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BMJ Sexual & Reproductive Health Jan 2024We sought to determine whether there is evidence to recommend progesterone for individuals not wishing to complete a medication abortion after taking mifepristone.
BACKGROUND
We sought to determine whether there is evidence to recommend progesterone for individuals not wishing to complete a medication abortion after taking mifepristone.
METHODS
We undertook an updated systematic review including a primary search for studies in which individuals received progesterone to reverse the effects of mifepristone, and a secondary search for studies in which individuals received mifepristone alone. We searched PubMed, Embase, Cochrane, CINAHL and grey literature up to December 2022. We used the Joanna Briggs Institute critical appraisal tools for risk of bias assessment. We compared ongoing pregnancy rates among individuals treated with progesterone to those managed expectantly.
RESULTS
We did not find new studies in our secondary search. For the main search, we included three case series and one randomised controlled trial. Data were available for 561 individuals who received progesterone after mifepristone, of whom 271 (48%) had ongoing pregnancies. The quality of the evidence in the case series was low due to methodological and ethical issues. Enrollment in the randomised trial stopped early due to bleeding events in both arms. The ongoing pregnancy rate for individuals ≤7 weeks who received progesterone was 42% (95% CI 37-48) compared with 22% (95% CI 11-39) for mifepristone alone. At 7-8 weeks, the ongoing pregnancy rate was 62% (95% CI 52-71) in the progesterone group and 50% (95% CI 15- 85) in the mifepristone alone group.
CONCLUSION
Based mostly on poor-quality data, it appears the ongoing pregnancy rate in individuals treated with progesterone after mifepristone is not significantly higher compared to that of individuals receiving mifepristone alone.
Topics: Pregnancy; Female; Humans; Progesterone; Mifepristone; Abortion, Induced; Pregnancy Rate
PubMed: 37863512
DOI: 10.1136/bmjsrh-2023-201875 -
Clinical Radiology Aug 2023To conduct a systematic review and meta-analysis to evaluate the whether high mammographic density (MD) is differentially associated with all subtypes of breast cancer. (Meta-Analysis)
Meta-Analysis
AIM
To conduct a systematic review and meta-analysis to evaluate the whether high mammographic density (MD) is differentially associated with all subtypes of breast cancer.
MATERIALS AND METHODS
The PubMed, Cochrane Library, and Embase databases were searched systematically in October 2022 to include all studies that investigated the association between MD and breast cancer subtype. Aggregate data of 17,193 breast cancer cases from 23 studies were selected, including five cohort/case-control and 18 case-only studies. The relative risk (RR) of MD were combined using random/fixed effects models for case-control studies, and for case-only studies, relative risk ratios (RRRs) were a combination of luminal A, luminal B, and HER2-positive versus triple-negative tumours.
RESULTS
Women in the highest density category in case-control/cohort studies had a 2.24-fold (95% confidence interval [CI] 1.53, 3.28), 1.81-fold (95% CI 1.15, 2.85), 1.44-fold (95% CI 1.14, 1.81), and 1.59-fold (95% CI 0.89, 2.85) higher risk of triple-negative, HER-2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B breast cancer compared to women in the lowest density category. RRRs for breast tumours being luminal A, luminal B, and HER-2 positive versus triple-negative in case-only studies were 1.62 (95% CI 1.14, 2.31), 1.81 (95% CI 1.22, 2.71) and 2.58 (95% CI 1.63, 4.08), respectively, for BIRADS 4 versus BIRADS 1.
CONCLUSION
The evidence indicates MD is a potent risk factor for the majority of breast cancer subtypes to different degrees. Increased MD is more strongly linked to HER-2-positive cancers compared to other breast cancer subtypes. The application of MD as a subtype-specific risk marker may facilitate the creation of personalised risk prediction models and screening procedures.
