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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 -
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 Complementary Medicine and Therapies Feb 2023Guizhi Fuling Capsule (GZFL), a classic traditional Chinese medicine prescription, is often recommended for the treatment of uterine fibroids (UFs). However, the... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of Chinese herbal medicine Guizhi Fuling capsule combined with low dose mifepristone in the treatment of uterine fibroids: a systematic review and meta-analysis of 28 randomized controlled trials.
OBJECTIVE
Guizhi Fuling Capsule (GZFL), a classic traditional Chinese medicine prescription, is often recommended for the treatment of uterine fibroids (UFs). However, the efficacy and safety of GZFL in combination with low-dose mifepristone (MFP) remains controversial.
MATERIALS AND METHODS
We searched eight literature databases and two clinical trial registries for randomized controlled trials (RCTs) of the efficacy and safety of GZFL combined with low-dose MFP in the treatment of UFs from database inception to April 24, 2022. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. GRADE pro3.6.1 software was used for the assessment of evidence quality.
RESULTS
Twenty-eight RCTs were included in this study, including a total of 2813 patients. The meta-analysis showed that compared with low-dose MFP alone, GZFL combined with low-dose MFP significantly reduced follicle stimulating hormone (p < 0.001), estradiol (p < 0.001), progesterone (p < 0.001), luteinizing hormone (p < 0.001), uterine fibroids volume (p < 0.001), uterine volume (p < 0.001), menstrual flow (p < 0.001) and increased clinical efficiency rate (p < 0.001). Meanwhile, GZFL combined with low-dose MFP did not significantly increase the incidence of adverse drug reactions compared with low-dose MFP alone (p = 0.16). The quality of the evidence for the outcomes ranged from "very low" to "moderate."
CONCLUSION
This study suggests that GZFL combined with low-dose MFP is more effective and safe in the treatment of UFs, and it is a potential treatment for UFs. However, due to the poor quality of the included RCTs formulations, we recommend a rigorous, high-quality, large-sample trial to confirm our findings.
Topics: Female; Humans; Mifepristone; Drugs, Chinese Herbal; Wolfiporia; Randomized Controlled Trials as Topic; Leiomyoma
PubMed: 36803997
DOI: 10.1186/s12906-023-03842-y -
Fertility and Sterility Jun 2023Over the last decade, frozen embryo transfer (FET) has been increasingly used in contemporary fertility units. Despite the rapid increase in FET, there is still... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Over the last decade, frozen embryo transfer (FET) has been increasingly used in contemporary fertility units. Despite the rapid increase in FET, there is still insufficient evidence to recommend an optimized protocol for endometrial preparation especially in patients with lower progesterone (P4) levels. Previous studies have concluded that P4 levels <10 ng/mL are associated with poorer pregnancy outcomes than those reported with high levels of circulating P4.
OBJECTIVE
To identify whether rescue P4 dosing in patients with low P4 can salvage adverse outcomes associated with low P4 levels, resulting in outcomes comparable to patients with adequate progesterone.
DATA SOURCES
The study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analyses guidelines and prospectively registered under the PROSPERO database (CRD42022357125). Six databases (Embase, MEDLINE, APA PsycInfo, Global Health, HMIC Health Management Information Consortium, and Google Scholar) and 2 additional sources were searched from inception to August 29, 2022.
STUDY SELECTION AND SYNTHESIS
Prospective and retrospective cohort studies, reporting the association between rescue progesterone and one or more pregnancy outcomes, were included. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS), while the quality of evidence by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Summative and subgroup data as well as heterogeneity were generated by the Cochrane platform RevMan (V. 5.4).
MAIN OUTCOME MEASURE(S)
To compare ongoing pregnancy rate as primary outcome and clinical pregnancy rate, miscarriage rate, and live birth rate as secondary outcomes between patients with low (<10 ng/mL) receiving rescue progesterone vs. those with adequate levels of P4 (≥10 ng/mL).
RESULT(S)
Overall, 7 observational studies were included in the analysis, with a total of 5927 patients of median age 34 (interquartile range [IQR]: 31.55, 37.13). Overall, patient group comparison, namely those with low P4 that received a rescue dose and those with adequate P4 levels, did not yield significant differences for either the primary or secondary outcomes. For ongoing clinical pregnancy, patients with low P4 receiving the rescue dose vs. those with adequate P4 levels was odds ratio (OR) 0.98 (95% CI: 0.78, 1.24; P = .86, I: 41%), whereas for miscarriage events, OR was 0.98 (95% CI: 0.81, 1.17; P = .80, I: 0). Equally, for clinical pregnancy, OR was 0.91 (95% CI: 0.78, 1.06; P = .24; I: 33%), and for live birth, OR was 0.92 (95% CI: 0.77, 1.09; P = .33; I: 43%). Subgroup analysis on the basis or rescue administration route successfully explained summative heterogeneity.
