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Hematology. American Society of... Dec 2022Estrogen exposure, in the setting of pregnancy, the postpartum state, combined hormonal contraceptives (CHCs), or hormone therapy use, has been clearly associated with...
Estrogen exposure, in the setting of pregnancy, the postpartum state, combined hormonal contraceptives (CHCs), or hormone therapy use, has been clearly associated with increased rates of venous thromboembolism (VTE). Although recurrence rates are low in these settings, up to 70% of anticoagulated menstruating individuals experience abnormal or heavy menstrual bleeding (HMB), which commonly results in iron deficiency with or without anemia. Patients taking rivaroxaban appear to experience higher rates of HMB compared with those on apixaban, dabigatran, or warfarin. HMB can often be diagnosed in a single visit with a good menstrual history assessing for factors with a known association with increased or heavy bleeding, such as changing pads or tampons more often than every 2 hours, clots larger than a quarter, and iron deficiency (ferritin <50 ng/mL). HMB can be managed with hormonal therapies, including those associated with VTE risk, such as CHCs and depot-medroxyprogesterone acetate (DMPA). In many cases, continuing CHCs or DMPA while a patient is therapeutically anticoagulated is reasonable, so long as the therapy is discontinued before anticoagulation is stopped. Modification of the anticoagulation regimen, such as decreasing to a prophylactic dose in the acute treatment period, is not currently recommended. For patients who are currently pregnant, low-molecular-weight heparin (LMWH) is still standard of care during pregnancy; routine monitoring of anti-factor Xa levels is not currently recommended. Warfarin or LMWH may be considered in the postpartum setting, but direct-acting oral anticoagulants are currently not recommended for lactating patients.
Topics: Pregnancy; Humans; Female; Heparin, Low-Molecular-Weight; Lactation; Anticoagulants; Venous Thromboembolism; Warfarin; Menorrhagia; Iron Deficiencies
PubMed: 36485151
DOI: 10.1182/hematology.2022000401 -
Frontiers in Endocrinology 2023To explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone...
The comparison between fixed versus degressive doses of medroxyprogesterone acetate combined with letrozole in patients of progestin-primed ovarian stimulation protocol: a propensity score-matched study.
OBJECTIVE
To explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women by propensity score matching (PSM) analysis.
DESIGN
A retrospective cohort study.
SETTING
Tertiary-care academic medical center.
POPULATION
A total of 3173 infertile women undergoing their first fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment within the period from January 2017 to December 2020.
METHODS
A total of 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively, were enrolled in this study. The freeze-all approach and later frozen-thawed embryo transfer (FET) were performed in both groups. Propensity score matching (1:1) was performed.
MAIN OUTCOME MEASURES
The primary outcomes were the dosage of MPA and the incidence of premature luteinizing hormone (LH) surges. The secondary outcomes were the number of oocytes retrieved, the cumulative live birth rate (CLBR) and the fetal malformation rate.
RESULTS
We created a perfect match of 478 patients in each group. The dosage of MPA, the LH serum level on the eighth day of stimulation, progesterone (P) level and LH level on the hCG trigger day were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group (52.1 ± 13.1 mg vs. 44.9 ± 12.5 mg; 5.0 ± 2.7 IU/L vs. 3.7 ± 1.7 IU/L; 0.9 ± 0.5 ng/ml vs. 0.8 ± 0.5 ng/ml; 3.3 ± 2.4 IU/L vs. 2.8 ± 1.9 IU/L; < 0.01). The duration of Gn, the number of follicles with diameter more than 16 mm on trigger day, the estradiol (E) level on the hCG trigger day were lower in the LE + fixed MPA group than in the LE + degressive MPA group (9.7 ± 1.7 days vs. 10.3 ± 1.5 days; 5.6 ± 3.0 vs. 6.3 ± 3.0; 1752.5 ± 1120.8 pg/ml vs. 1997.2 ± 1108.5 pg/ml; < 0.001). No significant difference was found in the incidence of premature LH surge, the number of oocytes retrieved, the number of top-quality embryos, clinical pregnancy rate (CPR), CLBR or fetal malformation rate between the two groups.