Topics: Female; Humans; Breast Neoplasms; Breast Density; Receptor, ErbB-2; Case-Control Studies; Risk Factors; Receptors, Progesterone
PubMed: 37230842
DOI: 10.1016/j.crad.2023.04.008 -
Contraception May 2024To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs). (Review)
Review
OBJECTIVE
To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs).
DESIGN
Systematic review METHODS: We searched seven databases for peer-reviewed publications from January 1, 2015, through December 31, 2023, including studies of women using ARVs and HCs concurrently with outcomes including therapeutic effectiveness or toxicity, pharmacokinetics (PK), or pharmacodynamics. We summarized findings and used checklists to assess evidence quality.
RESULTS
We included 49 articles, with clinical, ARV or HC PK outcomes reported by 39, 25, and 30 articles, respectively, with some articles reporting outcomes in two or more categories. Fifteen of 18 articles assessing DDIs between efavirenz and progestin implants, emergency contraception, or combined hormonal intravaginal rings found higher pregnancy rates, luteal progesterone levels suggesting ovulation, or reduced progestin PK values. Five studies documented that CYP2B6 single nucleotide polymorphisms exacerbated this DDI. One cohort detected doubled bone density loss with concomitant depot medroxyprogesterone acetate (DMPA) and tenofovir disoproxil fumarate (TDF)-containing ART use versus TDF alone. No other studies described DDIs impacting clinical outcomes. Few adverse events were attributed to ARV-HC use with none exceeding Grade 2. Evidence quality was generally moderate, with dis-similar treatment and control groups, identifying and controlling for confounding, and minimizing attrition bias in the study design being the most frequent limitations.
CONCLUSION
Most ARVs and HCs may be used safely and effectively together. TDF-DMPA DDIs warrant longer-term study on bone health and consideration of alternate combinations. For efavirenz-based ART, client counselling on relative risks, including both potential increase in pregnancy rate with concomitant efavirenz and implant use and lower pregnancy rates compared to other HCs even with concomitant efavirenz use, should continue to allow users comprehensive method choice.
PubMed: 38762199
DOI: 10.1016/j.contraception.2024.110490 -
Archives of Gynecology and Obstetrics Aug 2023To investigate the optimal route of progesterone administration for luteal phase support in a frozen embryo transfer. (Review)
Review
OBJECTIVE
To investigate the optimal route of progesterone administration for luteal phase support in a frozen embryo transfer.
DESIGN
Systematic review.
PATIENTS
Women undergoing frozen embryo transfer (FET).
INTERVENTIONS
We conducted an extensive database search of Medline (PubMed), Embase, Web of Science, and Cochrane Trials Register using relevant keywords and their combinations to find randomized controlled trials (RCTs) comparing the routes (i.e., oral, vaginal, intramuscular) of progesterone administration for luteal phase support (LPS) in artificial FET.
MAIN OUTCOME MEASURES
Clinical pregnancy, live birth, miscarriage.
RESULTS
Four RCTs with 3245 participants undergoing artificial endometrial preparation (EP) cycles during FET were found to be eligible. Four trials compared vaginal progesterone with intramuscular progesterone and two trials compared vaginal progesterone with oral progesterone. One study favored of vaginal versus oral progesterone for clinical pregnancy rates (RR 0.45, 95% CI 0.22-0.92) and other study favored intramuscular versus vaginal progesterone for clinical pregnancy rates (RR 1.46, 95% CI 1.21-1.76) and live birth rates (RR 1.62, 95% CI 1.28-2.05). Tabulation of overall evidence strength assessment showed low-quality evidence on the basis that for each outcome-comparison pair, there were deficiencies in either directness of outcome measurement or study quality.
CONCLUSION
There was little consensus and evidence was heterogeneous on the optimal route of administration of progesterone for LPS during FET in artificial EP cycles. This warrants more trials, indirect comparisons, and network meta-analyses.
PROPERO NO
CRD42021251017.
