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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 -
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 -
Frontiers in Cellular and Infection... 2022Genital is the most common bacterial sexually transmitted infection in the United States and worldwide. Previous studies indicate that the progression of chlamydial...
Genital is the most common bacterial sexually transmitted infection in the United States and worldwide. Previous studies indicate that the progression of chlamydial infection is influenced by various factors, including the female sex hormones estrogen and progesterone. Sex hormone levels naturally fluctuate in women throughout their menstrual cycle. Varying concentrations of estrogen and progesterone may impact the progression of chlamydial infection and the host's immune response to . Estrogen signals through estrogen receptors (ERs), ERα and ERβ. These receptors are similar in structure and function, but are differentially expressed in tissues throughout the body, including the genital tract and on cells of the immune system. In this study, we used ovariectomized (OVT) BALB/c mice to investigate the impact of long-term administration of physiologically relevant concentrations of estrogen (E2), progesterone (P4), or a combination of E2/P4 on the progression of and immune response to infection. Additionally, we used ERα and ERβ knockout C57/BL6 mice to determine the how ERs affect chlamydial infection and the resulting immune response. Estrogen exposure prevented infection in vaginally infected OVT mice exposed to E2 alone or in combination with P4, while OVT or Sham mice exposed to hormone free, P4 or depo-medroxyprogesterone acetate shed similar amounts of chlamydiae. The hormonal environment also altered T cell recruitment and IFNϵ production the genital tracts of infected OVT and Sham mice on day 10 post infection. The absence of ERα, but not ERβ, in ER knockout mouse strains significantly changed the timing of infection. ERαKO mice shed significantly more chlamydiae at day 3 post infection and resolved the infection faster than WT or ERβKO animals. At day 9 post infection, flow cytometry showed that ERαKO mice had more T cells present and targeted RNA sequencing revealed increased expression of and , suggesting that ERαKO mice had increased numbers of regulatory T cells compared to ERβKO and WT mice. Mock and chlamydia-infected ERαKO mice also expressed more IFNϵ early during infection. Overall, the data from these studies indicate that sex hormones and their receptors, particularly ERα and ERβ, differentially affect infection in murine models of infection.
Topics: Animals; Female; Mice; Chlamydia Infections; Chlamydia muridarum; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens; Mice, Knockout; Progesterone
PubMed: 36636722
DOI: 10.3389/fcimb.2022.939944 -
PloS One 2023Progestin-only injectable contraceptives, mainly depo-medroxyprogesterone acetate intramuscular (DMPA-IM), are the most widely used contraceptive methods in sub-Saharan... (Randomized Controlled Trial)
Randomized Controlled Trial
Misreporting contraceptive use and the association of peak study progestin levels with weight and BMI among women randomized to the progestin-only injectable contraceptives DMPA-IM and NET-EN.
Progestin-only injectable contraceptives, mainly depo-medroxyprogesterone acetate intramuscular (DMPA-IM), are the most widely used contraceptive methods in sub-Saharan Africa. Insufficient robust data on their relative side-effects and serum concentrations limit understanding of reported outcomes in contraception trials. The WHICH clinical trial randomized HIV-negative women to DMPA-IM (n = 262) or norethisterone enanthate (NET-EN) (n = 259) at two South African sites between 2018-2019. We measured serum concentrations of study and non-study progestins at initiation (D0) and peak serum levels, one week after the 24-week injection [25 weeks (25W)], (n = 435) and investigated associations between study progestin levels, and BMI and weight of participants. Peak median serum concentrations were 6.59 (IQR 4.80; 8.70) nM for medroxyprogesterone (MPA) (n = 161) and 13.6 (IQR 9.01; 19.0) nM for norethisterone (NET) (n = 155). MPA was the most commonly quantifiable non-study progestin at D0 in both arms (54%) and at 25W in the NET-EN arm (27%), followed by NET at D0 in both arms (29%) and at 25W in the DMPA-IM arm (19%). Levonorgestrel was quantifiable in both arms [D0 (6.9%); 25W (3.4%)], while other progestins were quantifiable in ≤ 14 participants. Significant negative time-varying associations were detected between MPA and NET concentrations and weight and BMI in both contraceptive arms and a significant increase was detected for peak serum progestin concentrations for normal weight versus obese women. Contraceptive-related reported outcomes are likely confounded by MPA, more so than NET, with reported DMPA-IM effects likely underestimated, at sites where DMPA-IM is widely used, due to misreporting of contraceptive use before and during trials, and 'tail' effects of DMPA-IM use more than six months before trial enrolment. Peak serum levels of MPA and NET are negatively associated with BMI and weight, suggesting another source of variability between trial outcomes and a potential increase in side-effects for normal weight versus overweight and obese women. Trail registration: The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976).
Topics: Female; Humans; Progestins; Medroxyprogesterone Acetate; Contraceptive Agents; Body Mass Index; Norethindrone; Obesity
PubMed: 38134043
DOI: 10.1371/journal.pone.0295959 -
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 -
Obstetrics and Gynecology May 2021To examine the prevalence of contraindications to hormonal contraception among postpartum women.
OBJECTIVE
To examine the prevalence of contraindications to hormonal contraception among postpartum women.
METHODS
Low-income postpartum women who planned to delay childbearing for 2 years or longer after delivery were recruited for a prospective cohort study from eight Texas hospitals. Women self-reported health conditions that corresponded to category 3 and 4 contraindications to combined hormonal contraception and progestin-only methods, based on the Centers for Disease Control and Prevention's 2016 Medical Eligibility Criteria for Contraceptive Use. We used mixed-effects Poisson regression models to assess characteristics associated with reporting any contraindication 6 months after delivery. We examined the proportion of women who used a contraindicated method.
