondrial, and membrane progesterone receptors. The main aspects of the... (Review)
Review
This review summarizes the current opinions on the mechanisms of action of nuclear, mitochondrial, and membrane progesterone receptors. The main aspects of the pharmacological action of progestins have been studied. Data on the clinical use of gestagens by nosological groups are presented. Particular attention is paid to progesterone, megestrol acetate, medroxyprogesterone acetate due to broadening of their spectrum of action. The possibilities of using gestagens as neuroprotectors, immunomodulators, and chemosensitizers are considered.
Topics: Medroxyprogesterone; Medroxyprogesterone Acetate; Megestrol; Progesterone; Progestins
PubMed: 34513071
DOI: 10.17691/stm2021.13.1.11 -
Scientific Reports Jan 2023To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing...
To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokinetics, we collected serum and urine samples before COC ingestion and during Days one and three of use, or before DMPA injection and on Days 21 and 60 post-injection. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure serum/urine LNG and MPA. LNG was undetectable at baseline (specificity 100%); post ingestion, most urine samples had detectable LNG levels (sensitivity: 80% 6 h post Dose one, 93% 6 h post Dose three). We used a DetectX LNG immunoassay kit and showed 100% sensitivity measuring urine LNG. Urine MPA levels were undetectable in 14/15 women at baseline (specificity 91%); post-injection all urine samples had detectable MPA levels (sensitivity: 100% days 21 and 60). Results suggest urine sampling can be used to identify a biomarker of LNG and MPA use. Based on evidence from other steroidal hormonal studies showing changes affecting the transcriptome profile of saliva at 24 h, we used the same (COC, DMPA) timepoints to collect saliva. We performed transcriptome analysis and detected several differentially expressed genes in DMPA users' saliva on Days 21 and 60 compared to baseline; none among COC users. We plan further research of differential gene expression in saliva as a HC biomarker of DMPA use, and will explore longer periods of COC use and saliva collection times, and application of microRNA sequencing to support using saliva as a COC biomarker.
Topics: Female; Humans; Chromatography, Liquid; Pilot Projects; Tandem Mass Spectrometry; Levonorgestrel; Medroxyprogesterone Acetate; Contraceptives, Oral, Combined
PubMed: 36604469
DOI: 10.1038/s41598-022-24215-4 -
Depo-medroxyprogesterone acetate, weight gain and amenorrhea among obese adolescent and adult women.The European Journal of Contraception &... Feb 2020The aim of the study was to evaluate the correlation between obesity and the use of depot medroxyprogesterone (DMPA) with regard to weight gain and changes in bleeding...
The aim of the study was to evaluate the correlation between obesity and the use of depot medroxyprogesterone (DMPA) with regard to weight gain and changes in bleeding pattern. A retrospective chart review was conducted of women receiving 150 mg DMPA via intramuscular injection at inpatient and outpatient clinics at the University of Mississippi Medical Centre between 1 June 2012 and 31 December 2016. Body mass indices (BMI) were assessed at baseline and at the time of final injection. Data on race, medical history, age at first DMPA injection, number and timing of injections, reported side effects, indication for DMPA use and reason for discontinuation, if applicable, were collected. Of the 240 women included in the study, 3.3% were underweight, 30.8% were normal weight, 23.3% were overweight, 15% were class I obese, 9.6% were class II obese and 17.9% were class III obese; 87.9% of the population were African American. Women gained 2.40 kg (95% confidence interval 1.34-3.45) while they were on DMPA ( < .01), which after adjusting for confounding variables was inversely associated with age at initial injection ( coefficient -0.13; = .02). Amenorrhoea was the most commonly reported change in bleeding pattern. Women who started DMPA at an earlier age gained the most weight over time, independently of initial BMI. Similar rates of amenorrhoea were found among all BMI categories.
Topics: Adolescent; Adult; Age Factors; Amenorrhea; Body Mass Index; Contraceptive Agents, Female; Female; Humans; Injections, Intramuscular; Medroxyprogesterone Acetate; Obesity; Retrospective Studies; Time Factors; Weight Gain; Young Adult
PubMed: 31928370
DOI: 10.1080/13625187.2019.1709963