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Frontiers in Endocrinology 2022Progesterone plays a key role in implantation. Several studies reported that lower luteal progesterone levels might be related to decreased chances of pregnancy. This... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Progesterone plays a key role in implantation. Several studies reported that lower luteal progesterone levels might be related to decreased chances of pregnancy. This systematic review was conducted using appropriate key words, on MEDLINE, EMBASE, and the Cochrane Library, from 1990 up to March 2021 to assess if luteal serum progesterone levels are associated with ongoing pregnancy (OP) and live birth (LB) rates (primary outcomes) and miscarriage rate (secondary outcome), according to the number of corpora lutea (CLs). Overall 2,632 non-duplicate records were identified, of which 32 relevant studies were available for quantitative analysis. In artificial cycles with no CL, OP and LB rates were significantly decreased when the luteal progesterone level falls below a certain threshold (risk ratio [RR] 0.72; 95% confidence interval [CI] 0.62-0.84 and 0.73; 95% CI 0.59-0.90, respectively), while the miscarriage rate was increased (RR 1.48; 95% CI 1.17-1.86). In stimulated cycles with several CLs, the mean luteal progesterone level in the no OP and no LB groups was significantly lower than in the OP and LB groups [difference in means 68.8 (95% CI 45.6-92.0) and 272.4 (95% CI 10.8-533.9), ng/ml, respectively]. Monitoring luteal serum progesterone levels could help in individualizing progesterone administration to enhance OP and LB rates, especially in cycles without corpus luteum.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=139019, identifier 139019.
Topics: Abortion, Spontaneous; Birth Rate; Corpus Luteum; Female; Humans; Luteal Phase; Pregnancy; Pregnancy Rate; Progesterone
PubMed: 35757393
DOI: 10.3389/fendo.2022.892753 -
Heliyon Jun 2023To systematically review and summarize the existing evidence related to the influence of the menstrual cycle (MC) and hormonal contraceptive (HC) use on O in physically...
OBJECTIVE
To systematically review and summarize the existing evidence related to the influence of the menstrual cycle (MC) and hormonal contraceptive (HC) use on O in physically active women.
METHODS
This systematic review and meta-analysis conforms to the PRISMA statement guidelines. Four (sub-)meta-analyses were performed. Two focused on longitudinal studies examining the same women several times to compare the O during the different menstrual phases or oral contraceptive (OC) use and withdrawal. Two meta-analyses examined if there is a difference in O between OC users and normally menstruating women by analyzing cross-sectional studies assigning physically active women to one of these two groups as well as intervention-based studies (cross-over studies, randomized controlled trials considering only the data of the intervention group) comparing women intra-individually with and without OCs.
RESULTS
Nine of the included studies (107 women) evaluated the influence of the MC, five studies (69 women) the impact of OCs on O, and six studies investigated both topics (88 women). A mean difference of O -0.03 ml/kg/min (95%CI -1.06 to 1.01) between the early follicular and luteal menstrual phase was observed. Between the active and inactive phases of OCs, a mean difference of -0.11 ml/kg/min (95%CI -2.32 to 2.10) was found. The inter-individual comparison of naturally menstruating women and OC users showed a mean difference in O of 0.23 ml/kg/min (95% CI -2.33 to 2.79) in favor of OC use. The intra-individual comparison of the same women showed a mean decrease in O of -0.84 ml/kg/min (95% CI -2.38 to 0.70) after a new start with OCs.
CONCLUSIONS
Our meta-analyses showed no effects of the MC or the OCs on O. More high-quality studies are needed determining the MC phases more precisely, including OCs with the current standard formulations and comparing the influence of different progestins.
PubMed: 37484400
DOI: 10.1016/j.heliyon.2023.e17049 -
Annals of Palliative Medicine Oct 2021This study aimed to explore the clinical efficacy of dydrogesterone in treating recurrent spontaneous abortion (RSA), analyze the influence of dydrogesterone on cellular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aimed to explore the clinical efficacy of dydrogesterone in treating recurrent spontaneous abortion (RSA), analyze the influence of dydrogesterone on cellular immune factors, and provide evidence for clinical medication.
METHODS
We used the China National Knowledge Infrastructure (CNKI) platform, Wanfang Data resource, PubMed, Web of Science, and Embase database to conduct a literature search to screen clinical studies published between 2005 and 2021 concerning dydrogesterone treatment for RSA. Stata 16.0 was used for meta-analysis and sensitivity analysis, and Begg's funnel chart was used to test publication bias.