CONCLUSION
The combination of a degressive MPA dose with LE proved effective in reducing the total MPA dosage with comparable premature LH surge and pregnancy outcomes in women undergoing the PPOS protocol.
Topics: Pregnancy; Humans; Female; Male; Progestins; Medroxyprogesterone Acetate; Letrozole; Infertility, Female; Retrospective Studies; Propensity Score; Semen; Ovulation Induction; Luteinizing Hormone
PubMed: 38155955
DOI: 10.3389/fendo.2023.1295787 -
Medical Archives (Sarajevo, Bosnia and... 2023Depot medroxyprogesterone acetate (DMPA) is a progesterone derivative synthesized in the laboratory. This substance has the ability to suppress ovulation, induce...
BACKGROUND
Depot medroxyprogesterone acetate (DMPA) is a progesterone derivative synthesized in the laboratory. This substance has the ability to suppress ovulation, induce endometrial shrinkage, and even affect the hypothalamic-pituitary-gonadal axis in the reproductive system.
OBJECTIVE
The purpose of this study was to investigate the effects of administration of green tea extract on reducing visceral fat, increasing leptin levels, and improving the lipid profile in female rats injected with depot medroxyprogesterone acetate (DMPA).
RESULTS
This study was to look into the effects of green tea extract administration on visceral fat reduction, leptin levels, and lipid profile improvement as a result of DMPA administration. Analysis of HDL and LDL levels was performed by spectrophotometry. DMPA induced a significant increase in leptin levels compared with the control group (p 0.05). All doses of green tea extract can reduce this increase, with the highest doses reaching levels comparable to the control group ( > 0.05). DMPA significantly increased LDL levels compared to the control group ( < 0.05), and the highest green tea extract dose restored levels similar to the control group. DMPA triggered a decrease in HDL level that was significantly different from the control group ( < 0.05). The first dose of green tea extract can achieve HDL levels comparable to the control group ( > 0.05).
CONCLUSION
It was concluded that green tea extract can protect the metabolic status through decreased leptin and an improvement of the lipid profile induced by DMPA.
Topics: Female; Animals; Rats; Leptin; Medroxyprogesterone Acetate; Antioxidants; Tea; Lipids
PubMed: 37700918
DOI: 10.5455/medarh.2023.77.173-177 -
Clinical and Experimental Reproductive... Dec 2020Endometrial cancer (EC) in young women tends to be early-stage and low-grade; therefore, such cases have good prognoses. Fertility-sparing treatment with progestin is a...
Endometrial cancer (EC) in young women tends to be early-stage and low-grade; therefore, such cases have good prognoses. Fertility-sparing treatment with progestin is a potential alternative to definitive treatment (i.e., total hysterectomy, bilateral salpingo-oophorectomy, pelvic washing, and/or lymphadenectomy) for selected patients. However, no evidence-based consensus or guidelines yet exist, and this topic is subject to much debate. Generally, the ideal candidates for fertility-sparing treatment have been suggested to be young women with grade 1 endometrioid adenocarcinoma confined to the endometrium. Magnetic resonance imaging should be performed to rule out myometrial invasion and extrauterine disease before initiating fertility-sparing treatment. Although various fertility-sparing treatment methods exist, including the levonorgestrel-intrauterine system, metformin, gonadotropin-releasing hormone agonists, photodynamic therapy, and hysteroscopic resection, the most common method is high-dose oral progestin (medroxyprogesterone acetate at 500-600 mg daily or megestrol acetate at 160 mg daily). During treatment, re-evaluation of the endometrium with dilation and curettage at 3 months is recommended. Although no consensus exists regarding the ideal duration of maintenance treatment after achieving regression, it is reasonable to consider maintaining the progestin therapy until pregnancy with individualization. According to the literature, the ovarian stimulation drugs used for fertility treatments appear safe. Hysterectomy should be performed after childbearing, and hysterectomy without oophorectomy can also be considered for young women. The available evidence suggests that fertility-sparing treatment is effective and does not appear to worsen the prognosis. If an eligible patient strongly desires fertility despite the risk of recurrence, the clinician should consider fertility-sparing treatment with close follow-up.
