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Brain Research Jun 2013Both progesterone and estradiol have well-described neuroprotective effects against numerous insults in a variety of cell culture models, animal models and in humans.... (Review)
Review
Both progesterone and estradiol have well-described neuroprotective effects against numerous insults in a variety of cell culture models, animal models and in humans. However, the efficacy of these hormones may depend on a variety of factors, including the type of hormone used (ex. progesterone versus medroxyprogesterone acetate), the duration of the postmenopausal period prior to initiating the hormone intervention, and potentially, the age of the subject. The latter two factors relate to the proposed existence of a "window of therapeutic opportunity" for steroid hormones in the brain. While such a window of opportunity has been described for estrogen, there is a paucity of information to address whether such a window of opportunity exists for progesterone and its related progestins. Here, we review known cellular mechanisms likely to underlie the protective effects of progesterone and furthermore, describe key differences in the neurobiology of progesterone and the synthetic progestin, medroxyprogesterone acetate (MPA). Based on the latter, we offer a model that defines some of the key cellular and molecular players that predict the neuroprotective efficacy of progesterone. Accordingly, we suggest how changes in the expression or function of these cellular and molecular targets of progesterone with age or prolonged duration of hormone withdrawal (such as following surgical or natural menopause) may impact the efficacy of progesterone. This article is part of a Special Issue entitled Hormone Therapy.
Topics: Animals; Disease Models, Animal; Humans; Medroxyprogesterone Acetate; Nervous System Diseases; Neurons; Neuroprotective Agents; Predictive Value of Tests; Progesterone
PubMed: 23340161
DOI: 10.1016/j.brainres.2013.01.027 -
American Family Physician May 2014
Review
Topics: Adolescent; Adult; Contraceptive Agents, Female; Evidence-Based Medicine; Female; Humans; Medroxyprogesterone Acetate; Progestins; Weight Gain
PubMed: 24784333
DOI: No ID Found -
Canadian Family Physician Medecin de... Dec 2012
Topics: Female; Humans; Medroxyprogesterone Acetate; Progesterone; Progestins
PubMed: 23242886
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2008Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the... (Review)
Review
BACKGROUND
Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes.
OBJECTIVES
To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of combination injectable contraceptives.
SEARCH STRATEGY
We searched computerized databases for randomized controlled trials of combination injectable contraceptives.
SELECTION CRITERIA
Randomized controlled trials were eligible if they compared a combination injectable with any other contraceptive method (e.g., a second combination injectable contraceptive, progestin-only injectable contraceptive, other hormonal contraceptive or barrier method) or placebo. We limited the review to currently marketed combination injectable contraceptives.
DATA COLLECTION AND ANALYSIS
One author evaluated all titles and abstracts from the literature searches to determine their eligibility. Two authors independently extracted data from the eligible trials. Data on contraceptive efficacy, bleeding patterns, continuation, and side effects were entered and analyzed with RevMan.
MAIN RESULTS
Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5 mg. These contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems than progestin-only contraceptives. However, rates were higher for overall discontinuation and discontinuation due to other medical reasons. Acceptability results favored the combination injectable in one study and the progestin-only in another.Studies comparing two combination injectable contraceptives found that NET-EN 50 mg plus E(2)V 5 mg resulted in less overall discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials. The NET-EN plus E(2)V group also had more regular bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates.
AUTHORS' CONCLUSIONS
While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation depends on many factors. Future research should be directed toward interventions to improve the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinics, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.
Topics: Algestone; Contraception; Contraceptive Agents, Female; Drug Combinations; Estradiol; Female; Humans; Injections; Medication Adherence; Medroxyprogesterone; Megestrol Acetate; Norethindrone
PubMed: 18843662
DOI: 10.1002/14651858.CD004568.pub3 -
Thorax Jul 1999Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease occurring in women of reproductive age and leading to progressive respiratory failure in spite of treatment.... (Review)
Review
BACKGROUND
Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease occurring in women of reproductive age and leading to progressive respiratory failure in spite of treatment. In Korea the first case was reported in 1984 and by 1997 a total of 23 cases had been reported. The clinical findings of these Korean cases are reviewed.
METHODS
The details of 10 cases of LAM on file at Seoul National University Hospital were reviewed together with those of 13 cases previously reported from other Korean institutes. Two, including the only one to be reported in a man, were excluded after reviewing the clinical, radiological, and pathological findings, leaving a total of 21 cases in the present study.
RESULTS
All 21 patients were women and in all cases the disease was proven pathologically. The mean (SD) age at onset of symptoms was 32 (8.6) years. The most common symptoms were dyspnoea and pneumothorax which were seen in 19 (90%) and 13 (76%) patients, respectively. Pulmonary function tests showed decreased transfer factor (TLCO) (100%) and airflow limitation (67%). All the cases had characteristic cysts on high resolution computed tomographic (HRCT) scanning. The overall severity score based on HRCT scans correlated with the percentage predicted TLCO/VA (p = 0.03) and FEV1/FVC (p = 0.02). The patients were all treated with medroxyprogesterone and/or tamoxifen. Follow up was possible in 10 cases. Two of these patients appeared to stabilise with no appreciable change clinically or in lung function on medroxyprogesterone and/or tamoxifen, but the remaining patients all deteriorated with two dying of respiratory insufficiency and one of infection following lung transplantation.
CONCLUSIONS
As in other countries, in Korea LAM occurs exclusively in women and progresses despite hormonal treatment.