RESULTS
Only 13 studies, which included a total of 2,454 RSA patients, met the study inclusion criteria. The experimental group was treated with dydrogesterone, and the control group was treated with progesterone, human chorionic gonadotropin (hCG), placebo, or active immunization. Meta-analysis showed that the pregnancy success rate of the experimental group was higher than the control group, and the adverse reaction rate was lower than the control group. In addition, subgroup analysis also revealed that the experimental group had a higher pregnancy success rate than the control group and a lower adverse reaction rate. Levels of progesterone and hCG in the experimental group were dramatically higher than the control group after treatment. The experimental group also had higher levels of interleukin 4 (IL-4) and interleukin 10 (IL-10) than the control group, while levels of interferon-gamma (IFN-γ) were lower.
DISCUSSION
Dydrogesterone, a safe and effective synthetic progesterone drug, had a significant clinical effect on RSA and effectively improved hormone levels and related cellular immune factors in RSA patients.
Topics: Abortion, Habitual; China; Dydrogesterone; Female; Humans; Immunologic Factors; Pregnancy; Progesterone
PubMed: 34763460
DOI: 10.21037/apm-21-2605 -
PloS One 2023Prevention of preterm birth (PTB) with progestogens after an episode of threatened preterm labour is still controversial. As different progestogens have distinct... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Prevention of preterm birth (PTB) with progestogens after an episode of threatened preterm labour is still controversial. As different progestogens have distinct molecular structures and biological effects, we conducted a systematic review and pairwise meta-analysis to investigate the individual role played by 17-alpha-hydroxyprogesterone caproate (17-HP), vaginal progesterone (Vaginal P) and oral progesterone (Oral P).
METHODS
The search was performed in MEDLINE, ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials (CENTRAL) up to 31 October 2021. Published RCTs comparing progestogens to placebo or no treatment for maintenance tocolysis were considered. We included women with singleton gestations, excluding quasi-randomized trials, studies on women with preterm premature rupture of membrane, or receiving maintenance tocolysis with other drugs. Primary outcomes were preterm birth (PTB) < 37 weeks' and < 34 weeks'. We assessed risk of bias and evaluated certainty of evidence with the GRADE approach.
RESULTS
Seventeen RCTs including 2152 women with singleton gestations were included. Twelve studies tested vaginal P, five 17-HP, and only 1 oral P. PTB < 34 weeks' did not differ among women receiving vaginal P (RR 1.21, 95%CI 0.91 to 1.61, 1077 participants, moderate certainty of evidence), or oral P (RR 0.89, 95%CI 0.38 to 2.10, 90 participants, low certainty of evidence) as opposed to placebo. Instead, 17-HP significantly reduced the outcome (RR 0.72, 95% CI 0.54 to 0.95, 450 participants, moderate certainty of evidence). PTB < 37 weeks' did not differ among women receiving vaginal P (RR 0.95, 95%CI 0.72 to 1.26, 8 studies, 1231 participants, moderate certainty of evidence) or 17-HP (RR 0.86, 95%CI 0.60 to 1.21, 450 participants, low certainty of evidence) when compared to placebo/no treatment. Instead, oral P significantly reduced the outcome (RR 0.58, 95% CI 0.36 to 0.93, 90 participants, low certainty of evidence).
CONCLUSIONS
With a moderate certainty of evidence, 17-HP prevents PTB < 34 weeks' gestation among women that remained undelivered after an episode of threatened preterm labour. However, data are insufficient to generate recommendations in clinical practice. In the same women, both 17-HP and vaginal P are ineffective in the prevention of PTB < 37 weeks'.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Progestins; Progesterone; Premature Birth; Tocolysis; Obstetric Labor, Premature
PubMed: 36812243
DOI: 10.1371/journal.pone.0277563 -
BMC Women's Health Dec 2022Endometriosis is a complex chronic disease that affects approximately 10% of women of reproductive age worldwide and commonly presents with pelvic pain and infertility. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometriosis is a complex chronic disease that affects approximately 10% of women of reproductive age worldwide and commonly presents with pelvic pain and infertility.
METHOD & OUTCOME MEASURES
A systematic review of the literature was carried out using the databases Pubmed, Scopus, Cochrane and ClinicalTrials.gov in women with a confirmed laparoscopic diagnosis of endometriosis receiving progestins to determine a reduction in pain symptoms and the occurrence of adverse effects.