CONCLUSION(S)
Rescue P4 dosing in patients with low P4 results in ongoing pregnancy rate, clinical pregnancy and live birth rates were comparable to those of patients with adequate P4 levels. However, robust randomized controlled trials assessing rescue treatment in women with low P4 are needed to confirm these findings. Rescue P4 in patients with low circulating P4 around embryo transfer day may result in reproductive outcomes comparable to those with adequate P4 levels.
STUDY REGISTRATION
CRD42022357125 (PROSPERO).
Topics: Pregnancy; Humans; Female; Adult; Progesterone; Abortion, Spontaneous; Prospective Studies; Retrospective Studies; Embryo Transfer; Pregnancy Rate; Live Birth
PubMed: 36781098
DOI: 10.1016/j.fertnstert.2023.02.007 -
Cancers Feb 2023Meningiomas are, in most cases, low grade intracranial tumors. However, relapses are frequent. To date, only a few prognostic markers are described in the literature.... (Review)
Review
Meningiomas are, in most cases, low grade intracranial tumors. However, relapses are frequent. To date, only a few prognostic markers are described in the literature. Several studies have discussed the expression of progesterone, estrogen, androgen, and somatostatin receptors. The utility of analyzing these expressions for prognostic, theragnostic, and therapeutic purposes remains unclear. The aim of this study was to report the expression of these receptors, based on immunohistochemistry. Cochrane Collaboration guidelines and PRISMA statements were followed. We did an online search in PubMed using the MeSH database. References were selected if the investigations occurred from 1990 to 2022. 61 references were included (34 descriptive observational studies, 26 analytical observational studies, and one case report). In this review, we describe the expression of these receptors in function of age, sex, hormonal context, localization, histological subtype, grade, and recurrence.
PubMed: 36765937
DOI: 10.3390/cancers15030980 -
Frontiers in Neuroendocrinology Apr 2023In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter...
In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter systems. Several parallels between progesterone and older generation progestin actions emerged, suggesting actions via progesterone receptors. However, existing results suggest a general lack of knowledge regarding the effects of currently used progestins in hormonal contraception regarding these cellular and molecular brain parameters. Human neuroimaging studies were reviewed with a focus on randomized placebo-controlled trials and cross-sectional studies controlling for progestin type. The prefrontal cortex, amygdala, salience network and hippocampus were identified as regions of interest for future preclinical studies. This review proposes a series of experiments to elucidate the cellular and molecular actions of contraceptive progestins in these areas and link these actions to behavioral markers of emotional and cognitive functioning. Emotional effects of contraceptive progestins appear to be related to 1) alterations in the serotonergic system, 2) direct/indirect modulations of inhibitory GABA-ergic signalling via effects on the allopregnanolone content of the brain, which differ between androgenic and anti-androgenic progestins. Cognitive effects of combined oral contraceptives appear to depend on the ethinylestradiol dose.
Topics: Animals; Humans; Progestins; Progesterone; Contraceptive Agents; Cross-Sectional Studies; Progesterone Congeners; Brain
PubMed: 36758768
DOI: 10.1016/j.yfrne.2023.101060 -
Journal of Gynecologic Oncology Mar 2023To conduct a systematic review and meta-analysis of studies evaluating the oncological and fertility outcomes of early-stage endometrial cancer (EC) treated with the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a systematic review and meta-analysis of studies evaluating the oncological and fertility outcomes of early-stage endometrial cancer (EC) treated with the levonorgestrel-releasing intrauterine system (LIUS)-based regimens.
METHODS
The Meta-analyses Of Observational Studies in Epidemiology statement for meta-analyses was followed. Searches were conducted on MEDLINE, Embase, PubMed, Preprints, and the Cochrane Central Register of Controlled Trials from January 1990 to August 4, 2022. The Joanna Briggs Institute Critical Appraisal Checklist was used for quality assessment. The primary endpoint was the complete response (CR) rate and the secondary endpoints were relapse, pregnancy, and live birth rate.
RESULTS
A total of 25 studies (821 women) were included. The CR rate of LIUS-based regimens was 63.4% (95% confidence interval [CI]=52.3%-73.2%), with 29.6% (95% CI=23.3%-36.8%) of cases experiencing recurrence during follow-up. In sensitivity analyses, patients younger than 45 years of age with a body mass index <30 kg/m² who were treated with LIUS-based regimens achieved a high CR rate of 84.6% (95% CI=80.3%-88.1%) over a median follow-up of more than 24 months. Overall pregnancy and live birth rates were 37.9% (95% CI=24.1%-53.9%) and 39.3% (95% CI=24.0%-57.0%), respectively. No statistical differences were apparent in CR or relapse rates among the LIUS+GnRH agonist, LIUS+oral progesterone, or hysteroscopic resection followed by LIUS subgroups.