PubMed: 33181010
DOI: 10.5653/cerm.2020.03629 -
Environmental Research Jan 2022Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in commercial and consumer goods. Black women are underrepresented in studies of PFAS exposure.
BACKGROUND
Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in commercial and consumer goods. Black women are underrepresented in studies of PFAS exposure.
METHODS
We performed a cross-sectional analysis of correlates of plasma PFAS concentrations among 1499 Black women aged 23-35 participating in the Study of Environment, Lifestyle, and Fibroids (SELF), a Detroit-based cohort study. At baseline (2010-2012), participants provided questionnaire data on socio-demographics; behaviors; diet; and menstrual, contraceptive, and reproductive histories. Using mass spectrometry in non-fasting plasma samples collected at enrollment, we quantified several PFAS, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA). We used linear regression to calculate percentage differences (%D) and 95 % confidence intervals (CIs) for associations between selected correlates and PFAS concentrations, adjusting for all other correlates.
RESULTS
PFHxS, PFOS, PFOA, and PFNA were detected in ≥97 % of women; PFDA in 86 %; MeFOSAA in 70 %; and PFUnDA in 52 %. Age, income, education, and intakes of water, alcohol, and seafood were positively associated with several PFAS. Current smoking was positively associated with MeFOSAA. Body mass index was inversely associated with most PFAS, except PFHxS. Strong inverse associations (%D; 95 % CI) were observed between parity (≥3 vs. 0 births) and PFHxS (-34.7; -43.0, -25.1) and PFOA (-33.1; -39.2, -26.3); breastfeeding duration (≥6 months vs. nulliparous) and PFOA (-31.1; -37.8, -23.7), PFHxS (-24.2; -34.5, -12.3), and PFOS (-18.4; -28.3, -7.1); recent birth (<2 years ago vs. nulliparous) and PFOA (-33.1; -39.6, -25.8), PFHxS (-29.3; -39.0, -18.1), PFNA (-25.2; -32.7, -16.8), and PFOS (-18.3; -28.3, -6.9); and intensity of menstrual bleed (heavy vs. light) and PFHxS (-18.8; -28.3, -8.2), PFOS (-16.4; -24.9, -7.1), PFNA (-10.5; -17.8, -2.6), and PFOA (-10.0; -17.2, -2.1). Current use of depot medroxyprogesterone acetate (DMPA) was positively associated with PFOS (20.2; 1.4, 42.5), PFOA (16.2; 1.5, 33.0), and PFNA (15.3; 0.4, 32.4).
CONCLUSIONS
Reproductive factors that influence PFAS elimination showed strong associations with several PFAS (reduced concentrations with parity, recent birth, lactation, heavy menstrual bleeding; increased concentrations with DMPA use).
Topics: Adult; Alkanesulfonic Acids; Cohort Studies; Cross-Sectional Studies; Diet; Environmental Pollutants; Female; Fluorocarbons; Humans; Pregnancy; Reproduction
PubMed: 34403666
DOI: 10.1016/j.envres.2021.111860 -
Journal of Gynecologic Oncology Jul 2023To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial cancer (EC) following initial fertility-sparing treatment.
METHODS
A comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Endometrial Cancer Committee. Multiple search engines, including PubMed/MEDLINE and the Cochrane Database, were searched in December 2021 using the keywords "Endometrial neoplasms," "Endometrial hyperplasia," "Endometrial intraepithelial neoplasia," "Fertility preservation," "Progestins," AND "Recurrence." Cases describing progestin re-treatment for recurrent EIN, AH and EC were compared with cases that underwent conventional hysterectomy. The primary outcomes were survival and disease recurrence, and the secondary outcome was pregnancy.
RESULTS
After screening 238 studies, 32 with results for recurrent treatment were identified. These studies included 365 patients (270 received progestin re-treatment and 95 underwent hysterectomy). Most progestin re-treatment involved medroxyprogesterone acetate or megestrol acetate (94.5%). Complete remission (CR) following progestin re-treatment was achieved in 219 (81.1%) cases, with 3-, 6- and 9-month cumulative CR rates of 22.8%, 51.7% and 82.6%, respectively. Progestin re-treatment was associated with higher risk of disease recurrence than conventional hysterectomy was (odds ratio [OR]=6.78; 95% confidence interval [CI]=1.99-23.10), and one patient (0.4%) died of disease. Fifty-one (14.0%) women became pregnant after recurrence, and progestin re-treatment demonstrated a possibility of pregnancy (OR=2.48; 95% CI=0.94-6.58).