RESULTS
Eighteen studies were included in the meta-analysis. Progestins improved painful symptoms compared to placebo (SMD = -0.61, 95% CI (-0.77, -0.45), P < 0.00001) with no comparable differences between the type of progestin. After median study durations of 6-12 months, the median discontinuation rate due to adverse effects was 0.3% (range: 0 - 37.1%) with mild adverse effects reported.
CONCLUSION
The meta-analysis revealed that pain improvement significantly increased with the use of progestins with low adverse effects.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021285026.
Topics: Female; Humans; Endometriosis; Laparoscopy; Pelvic Pain; Progestins
PubMed: 36528558
DOI: 10.1186/s12905-022-02122-0 -
Research and Practice in Thrombosis and... May 2021Randomized controlled trials on menopausal hormone therapy in humans have not confirmed the benefit of estrogens on cardiovascular disease found in animal studies....
BACKGROUND
Randomized controlled trials on menopausal hormone therapy in humans have not confirmed the benefit of estrogens on cardiovascular disease found in animal studies. Flawed methodology or publication bias in animal studies may explain the dicrepancy.
OBJECTIVES
The aim of this study was to investigate whether publication of the randomized controlled trials Heart and Estrogen/Progestin Replacement Study and Women's Health Initiative influenced study authors' assessment of research findings (confirmation bias) as well as to investigate publication bias and small-study effects in animal studies of estrogen effects on atherosclerosis.
METHODS
The data source for this study was PubMed from inception to 2018. We selected animal studies with cardiovascular outcomes comparing 17-β-estradiol, its natural metabolites, or conjugated equine estrogen with control. Qualitative data were extracted on authors' conclusions about estrogen effects on cardiovascular disease, as well as quantitative data for atherosclerosis outcomes. Fixed- and random-effects meta-analyses were used. Publication bias/small-study effects were assessed using funnel plots and Egger's regression. Trim-and-fill plots and extrapolation from Egger's regression were used to adjust for publication bias. The main outcomes and measures were the primary study authors' interpretation of their own results, and estrogen effects on cardiovascular disease in general before and after publication of the Women's health Initiative study (2003). The effects of estrogens on atherosclerosis were measured as standardized mean difference between intervention and control.
RESULTS
Of 1925 studies retrieved, 360 were eligible for analyses. Study-specific statements concluded that estrogens were protective against cardiovascular disease in 75% of studies before 2003 and 78% after, but the percentage of general statements about estrogens being cardioprotective changed from 70% to 40%. Meta-analyses showed less atherosclerosis in estrogen-treated animals. Extremely skewed funnel plots and < .01 in Egger's regression suggested publication bias and/or exaggerated effects in small studies, which was more pronounced after 2002. There was substantial heterogeneity of effects ( = 68%-86%) overall and in all subgroups except cynomolgus monkeys ( = 9%), the only animal subgroup without clear bias. Adjusting for publication bias, overall estimates of estrogen effects on atherosclerosis were close to null effect.
CONCLUSIONS
We found substantial evidence of publication bias but not of confirmation bias. Publication bias and flawed small studies may partly explain why findings differ between animal studies and clinical trials on the effect of estrogens on cardiovascular disease.
PubMed: 34013151
DOI: 10.1002/rth2.12507 -
Scientific Reports Jul 2022Hormone replacement therapy (HRT) is widely used to relieve menopausal symptoms; however, it remains unclear whether the use of HRT was associated with gastric cancer.... (Meta-Analysis)
Meta-Analysis
Hormone replacement therapy (HRT) is widely used to relieve menopausal symptoms; however, it remains unclear whether the use of HRT was associated with gastric cancer. We conducted a systematic review and meta-analysis to synthesize available evidence. This study followed the PRISMA guideline to report meta-analysis. PubMed, Embase, and Cochrane library were searched from conception through 23 February 2022. Eligible studies reporting risk of gastric cancer after HRT were screened and accessed by two independent reviewers. Random-effects meta-analysis was used to calculate pooled risk estimate as relative risk (RR, 95% CI). Pre-established review protocol was registered in PROSPERO (CRD42021281260). Among the 1095 articles identified, we included 11 studies with 1,919,089 women in this meta-analysis. The combined risk estimate (RR, 0.72; 95% CI 0.64-0.81; I = 2%) indicated that the use of HRT was associated with a 28% reduction in risk of gastric cancer compared with those who had no HRT exposure. The narrow prediction interval (0.62-0.84) for gastric cancer risk suggested a low between-study variance. In subgroup analysis defined by HRT formulation, there were reduction in risks of gastric cancer after the use of estrogen-only therapy (Pooled RR, 0.63; 95% CI 0.51-0.77, I = 0%) and estrogen-progestin therapy (Pooled RR, 0.70; 95% CI 0.57-0.87; I = 0%), as compared with non-users. In this systematic review and meta-analysis, the use of HRT was associated with a reduced gastric cancer risk regardless of HRT formulation. Further investigations are warranted to confirm underlying mechanisms.