Topics: Pregnancy; Female; Humans; Progesterone; Luteal Phase; Lipopolysaccharides; Embryo Transfer; Pregnancy Rate
PubMed: 35943567
DOI: 10.1007/s00404-022-06674-2 -
Archives of Gynecology and Obstetrics Apr 2024Short-acting progestin-only injectables containing depot medroxyprogesterone acetate (DMPA) are a safe method of contraception. Although DMPA has been available for... (Review)
Review
PURPOSE
Short-acting progestin-only injectables containing depot medroxyprogesterone acetate (DMPA) are a safe method of contraception. Although DMPA has been available for several decades, there is little data on its influence on the risk of breast cancer. Hence, the aim of this paper was to provide an overview of the existing studies and create clarity regarding a possible association with breast cancer.
METHODS
Literature searches were executed in MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and ICTRP. Search terms were related to DMPA and breast cancer. After elimination of duplicates, 3'850 studies were identified and assessed according to inclusion and exclusion criteria. Finally, ten studies were selected and included in this review.
RESULTS
All the selected papers were case-control-studies, except for one pooled analysis and one study comparing observed and expected number of cancer cases. Most of the included studies found no overall elevated breast cancer incidence in DMPA users, only one study found a slightly increased risk and two studies concluded with a significant increase for the overall breast cancer risk.
CONCLUSION
There is little evidence that DMPA may increase the overall risk for breast cancer. However, the incidence of breast cancer is possibly increased in current and more recent users, especially in women younger than 35 years. Long-term use did not result in any risk increase. Nevertheless, further studies will be necessary to confirm these findings and weigh up the individual risks and benefits of this contraceptive method.
Topics: Female; Humans; Medroxyprogesterone Acetate; Delayed-Action Preparations; Breast Neoplasms; Contraceptive Agents, Female; Progestins
PubMed: 37966517
DOI: 10.1007/s00404-023-07265-5 -
European Journal of Obstetrics,... May 2024Estrogen and progesterone play key roles in the maintenance of pregnancy, and their function is mediated via estrogen receptor 1 (ESR1)/estrogen receptor 2 (ESR2) and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Estrogen and progesterone play key roles in the maintenance of pregnancy, and their function is mediated via estrogen receptor 1 (ESR1)/estrogen receptor 2 (ESR2) and progesterone receptor (PGR), respectively. It has been suggested the genetic variations in ESR1, ESR2, and PGR may contribute to recurrent pregnancy loss (RPL); however, the available evidence remains controversial. This meta-analysis aimed to explore the relation of various polymorphisms in ESR1, ESR2, and PGR genes to the risk of RPL.
METHODS
A systematic literature search was conducted using PubMed and Scopus up to August 2023 to obtain relevant studies. The odds ratios (ORs) with 95% confidence intervals (95% CIs) were computed and pooled with the use of random-effects models to test the associations.
RESULTS
A total of 31 studies with 12 different polymorphisms, including 5 polymorphisms for ESR1, 3 polymorphisms for ESR2, and 4 polymorphisms for PGR, were analyzed in this meta-analysis. Overall, no significant relationship was found between various polymorphisms of ESR1 and ESR2 with RPL in any of the genetic analysis models. PGR rs590688 (C > G) polymorphism was significantly related to the elevated risk of RPL under the dominant (OR = 1.67; 95 %CI: 1.15-2.44), allelic (OR = 1.55; 95 %CI: 1.13-2.12), and GC vs. CC (OR = 1.55; 95 %CI: 1.07-2.23) models. No significant association was identified for other variants of PGR gene.
CONCLUSION
Unlike estrogen receptors, variations in PGR rs590688 (C > G) may be linked to the increased risk of RPL. More studies are required to confirm this finding.