CONCLUSION
This meta-analysis suggests that repeat progestin therapy is an effective option for women with recurrent EIN, AH and EC, who wish to retain their fertility.
Topics: Pregnancy; Female; Humans; Endometrial Hyperplasia; Progestins; Retrospective Studies; Neoplasm Recurrence, Local; Endometrial Neoplasms; Fertility Preservation; Treatment Outcome
PubMed: 36929578
DOI: 10.3802/jgo.2023.34.e49 -
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 -
BMC Medical Genomics Nov 2019Progestin is effective to promote endometrial cancer (EC) cells apoptosis, however, continuous progestin administration causes low level of progestin receptor B (PRB),...
BACKGROUND
Progestin is effective to promote endometrial cancer (EC) cells apoptosis, however, continuous progestin administration causes low level of progestin receptor B (PRB), further resulting in progestin resistance. Here, we performed microarray analysis on Ishikawa cells (PRB+) treated with medroxyprogesterone acetate (MPA) to explore the molecular mechanism underlying the inhibitory influence of MPA on PRB+ EC cells.
METHODS
Microarray analysis was performed by using Ishikawa cells (PRB+) treated with MPA. Differentially expressed mRNA and long noncoding RNAs (lncRNAs) were identified. Furthermore, the functions of these mRNAs and lncRNAs were predicted by functional enrichment analysis. QRT-PCR was further performed to verify the microarray data.
RESULTS
A total of 358 differentially expressed genes and 292 lncRNAs were identified in Ishikawa cells (PRB+) treated with MPA. QRT-PCR verified these data. Functional enrichment analysis identified endoplasmic reticulum (ER) stress as the key pathway involved in the inhibitory effect of MPA on EC cells. And the ER stress apoptotic molecule CHOP and ER stress related molecule HERPUD1 were both highly expressed in Ishikawa cells (PRB+) treated with MPA. Co-expression analysis showed lnc-CETP-3 was highly correlated with CHOP and HERPUD1, suggesting it might participate in ER stress pathway-related EC cell apoptosis caused by MPA. In addition, compared with untreated cells, lnc-CETP-3, CHOP and HERPUD1 were significantly up-regulated in Ishikawa cells (PRB+) treated with MPA, whereas they have no statistical significance in KLE cells (PRB-).
CONCLUSIONS
MPA may activate ER stress by progesterone-PRB pathway to up-regulate CHOP expression, which may be one of the molecular mechanisms underlying the inhibitory effect of MPA on EC cells with PRB+. Lnc-CETP-3 might be involved in this process. These findings may provide therapeutic targets for EC patients with PRB-, and resistance-related targets to increase the sensitivity of MPA on EC cells.
Topics: Apoptosis; Cell Line, Tumor; Contraceptive Agents, Hormonal; Endometrial Neoplasms; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Female; Gene Expression Regulation, Neoplastic; Humans; Medroxyprogesterone Acetate; Membrane Proteins; RNA, Long Noncoding; RNA, Messenger; Receptors, Progesterone; Transcription Factor CHOP
PubMed: 31718641
DOI: 10.1186/s12920-019-0601-9 -
BMJ Open Feb 2020Progestin therapy is the only fertility-sparing treatment option for patients with atypical endometrial hyperplasia (AEH) and endometrial cancer (EC). However, the... (Randomized Controlled Trial)
Randomized Controlled Trial
Medroxyprogesterone acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and endometrial carcinoma: trial protocol for a prospective, randomised, open, blinded-endpoint design, dose-response trial (FELICIA trial).
INTRODUCTION
Progestin therapy is the only fertility-sparing treatment option for patients with atypical endometrial hyperplasia (AEH) and endometrial cancer (EC). However, the results of three meta-analyses revealed a high remission rate, as well as an association with a high rate of relapse. We previously conducted a phase II of medroxyprogesterone acetate (MPA) plus metformin as a fertility-sparing treatment for AEH and EC patients, and reported that metformin inhibited disease relapse after remission.