CONCLUSION
LIUS-based therapies are viable for the conservative management of early-stage endometrioid EC on CR and fertility outcome.
TRIAL REGISTRATION
PROSPERO Identifier: CRD42022352890.
Topics: Pregnancy; Humans; Female; Child, Preschool; Levonorgestrel; Intrauterine Devices, Medicated; Neoplasm Recurrence, Local; Endometrium; Carcinoma, Endometrioid; Endometrial Neoplasms
PubMed: 36731895
DOI: 10.3802/jgo.2023.34.e36 -
Endocrinology Feb 2023The objective of this systematic review was to investigate the association between polymorphisms in the progesterone receptor gene (PGR) and breast cancer risk. A search...
The objective of this systematic review was to investigate the association between polymorphisms in the progesterone receptor gene (PGR) and breast cancer risk. A search of PubMed, Scopus, and Web of Science databases was performed in November 2021. Study characteristics, minor allele frequencies, genotype frequencies, and odds ratios were extracted. Forty studies met the eligibility criteria and included 75 032 cases and 89 425 controls. Of the 84 PGR polymorphisms reported, 7 variants were associated with breast cancer risk in at least 1 study. These polymorphisms included an Alu insertion (intron 7) and rs1042838 (Val660Leu), also known as PROGINS. Other variants found to be associated with breast cancer risk included rs3740753 (Ser344Thr), rs10895068 (+331G/A), rs590688 (intron 2), rs1824128 (intron 3), and rs10895054 (intron 6). Increased risk of breast cancer was associated with rs1042838 (Val660Leu) in 2 studies, rs1824128 (intron 3) in 1 study, and rs10895054 (intron 6) in 1 study. The variant rs3740753 (Ser344Thr) was associated with decreased risk of breast cancer in 1 study. Mixed results were reported for rs590688 (intron 2), rs10895068 (+331G/A), and the Alu insertion. In a pooled analysis, the Alu insertion, rs1042838 (Val660Leu), rs3740753 (Ser344Thr), and rs10895068 (+331G/A) were not associated with breast cancer risk. Factors reported to contribute to differences in breast cancer risk associated with PGR polymorphisms included age, ethnicity, obesity, and postmenopausal hormone therapy use. PGR polymorphisms may have a small contribution to breast cancer risk in certain populations, but this is not conclusive with studies finding no association in larger, mixed populations.
Topics: Humans; Female; Breast Neoplasms; Receptors, Progesterone; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Genotype
PubMed: 36702635
DOI: 10.1210/endocr/bqad020 -
Journal of Assisted Reproduction and... Mar 2023
PubMed: 36652118
DOI: 10.1007/s10815-023-02718-x -
Transgender Health Nov 2022Gender-affirming hormone therapy is critical to the management of transgender persons. Cyproterone acetate (CPA) is a synthetic, progesterone-like compound commonly used... (Review)
Review
BACKGROUND
Gender-affirming hormone therapy is critical to the management of transgender persons. Cyproterone acetate (CPA) is a synthetic, progesterone-like compound commonly used in high doses as gender-affirming progestogen therapy in transgender women. An association between high-dose CPA and the development and growth of intracranial meningioma, including case reports in transgender women, has been described. This systematic review summarizes these cases at the patient level and discusses their management.
METHODS
This systematic review was registered with PROSPERO (CRD42020191965). A detailed search of the PubMed, EMBASE, and Web of Science electronic bibliographic databases was performed (inception-December 20, 2020). Two review authors independently completed screening, data extraction, and risk of bias assessment in duplicate.
RESULTS
Nine records were included describing (=12) individual case reports and (=35) intracranial meningiomas. The median age at presentation was 48 years (interquartile range [IQR], 43-55 years), most frequent daily CPA doses were 50 mg/day (=5) and 100 mg/day (=5), and the median duration of CPA use was 9.5 years (IQR, 6.5-17.5 years). Multiple meningiomas were common (=7). For most cases (=10), surgical resection was the initial preferred management strategy, but two were successfully managed by CPA cessation.
CONCLUSIONS
Transgender women receiving high doses of CPA may be at increased risk of intracranial meningioma development and/or growth, although this remains a rare disease. For presumed CPA-associated meningioma, drug cessation appears to be an appropriate management strategy when surgery is not imminently required to manage raised intracranial pressure or prevent neurological deterioration. Given the importance of gender-affirming hormone therapy to transgender persons, a suitable alternative hormone regimen should be offered, although the use of CPA in both high doses and for prolonged periods of time is now in decline.
PubMed: 36644118
DOI: 10.1089/trgh.2021.0025