Topics: Female; Humans; Pregnancy; Abortion, Habitual; Estrogen Receptor alpha; Estrogen Receptor beta; Genetic Predisposition to Disease; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptors, Estrogen; Receptors, Progesterone
PubMed: 38402782
DOI: 10.1016/j.ejogrb.2024.01.008 -
Biomedicines May 2024Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is... (Review)
Review
Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is characterized by deviations from the typical microscopic appearance of endometriosis, including cytologic and architectural atypia. AE has been recognized as a potential precursor to endometriosis-associated ovarian cancers (EAOC), particularly endometrioid and clear cell subtypes. AE presents challenges in diagnosis due to its diverse clinical and pathological features, often requiring careful histological evaluation for accurate identification. Architectural AE, defined by localized proliferation of crowded glands with atypical epithelium resembling endometrial neoplasia, and cytologic AE, characterized by nuclear atypia within the epithelial lining of endometriotic cysts, are key subtypes. Immunohistochemical and molecular studies have revealed aberrant expression of markers such as Ki67, COX-2, BAF250a, p53, estrogen receptor, progesterone receptor, and IMP-3. Long-term follow-up studies suggest relatively low recurrence and malignant transformation rates among patients with AE, but uncertainties persist regarding its exact malignancy potential and optimal management strategies. Integration of artificial intelligence and shared molecular aberrations between AE and EAOC may enhance diagnostic accuracy. Continuous interdisciplinary collaboration and ongoing research efforts are crucial for a deeper understanding of the relationship between endometriosis and carcinogenesis, ultimately improving patient care and surveillance.
PubMed: 38927416
DOI: 10.3390/biomedicines12061209 -
BMC Pregnancy and Childbirth Feb 2024About 25% of pregnant women experience bleeding in the early stage, and half of them eventually progress to pregnancy loss. Progesterone serves as a useful biomarker to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
About 25% of pregnant women experience bleeding in the early stage, and half of them eventually progress to pregnancy loss. Progesterone serves as a useful biomarker to predict miscarriage in threatened miscarriage, yet its performance is still debated.
AIM
To evaluate the performance of single serum progesterone predicting miscarriage in early pregnant patients with threatened miscarriage.
METHOD
The online database was searched to yield the literature using the terms of 'Abortion', 'Miscarriage', and 'serum Progesterone', including PubMed, Scopus, Embase, Cochrane library, and China national knowledge infrastructure. Receiver operating characteristic (ROC) curve, likelihood ratio (LLR) and diagnostic odds ratio (DOR) and 95% confidence interval (CI) were computed. Publication bias was assessed by the deeks funnel plot asymmetry test. Subgroup analyses were conducted according to the progesterone level (< 12 ng/mL), recruited location and region, progesterone measurement method, exogenous progesterone supplement and follow up.
RESULTS
In total, 12 studies were eligible to be included in this study, with sample sizes ranging from 76 to 1087. The included patients' gestational age was between 4 and 12 weeks. No significant publication bias was detected from all included studies. The threshold of progesterone reported ranged from 8 to 30 ng/ml. The synthesized area under the ROC curve (0.85, 95% CI 0.81 to 0.88), positive LLR (6.2, 4.0 to 9.7) and DOR (18, 12 to 27) of single progesterone measurement distinguishing miscarriage were relatively good in early pregnant patients with threatened miscarriage. When the threshold of < 12 ng/mL was adapted, the progesterone provided a higher area under the ROC curve (0.90 vs. 0.78), positive LLR (8.3 vs. 3.8) and DOR (22 vs.12) than its counterpart (12 to 30 ng/mL).
CONCLUSION
Single progesterone measurement can act as a biomarker of miscarriage in early pregnant patients with threatened miscarriage, and it has a better performance when the concentration is <12 ng/mL.
TRIAL REGISTRATION
PROSPERO (CRD42021255382).