RESULTS
Of 1,452 women who completed the 6-month interview, 19.1% reported a category 3 or 4 contraindication to combined hormonal contraception (16.8% category 4) and 5.4% reported a contraindication to depot medroxyprogesterone acetate (0.1% category 4). Only 0.8% had any category 3 or 4 contraindication to progestin-only pills and 0.6% to the implant. Migraine with aura (12.4%) and hypertension (4.8%) were the most common contraindications. The prevalence of any contraindication was higher among women who were 30 years or older (prevalence ratio 1.45 95% CI 1.21-1.73), overweight (prevalence ratio 1.39, 95% CI 1.07-1.80), obese (prevalence ratio 1.55, 95% CI 1.16-2.07), and insured (prevalence ratio 1.34, 95% CI 1.04-1.74). Compared with U.S.-born Latina women, the prevalence of contraindications was higher among Black women (prevalence ratio 1.37, 95% CI 1.14-1.64) and lower among foreign-born Latina women (prevalence ratio 0.71, 95% CI 0.59-0.86). Among women with contraindications, 28 (10.3%) were using combined hormonal contraception; six (8%) were using a contraindicated progestin-only method.
CONCLUSION
Nearly one in five participants had a category 3 or 4 contraindication to combined hormonal contraception. Patients at higher risk for adverse birth outcomes are more likely to have contraindications. Clinicians should counsel on contraception and contraindications prenatally to facilitate the most informed postpartum decision.
Topics: Adult; Cohort Studies; Contraindications, Drug; Female; Hormonal Contraception; Humans; Postpartum Period; Pregnancy; Prevalence; Texas
PubMed: 33831931
DOI: 10.1097/AOG.0000000000004347 -
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 -
Translational Cancer Research Dec 2020Endometrial cancer (EC) is the most common cancer of the female reproductive system in developed countries. The incidence of EC has been increasing in young women.... (Review)
Review
Endometrial cancer (EC) is the most common cancer of the female reproductive system in developed countries. The incidence of EC has been increasing in young women. Approximately 4% of cases are aged <40 years. These young women may wish to delay therapy until after they have children. Common complaints in patients with EC include irregular vaginal bleeding, pelvic pain, and enlarged uterus. Imaging techniques such as transvaginal ultrasound (TVUS) or magnetic resonance imaging (MRI) can be utilized in detecting EC. Although the recommended treatment of EC is hysterectomy and bilateral salpingo-oophorectomy with or without systemic lymph node dissection, loss of reproductive function is the primary limiting factor of this surgical approach. Some studies have reported favorable results with high-dose oral progestins or levonorgestrel-releasing intrauterine system or hysteroscopic tumor resection followed by treatment with high-dose oral progestins. The most widely utilized medical treatment regimens are medroxyprogesterone acetate (MPA) 250-600 mg/day or megestrol acetate (MA) 160-480 mg/day. However, there is still a lack of evidence to establish the optimal dose and duration of progestin treatment. Patients with complete remission (CR) who wish to conceive must be encouraged, and referral to a fertility clinic should be offered as soon as possible. The key aspect of fertility-sparing management in women with EC appears to be the selection of appropriate candidates. Owing to the rarity of this condition, management may often be suboptimal. The aim of this review is to assess the current approaches to management of young women with EC who wish to preserve their fertility.
PubMed: 35117382
DOI: 10.21037/tcr-20-2232 -
Archives of Gynecology and Obstetrics Nov 2023Although many patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH) achieve complete remission (CR) after high-dose medroxyprogesterone acetate...
PURPOSE
Although many patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH) achieve complete remission (CR) after high-dose medroxyprogesterone acetate (MPA) treatment, no consensus has been reached on management after CR. Currently, patients receive estrogen-progestin maintenance therapy, but no recommendations exist regarding the duration of maintenance therapy or whether hysterectomy should be considered. This study aimed to provide insights into the management of EC/AEH after achieving CR.
METHODS
We retrospectively investigated the prognosis of 50 patients with EC or AEH who achieved CR after MPA therapy. We assessed the association between disease recurrence and clinicopathological features and the pre- and post-operative histological diagnoses of patients who underwent hysterectomy.
RESULTS
The median follow-up duration was 34 months (range: 1-179 months). Recurrence was observed in 17 patients. Among the clinical characteristics investigated, only the primary disease was significantly associated with disease recurrence; patients with EC had a higher risk of recurrence than those with AEH (p = 0.037). During the observation period, 27 patients attempted pregnancy, and 14 pregnancies resulted in delivery. Patients who gave birth had significantly longer relapse-free survivals than those who did not (p = 0.031). Further, 16 patients underwent hysterectomies, and AEH was detected postoperatively in 4 of 11 patients (36.4%) with no preoperative abnormalities.
CONCLUSIONS
We identified several clinical features of patients with EC and AEH after CR. Given the high probability of endometrial abnormalities detected postoperatively, hysterectomy may be considered for patients who no longer want children.
Topics: Pregnancy; Female; Child; Humans; Endometrial Hyperplasia; Retrospective Studies; Fertility Preservation; Treatment Outcome; Neoplasm Recurrence, Local; Endometrial Neoplasms; Medroxyprogesterone Acetate; Prognosis
PubMed: 37310452
DOI: 10.1007/s00404-023-07077-7