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European Review For Medical and... Jun 2023The aim of the study was to systematically review and meta-analyze the available data on changes in the hormonal profile of postmenopausal women treated with hormone... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of the study was to systematically review and meta-analyze the available data on changes in the hormonal profile of postmenopausal women treated with hormone replacement therapy (HRT).
MATERIALS AND METHODS
Full-text articles published up to April 30, 2021, were searched through PUBMED, EMBASE, the Cochrane library and Web of Science (WOS) databases and were screened strictly according to inclusion criteria. Randomized clinical trials and case control studies were enrolled. Studies not reporting steroid serum levels or not providing a control group were excluded from the analysis. Studies enrolling women with genetic defects or severe chronic systemic diseases were excluded. Data are expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Random effect models were used for the meta-analysis.
RESULTS
HRT administration increases estradiol (E2) and reduces follicle stimulating hormone (FSH) serum levels compared with pre-treatment. Their changes are evident when oral and transdermal HRT are administered, while vaginal HRT not. No significant effect on E2 and FSH was found between 6 and 12 months, as well as between 12 and 24 months. No significant effect on E2 and FSH was shown between different regimes. No difference was observed between different HRT regarding their effect on lipid profiles, breast pain and vaginal bleeding, but oral estrogen combined synthetic progestin caused a reduction in sex hormone-binding globulin (SHGB).
CONCLUSIONS
The review suggested oral and transdermal HRT could lead to a rise in E2 serum levels and a decrease in FSH. The types and doses of HRT did not seem to modify the E2 and FSH level. Also, oral estrogen combined synthetic progestin could cause a reduction in SHGB. This might be crucial when choosing the best possible treatment for each patient individually taking into consideration if potential benefits outweigh the risks.
Topics: Female; Humans; Estrogen Replacement Therapy; Postmenopause; Gonadal Steroid Hormones; Hormone Replacement Therapy; Estradiol; Estrogens; Follicle Stimulating Hormone
PubMed: 37318501
DOI: 10.26355/eurrev_202306_32646 -
European Journal of Endocrinology Jul 2023To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and Management of polycystic ovary syndrome (PCOS).
DESIGN
A systematic review and meta-analysis was performed, Prospero CRD42022345640.
METHODS
MEDLINE, EMBASE, All EBM, CINAHL, and PsycINFO was searched on July, 8, 2022, for studies including women with PCOS, comparing 2 different COCPs in randomized controlled trials.
RESULTS
A total of 1660 studies were identified, and 19 randomized controlled trials (RCTs) were included.Fourth-generation COCP resulted in lower body mass index (BMI) (mean difference [MD] 1.17 kg/m2 [95% confidence interval {CI} 0.33; 2.02]) and testosterone (MD 0.60 nmol/L [95% CI 0.13; 1.07]) compared with third-generation agents, but no difference was seen in hirsutism.Ethinyl estradiol (EE)/cyproterone acetate (CPA) was better in reducing hirsutism as well as biochemical hyperandrogenism (testosterone [MD 0.38 nmol/L {95% CI 0.33-0.43}]) and BMI (MD 0.62 kg/m2 [95% CI 0.05-1.20]) compared with conventional COCPs.There was no difference in hirsutism between high and low EE doses. No evidence regarding natural estrogens in COCP was identified.
CONCLUSION
With current evidence, combined regimens containing an antiandrogen (EE/CPA) may be better compared with conventional COCPs in reducing hyperandrogenism, but EE/CPA will not be recommended as a first-line COCP treatment by the pending PCOS guideline update, due to higher venous thrombotic events (VTE) risk in the general population. Later-generation progestins offer theoretical benefits, but better evidence on clinical outcomes is needed in women with PCOS.