Topics: Adult; Age of Onset; Antineoplastic Agents, Hormonal; Female; Humans; Korea; Lung; Lung Neoplasms; Lymphangioleiomyomatosis; Medroxyprogesterone; Middle Aged; Radiography; Respiratory Function Tests; Tamoxifen
PubMed: 10377208
DOI: 10.1136/thx.54.7.618 -
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 -
Frontiers in Endocrinology 2021To compare the clinical outcomes of dydrogesterone (DYG) and medroxyprogesterone (MPA) in the progestin-primed ovarian stimulation (PPOS) protocol for patients with poor...
OBJECTIVE
To compare the clinical outcomes of dydrogesterone (DYG) and medroxyprogesterone (MPA) in the progestin-primed ovarian stimulation (PPOS) protocol for patients with poor ovarian response (POR).
PATIENTS AND METHODS
This was a retrospective cohort study. Women with POR who underwent IVF/ICSI at the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between January 2020 and January 2021 were included. The primary outcome measure of our study was the number of oocytes retrieved. The secondary outcome measures in the present study were the number of 2PN, number of available embryos, oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved, cancellation rate and pregnancy outcomes of the first embryo transfer cycle, including the biochemical pregnancy, clinical pregnancy and miscarriage rates.
RESULTS
In total, 118 women underwent hMG +DYG protocols, and 692 women who underwent hMG +MPA met the Bologna criteria for POR. After baseline characteristics were balanced using the PSM model, 118 hMG +DYG protocols were matched to 118 hMG +MPA protocols, and the baseline characteristics were comparable between the two groups. The numbers of oocytes retrieved, 2PN, and available embryos and the oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved and cancellation rate of the hMG+DYG and hMG+MPA protocols were comparable. Altogether, 66 women in the hMG+DYG group and 87 women in the hMG+MPA group underwent first embryo transfers. In the hMG+DYG group, 81.8% (54/66) of the patients underwent cleavage embryo transfers; similarly, 79.3% (69/87) of patients in the hMG+MPA group had cleavage embryo transfers (P=0.70).The biochemical pregnancy rate of the hMG+DYG group was 42.4%, and this was comparable to the rate in the hMG+DYG group, at 34.5% (P=0.32). The clinical pregnancy rates were similar between the two groups (36.4% 31.0%, P=0.49), and there was no significant difference in the rate of miscarriage between the two groups (12.5% 29.6%, P=0.14).
CONCLUSION
For women with POR, the clinical outcome of the hMG + DYG group was similar to that of the hMG + MPA group, indicating that both combinations can be useful options for PPOS protocols.
Topics: Adult; Contraceptives, Oral, Hormonal; Dydrogesterone; Female; Fertilization in Vitro; Follow-Up Studies; Humans; Infertility, Female; Medroxyprogesterone; Oocyte Retrieval; Oocytes; Ovulation Induction; Pregnancy; Pregnancy Outcome; Progestins; Prognosis; Retrospective Studies
PubMed: 34630325
DOI: 10.3389/fendo.2021.708704 -
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 -
Frontiers in Immunology 2020Depot Medroxyprogesterone (DMPA) is one of the most widely used contraceptives in Sub-Saharan Africa where HIV incidence is high. We explored the effect of DMPA on the...
BACKGROUND
Depot Medroxyprogesterone (DMPA) is one of the most widely used contraceptives in Sub-Saharan Africa where HIV incidence is high. We explored the effect of DMPA on the activation of HIV cellular targets and inflammation as a possible mechanism of increased HIV risk with DMPA use. Since sex work is known to affect the immune system, this study aimed to understand the effect of DMPA on the immune system among sex workers and non-sex worker women.
METHODS
Twenty-seven DMPA-using HIV seronegative female sex workers (FSW) and 30 DMPA-using HIV seronegative non-sex worker (SW) women were enrolled in the study. Twenty-four FSWs and 30 non-sex workers who were not using any hormonal contraception (no HC) were recruited as controls. Blood and cervico-vaginal samples were collected from all participants and assayed for T cell activation and proinflammatory cytokines.
RESULTS
Among no HC users, sex workers had lower expression of CD38 and CD69 on blood-derived CD4 T cells along with lower CD4CCR5 cells frequency in the endocervix. Plasma MCP-1, TNFα and IL-17 also had reduced expression in FSW not using HC. Non-sex workers using DMPA had elevated proportions of blood-derived CD4CD38, CD4CD69 and CD4HLA-DR T cells relative to non-sex workers who were not taking any HC. DMPA-using non-sex workers also had an increased level of plasma interferon gamma (IFN-), monokine induced by interferon- (MIG) and sCD40L, alongside higher proportion of CD4CD38 and CD4CD69 T cells at the cervix compared to non-sex workers no-HC controls., Finally, non-sex workers and FSWs using DMPA had similar levels of genital and peripheral CD4 T cell activation and inflammation.
CONCLUSION
DMPA increased inflammation and expression of activation markers on potential HIV target cells in non-sex workers. These data show that DMPA is a strong immune modulator and its use counteracts the decreased immune activation associated with sex work. These findings suggest that inflammation and increased HIV target cells in blood and at the genital tract may be mechanisms by which DMPA increases susceptibility to HIV.
Topics: Adolescent; Adult; Biomarkers; CD4-Positive T-Lymphocytes; Contraceptive Agents; Cytokines; Female; Humans; Immunophenotyping; Inflammation; Kenya; Lymphocyte Activation; Medroxyprogesterone; Mucous Membrane; Public Health Surveillance; Sex Workers; Young Adult
PubMed: 33717049
DOI: 10.3389/fimmu.2020.598307