Topics: Pregnancy; Humans; Female; Infant, Newborn; Infant; Progesterone; Abortion, Spontaneous; Abortion, Threatened; Pregnant Women; Biomarkers
PubMed: 38350926
DOI: 10.1186/s12884-024-06303-7 -
Current Environmental Health Reports Dec 2023Organochlorine pesticides (OCP) have been proposed as potential mammary carcinogens since they interact with steroid signaling pathways. However, the epidemiological... (Meta-Analysis)
Meta-Analysis
Exposure to Organochlorine Pesticides and Female Breast Cancer Risk According to Molecular Receptors Expression: a Systematic Review and Meta-analysis of Epidemiological Evidence.
PURPOSE OF REVIEW
Organochlorine pesticides (OCP) have been proposed as potential mammary carcinogens since they interact with steroid signaling pathways. However, the epidemiological results are not conclusive. Most studies have evaluated breast cancer (BC) as a single entity without considering the different molecular expressions, including estrogen receptor (ER), progesterone receptor (PR), and HER2, that could differ in their association with these contaminants. Hence, we assessed the association between biological concentration of OCP and BC, according to its molecular receptor expression, based on a systematic review and meta-analysis.
RECENT FINDINGS
Of the 141 articles eligible for full-text review, nine met the inclusion criteria. The way in which molecular expression was reported was heterogeneous; therefore, the inclusion of studies in the meta-analysis was limited to eight articles. A negative association was identified for β-hexachlorocyclohexane and trans-nonachlor with ER + tumors and between hexachlorobenzene and ER - tumors. No associations were observed for p,p'-dichlorodiphenyldichloroethylene, cis-nonachlor, and dieldrin, and it was not possible to evaluate the associations between OCP with HER2 expression or triple-negative tumors due to lack of data. The results suggest that some OCP might be associated with BC depending on the expression of ER. However, the evidence is not conclusive due to the scarce data. We identified several methodological aspects to fill the gaps in knowledge and increase the comparability among studies.
Topics: Female; Humans; Breast Neoplasms; Dichlorodiphenyl Dichloroethylene; Hydrocarbons, Chlorinated; Pesticides
PubMed: 37639190
DOI: 10.1007/s40572-023-00408-5 -
BMC Women's Health Jun 2024The sex steroid hormones fluctuate during the menstrual cycle, which affects the strength and postural stability of females and leads to injuries and risk of falls.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The sex steroid hormones fluctuate during the menstrual cycle, which affects the strength and postural stability of females and leads to injuries and risk of falls. These hormones may be modulated by exercise to impact the overall health of females.
OBJECTIVE
To determine the effects of exercise on sex steroid hormones in eumenorrheic females.
METHODS
This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines in Lahore, Pakistan. The full-length articles were searched using these databases/search engines (PubMed, Web of Science and Google Scholar, Sci-Hub). Randomized controlled trials along with single group experimental studies were also included. All types of exercises were compared with no exercise in the control group. The Cochrane Risk of Bias assessment tool assessed and screened the articles. The data were then analyzed. The primary outcomes were the levels of estrogen, progesterone and testosterone.
RESULTS
Eleven studies were included (5 randomized controlled trials and 6 quasi-experimental studies). The effects of exercise on free estradiol concentration and serum progesterone level were not significant [p = 0.37 (SMD = 0.33, 95% CI = 0.14 to 0.74, I = 0%) and p = 0.84 (S.D= -0.65, C.I= -6.92 to 5.62, I = 94%)] respectively, whereas, the effects on testosterone levels were significant [p value < 0.00001 (M.D = 0.89, 95% C.I= -2.16 to 3.95, I = 94%)].
CONCLUSION
A blinded randomized controlled trial should be conducted in which a structured approach should be followed by women along with warm-ups, cool down and rest intervals.
TRIAL REGISTRATION NUMBER
The systematic review was registered prospectively on PROSPERO with registration number CRD42023473767.
Topics: Humans; Female; Progesterone; Exercise; Testosterone; Estrogens; Gonadal Steroid Hormones; Randomized Controlled Trials as Topic; Estradiol
PubMed: 38890710
DOI: 10.1186/s12905-024-03203-y