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Endocrine Reviews Feb 2018Access to effective affordable contraception is critical for individual and public health. A wide range of hormonal contraceptives (HCs), which differ in composition,... (Review)
Review
Access to effective affordable contraception is critical for individual and public health. A wide range of hormonal contraceptives (HCs), which differ in composition, concentration of the progestin component, frequency of dosage, and method of administration, is currently available globally. However, the options are rather limited in settings with restricted economic resources that frequently overlap with areas of high HIV-1 prevalence. The predominant contraceptive used in sub-Saharan Africa is the progestin-only three-monthly injectable depot medroxyprogesterone acetate. Determination of whether HCs affect HIV-1 acquisition has been hampered by behavioral differences potentially confounding clinical observational data. Meta-analysis of these studies shows a significant association between depot medroxyprogesterone acetate use and increased risk of HIV-1 acquisition, raising important concerns. No association was found for combined oral contraceptives containing levonorgestrel, nor for the two-monthly injectable contraceptive norethisterone enanthate, although data for norethisterone enanthate are limited. Susceptibility to HIV-1 and other sexually transmitted infections may, however, be dependent on the type of progestin present in the formulation. Several underlying biological mechanisms that may mediate the effect of HCs on HIV-1 and other sexually transmitted infection acquisition have been identified in clinical, animal, and ex vivo studies. A substantial gap exists in the translation of basic research into clinical practice and public health policy. To bridge this gap, we review the current knowledge of underlying mechanisms and biological effects of commonly used progestins. The review sheds light on issues critical for an informed choice of progestins for the identification of safe, effective, acceptable, and affordable contraceptive methods.
Topics: Animals; Contraception; Contraceptive Agents, Female; Disease Susceptibility; Dose-Response Relationship, Drug; Female; Genitalia, Female; HIV Infections; HIV-1; Humans; Medroxyprogesterone Acetate; Progestins
PubMed: 29309550
DOI: 10.1210/er.2017-00103 -
Cureus Apr 2024Introduction In India, one of the world's most populous and swiftly growing countries, it is crucial to prioritize the utilization of safe and effective contraception,...
Introduction In India, one of the world's most populous and swiftly growing countries, it is crucial to prioritize the utilization of safe and effective contraception, as contraceptive strategies play a pivotal role in bolstering community health. It is widely acknowledged that ensuring appropriate timing and spacing of pregnancies is crucial for the well-being of reproductive, maternal, neonatal, child, and adolescent health. Adoption of reversible or spacing contraceptive methods can significantly enhance women's health outcomes by reducing the occurrence of undesired, closely timed, and mistimed pregnancies. Consequently, in response to the pressing need for dependable contraception in India, this study seeks to assess the acceptance, adherence, and side effects of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) among its users. Methods This prospective observational study was done at the State Government Taluk Hospital in the Cuddalore District of Tamil Nadu from July 2022 to October 2022. A total of 40 women of reproductive age who opted for DMPA as their contraceptive method and met the inclusion criteria were recruited through a purposive sampling method. A structured questionnaire was used to collect the data. Results The majority of the participants were women aged 21-25 years (n=14; 35%). The participants were predominantly Hindu (n=39; 97.5%), and 35 (87.5%) had completed higher secondary education. All participants (n=40; 100%) resided in rural areas and the majority were homemakers. A significant proportion of the participants had two children (n=21; 52.5%), and all of them received information on DMPA primarily from health personnel. At the initial point of data collection, three-fourths of them took the first dose (n=13; 32.5%) and only a few took more than three doses (n=3; 7.5%). In the third month, the results showed a drop in DMPA use, which indicates a lower adherence particularly linked to side effects like irregular bleeding (n=15; 37.5%) and amenorrhea (n=9; 22.5%). Furthermore, 35 (87.5%) of the women chose DMPA for birth spacing due to its efficacy and convenience, with few initiating it during postpartum (n=4; 10%) and post-abortal (n=1; 2.5%) periods. The reasons for continuing DMPA use included efficacy (n=20; 50%), discreet usage (n=15; 37.5%), and curiosity (n=13; 32.5%). Half of the participants reported no side effects. The study identified associations between DMPA users and the number of living children and occupational status inferring that DMPA contraception is used for spacing births. Conclusion The results of this study imply that the use and adherence to injectable contraceptive DMPA need to be strengthened among rural women. Thus, the study suggests incorporating information, education, and communication strategies, to enhance awareness among rural women about injectable contraceptives.
PubMed: 38779259
DOI: 10.7759/cureus.58700 -
British Journal of Cancer Sep 2023The effectiveness of conservative treatment of endometrial carcinoma (EC) with oral progesterone therapy, such as medroxyprogesterone acetate (MPA), can be blunted due...
BACKGROUND
The effectiveness of conservative treatment of endometrial carcinoma (EC) with oral progesterone therapy, such as medroxyprogesterone acetate (MPA), can be blunted due to primary or acquired resistance, but the underlying mechanisms remain incompletely defined.
METHODS
Genome-wide CRISPR screening was performed to identify potential regulators in response to MPA in Ishikawa cells. Crystal violet staining, RT-qPCR, western blotting, ChIP-qPCR and luciferase assays were employed to elucidate the p53-AarF domain-containing kinase 3 (ADCK3) regulatory axis and its roles in sensitizing EC cells to MPA treatment.
RESULTS
ADCK3 is identified as a previously unrecognized regulator in response to MPA in EC cells. Loss of ADCK3 in EC cells markedly alleviated MPA-induced cell death. Mechanistically, loss of ADCK3 primarily suppresses MPA-mediated ferroptosis by abrogating arachidonate 15-lipoxygenase (ALOX15) transcriptional activation. Moreover, we validated ADCK3 as a direct downstream target of the tumor suppressor p53 in EC cells. By stimulating the p53-ADCK3 axis, the small-molecule compound Nutlin3A synergized with MPA to efficiently inhibit EC cell growth.