Topics: Estrogen Replacement Therapy; Estrogens; Female; Hormone Replacement Therapy; Humans; Risk; Stomach Neoplasms
PubMed: 35906381
DOI: 10.1038/s41598-022-17345-2 -
Human Reproduction Update Jun 2020Despite intense research, it remains intriguing why hormonal therapies in general and progestins in particular sometimes fail in endometriosis.
BACKGROUND
Despite intense research, it remains intriguing why hormonal therapies in general and progestins in particular sometimes fail in endometriosis.
OBJECTIVE AND RATIONALE
We review here the action mechanisms of progesterone receptor ligands in endometriosis, identify critical differences between the effects of progestins on normal endometrium and endometriosis and envisage pathways to escape drug resistance and improve the therapeutic response of endometriotic lesions to such treatments.
SEARCH METHODS
We performed a systematic Pubmed search covering articles published since 1958 about the use of progestins, estro-progestins and selective progesterone receptor modulators, to treat endometriosis and its related symptoms. Two reviewers screened the titles and abstracts to select articles for full-text assessment.
OUTCOMES
Progesterone receptor signalling leads to down-regulation of estrogen receptors and restrains local estradiol production through interference with aromatase and 17 beta-hydroxysteroid dehydrogenase type 1. Progestins inhibit cell proliferation, inflammation, neovascularisation and neurogenesis in endometriosis. However, progesterone receptor expression is reduced and disrupted in endometriotic lesions, with predominance of the less active isoform (PRA) over the full-length, active isoform (PRB), due to epigenetic abnormalities affecting the PGR gene transcription. Oxidative stress is another mechanism involved in progesterone resistance in endometriosis. Among the molecular targets of progesterone in the normal endometrium that resist progestin action in endometriotic cells are the nuclear transcription factor FOXO1, matrix metalloproteinases, the transmembrane gap junction protein connexin 43 and paracrine regulators of estradiol metabolism. Compared to other phenotypes, deep endometriosis appears to be more resistant to size regression upon medical treatments. Individual genetic characteristics can affect the bioavailability and pharmacodynamics of hormonal drugs used to treat endometriosis and, hence, explain part of the variability in the therapeutic response.
WIDER IMPLICATIONS
Medical treatment of endometriosis needs urgent innovation, which should start by deeper understanding of the disease core features and diverse phenotypes and idiosyncrasies, while moving from pure hormonal treatments to drug combinations or novel molecules capable of restoring the various homeostatic mechanisms disrupted by endometriotic lesions.
Topics: Endometriosis; Endometrium; Female; Fertility Agents, Female; Humans; Ligands; Peritoneal Diseases; Progesterone; Progestins; Receptors, Progesterone; Treatment Outcome; Uterine Diseases
PubMed: 32412587
DOI: 10.1093/humupd/dmaa009 -
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 -
Talanta Jun 2023The hormones human chorionic gonadotropin, progesterone, estrogen and four of its metabolites (estradiol, estrone, estriol, estetrol), as well as relaxin play an... (Review)
Review
The hormones human chorionic gonadotropin, progesterone, estrogen and four of its metabolites (estradiol, estrone, estriol, estetrol), as well as relaxin play an essential role in the development of the fetus during the first trimester. Imbalances in these hormones during the first trimester have been directly linked to miscarriages. However, frequent monitoring of the hormones is limited by the current conventional centralized analytical tools that do not allow a rapid response time. Electrochemical sensing is considered an ideal tool to detect hormones owing to its advantages such as quick response, user-friendliness, low economic costs, and possibility of use in point-of-care settings. Electrochemical detection of pregnancy hormones is an emerging field that has been demonstrated primarily at research level. Thus, it is timely with a comprehensive overview of the characteristics of the reported detection techniques. This is the first extensive review focusing on the advances related to electrochemical detection of hormones linked to the first trimester of pregnancy. Additionally, this review offers insights into the main challenges that must be addressed imminently to ensure progress from research to clinical applications.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, First; Hormones; Estradiol; Estrone; Progesterone; Estrogens; Estriol; Chorionic Gonadotropin
PubMed: 36870154
DOI: 10.1016/j.talanta.2023.124396