METHODS AND ANALYSIS
A randomised, open, blinded-endpoint design phase IIb dose response trial was planned to commence in July 2019. The trial aims to identify the appropriate dose of metformin to be combined with MPA therapy for fertilitysparing treatment of patients with AEH and EC. The primary endpoint of the trial is the 3-year relapse-free survival (RFS) rate. The secondary endpoints are RFS rate, the overall rate of response to MPA therapy, the conception rate after treatment, the outcome of pregnancy, toxicity evaluation and changes in insulin resistance and body mass index. A total of 120 patients will be enrolled from 15 Japanese institutions within a 2.5-year period and followed up for at least 3 years.
ETHICS AND DISSEMINATION
The protocol was approved by the institutional review board at Chiba University Hospital and boards at 14 other institutions. The trial will be conducted according to the principles of the World Medical Association's Declaration of Helsinki and in accordance with Good Clinical Practice (GCP) standards. The trial findings will be published in a peer-reviewed journal.
TRIAL REGISTRATION NUMBER
Japan Registry of Clinical Trials (jRCT2031190065).
Topics: Adult; Antineoplastic Agents, Hormonal; Clinical Protocols; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Therapy, Combination; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Follow-Up Studies; Humans; Hypoglycemic Agents; Medroxyprogesterone Acetate; Metformin; Proportional Hazards Models; Prospective Studies; Single-Blind Method; Treatment Outcome
PubMed: 32114477
DOI: 10.1136/bmjopen-2019-035416 -
Clinical Infectious Diseases : An... Jul 2020Effective contraception is critical to young women with HIV-associated tuberculosis (TB), as unintended pregnancy is associated with increased perinatal morbidity and...
Pharmacokinetics and Pharmacodynamics of Depot Medroxyprogesterone Acetate in African Women Receiving Treatment for Human Immunodeficiency Virus and Tuberculosis: Potential Concern for Standard Dosing Frequency.
BACKGROUND
Effective contraception is critical to young women with HIV-associated tuberculosis (TB), as unintended pregnancy is associated with increased perinatal morbidity and mortality. The effects of co-administration of efavirenz and rifampicin on the pharmacokinetics of depot medroxyprogesterone acetate (DMPA) are unknown. We hypothesized that clearance of medroxyprogesterone acetate (MPA) would increase when given with rifampicin and efavirenz, thus increasing risk of ovulation.
METHODS
This pharmacokinetics (PK) study assessed DMPA among HIV/TB coinfected women on an efavirenz-based antiretroviral treatment and rifampicin-based TB treatment. Plasma MPA concentrations and progesterone were measured predose (MPA only) and 2, 4, 6, 8, 10, and 12 weeks after a single DMPA 150 mg intramuscular injection. The primary outcome measure, MPA concentration (<0.1 ng/mL) at week 12, was assessed using exact 95% Clopper-Pearson confidence intervals. MPA PK parameters were calculated using noncompartmental analysis.
RESULTS
Among 42 PK-evaluable women from 5 African countries, median age was 32 years and median CD4 was 414 cells/mm3. Five women (11.9%; 95% CI, 4.0-25.6%) had MPA <0.1 ng/mL at week 12; of these, one had MPA <0.1 ng/mL at week 10. The median clearance of MPA was 19 681 L/week compared with 12 118 L/week for historical controls. There were no adverse events related to DMPA, and progesterone concentrations were <1 ng/mL for all women for the study duration.
CONCLUSIONS
DMPA, when given with rifampicin and efavirenz, was safe. MPA clearance was higher than in women with HIV not on ART, leading to subtherapeutic concentrations of MPA in 12% of women, suggesting that more frequent dosing might be needed.
CLINICAL TRIALS REGISTRATION
NCT02412436.
Topics: Adult; Africa; Contraceptive Agents, Female; Delayed-Action Preparations; Female; HIV; HIV Infections; Humans; Medroxyprogesterone Acetate; Pregnancy; Reference Standards; Tuberculosis
PubMed: 31504342
DOI: 10.1093/cid/ciz863