CONCLUSIONS
Our findings reveal ADCK3 as a key regulator of EC cells in response to MPA and shed light on a potential strategy for conservative EC treatment by activating the p53-ADCK3 axis to sensitize MPA-mediated cell death.
Topics: Female; Humans; Medroxyprogesterone Acetate; Tumor Suppressor Protein p53; Clustered Regularly Interspaced Short Palindromic Repeats; Endometrial Neoplasms; Cell Line, Tumor
PubMed: 37402867
DOI: 10.1038/s41416-023-02347-2 -
Molecular and Cellular Endocrinology Mar 2023The pro-inflammatory cytokine, chemokine (C-C motif) ligand 20 (CCL20), is emerging as a therapeutic target for immune-based therapies. Cooperative regulation of CCL20...
The pro-inflammatory cytokine, chemokine (C-C motif) ligand 20 (CCL20), is emerging as a therapeutic target for immune-based therapies. Cooperative regulation of CCL20 by glucocorticoids and progestins used in endocrine therapy and pro-inflammatory mediators could modulate immune function and affect disease outcomes. We show that glucocorticoids as well as medroxyprogesterone acetate (MPA), the progestin widely used in injectable contraception in sub-Saharan Africa, cooperate with pro-inflammatory mediators to upregulate CCL20 protein and/or mRNA in human peripheral blood mononuclear cells (PBMCs) and human cervical cell lines. Changes in CCL20 mRNA levels were shown to be synergistic, as assessed by Chou analysis, cell- and gene-specific and to involve transcriptional regulation, with a requirement for a nuclear factor kappa B (NF-κB) site and glucocorticoid receptor (GR) involvement. The novel results suggest a mechanism whereby MPA, like glucocorticoids, may impact inflammation both systemically and in the genital tract in patients using MPA and/or glucocorticoid therapy.
Topics: Humans; Medroxyprogesterone Acetate; Glucocorticoids; Leukocytes, Mononuclear; Progestins; Receptors, Glucocorticoid; RNA, Messenger; Chemokine CCL20
PubMed: 36646303
DOI: 10.1016/j.mce.2023.111855 -
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 Mar 2018DMPA-SC is a contraceptive injectable formulation that provides women and couples another important voluntary family planning option. It offers characteristics that many...
DMPA-SC is a contraceptive injectable formulation that provides women and couples another important voluntary family planning option. It offers characteristics that many women like, including cost and time savings, and has the potential to be delivered by a range of health care cadres in a variety of service delivery channels.
Topics: Contraception; Contraceptive Agents; Contraceptive Agents, Female; Humans; Injections; Medroxyprogesterone Acetate
PubMed: 29602863
DOI: 10.9745/GHSP-D-18-00050 -
Cleveland Clinic Journal of Medicine Dec 2021Long-acting reversible contraceptives (ie, intrauterine devices and the etonogestrel subdermal implant) have become increasingly popular methods of contraception because...
Long-acting reversible contraceptives (ie, intrauterine devices and the etonogestrel subdermal implant) have become increasingly popular methods of contraception because of their convenience and safety profile. At the same time, the use of depot medroxyprogesterone acetate, one of the most prescribed contraceptives in the United States since its approval in 1992, is on the wane. The history and pros and cons of these contraceptive methods are reviewed.
Topics: Contraception; Contraceptive Agents, Female; Female; Humans; Intrauterine Devices; Medroxyprogesterone Acetate; United States
PubMed: 34857607
DOI: 10.3949/ccjm.88a.20110 -
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 -
BMJ Global Health Jul 2022Subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is an innovative contraceptive method aimed at meeting women's unique circumstances and needs, largely due to... (Review)
Review
Subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is an innovative contraceptive method aimed at meeting women's unique circumstances and needs, largely due to its ability to be self-injected. Substantial research and advocacy investments have been made to promote roll-out of DMPA-SC across sub-Saharan Africa. To date, research on the demand for DMPA-SC as a self-injectable method has been conducted largely with healthcare providers, via qualitative research, or with highly specific subsamples that are not population based. Using three recent rounds of data from Performance Monitoring for Action, we examined population-representative trends in demand, use, and preference for self-injection among current non-users in Burkina Faso, the Democratic Republic of Congo (Kinshasa and Kongo Central regions), Kenya, and Nigeria (Lagos and Kano States). We found that while over 80.0% of women had heard of injectables across settings, few women had heard of self-injection (ranging from 13.0% in Kenya to 24.8% in Burkina Faso). Despite initial increases in DMPA-SC prevalence, DMPA-SC usage began to stagnate or even decrease in all settings in the recent three years (except in Nigeria-Kano). Few (0.0%-16.7%) current DMPA-SC users were self-injecting, and the majority instead were relying on a healthcare provider for administration of DMPA-SC. Among current contraceptive non-users wishing to use an injectable in the future, only 1.5%-11.4% preferred to self-inject. Our results show that self-injection is uncommon, and demand for self-injection is very limited across six settings, calling for further qualitative and quantitative research on women's views on DMPA-SC and self-injection and, ultimately, their contraceptive preferences and needs.
Topics: Contraceptive Agents, Female; Democratic Republic of the Congo; Female; Humans; Injections, Subcutaneous; Medroxyprogesterone Acetate; Nigeria; Self Administration
PubMed: 35835480
DOI: 10.1136/bmjgh-2022-008862 -
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