TRIAL REGISTRATION
The protocol for the systematic review was registered prospectively in Prospero, CRD42022345640.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hirsutism; Hyperandrogenism; Contraceptives, Oral, Combined; Ethinyl Estradiol; Cyproterone Acetate; Testosterone
PubMed: 37440702
DOI: 10.1093/ejendo/lvad082 -
Sleep Medicine Reviews Dec 2022Sleep disturbance is a common clinical concern throughout the menopausal transition. However, the pathophysiology and causes of these sleep disturbances remain poorly... (Review)
Review
Sleep disturbance is a common clinical concern throughout the menopausal transition. However, the pathophysiology and causes of these sleep disturbances remain poorly understood, making it challenging to provide appropriate therapy. Our goal was to i) review the literature about the influence of ovarian hormones on sleep in perimenopausal women, ii) summarize the potential underlying pathophysiology of menopausal sleep disturbances and iii) evaluate the implications of these findings for the therapeutic approach to sleep disturbances in the context of menopause. A systematic literature search using the databases Embase, MEDLINE and Cochrane Library was conducted. Keywords relating to ovarian hormones, sleep disturbances and menopause were used. Ultimately, 86 studies were included. Study Quality Assessment Tools of the National Institutes of Health were used for quality assessment. Results from good-quality studies demonstrated that the postmenopausal decline in estrogen and progesterone contributes to sleep disturbances in women and that timely treatment with estrogen and/or progesterone therapy improved overall sleep quality. Direct and indirect effects of both hormones acting in the central nervous system and periphery, as well as via secondary effects (e.g. reduction in vasomotor symptoms), can contribute to improvements in sleep. To strengthen external validity, studies examining neurobiological pathways are needed.
Topics: United States; Female; Humans; Progesterone; Sleep; Estrogens
PubMed: 36356400
DOI: 10.1016/j.smrv.2022.101710 -
Frontiers in Neuroendocrinology Jan 2021Increasing evidence indicates that ovarian hormones affect brain structure, chemistry and function of women in their reproductive age, potentially shaping their behavior... (Review)
Review
Increasing evidence indicates that ovarian hormones affect brain structure, chemistry and function of women in their reproductive age, potentially shaping their behavior and mental health. Throughout the reproductive years, estrogens and progesterone levels fluctuate across the menstrual cycle and can modulate neural circuits involved in affective and cognitive processes. Here, we review seventy-seven neuroimaging studies and provide a comprehensive and data-driven evaluation of the accumulating evidence on brain plasticity associated with endogenous ovarian hormone fluctuations in naturally cycling women (n = 1304). The results particularly suggest modulatory effects of ovarian hormones fluctuations on the reactivity and structure of cortico-limbic brain regions. These findings highlight the importance of performing multimodal neuroimaging studies on neural correlates of systematic ovarian hormone fluctuations in naturally cycling women based on careful menstrual cycle staging.
Topics: Brain; Estrogens; Female; Humans; Menstrual Cycle; Neuroimaging; Progesterone
PubMed: 33098847
DOI: 10.1016/j.yfrne.2020.100878 -
Medicine Aug 2023Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases, laparoscopic fertility preservation surgery is considered a common treatment for EMT. The present study aimed to evaluate the efficacy and safety of dienogest, leuprolide, danazol, gestrinone, mifepristone and levonorgestrel intrauterine system (LNG-IUS) in relieving symptoms and delaying the recurrence of EMT cysts after fertility protection surgery.
METHODS
We searched PubMed, the Cochrane Library, Web of Science, EMBase, China National Knowledge Infrastructure, VIP Database, China Biology Medicine disc, WanFang Data databases to collect randomized controlled trials (RCT) related to dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS as a follow-up treatment after fertility preserving surgery for EMT. After literature screening, data extraction and quality evaluation, effective rate, recurrence rate, pregnancy rate and adverse reaction rate were used as outcome indicators to evaluate the efficacy and safety of drugs. Evidence networks included in the study were drawn and publication bias was assessed. The drugs most likely to be the best postoperative treatment were explored through mixed comparison of different drugs and efficacy ranking.
RESULT
Effective rate: dienogest, leprerelin, gestrinone and LNG-IUS were better than placebo after EMT fertility preservation surgery; dienogest was superior to mifepristone and danazol. LNG-IUS is superior to danazol. LNG-IUS has the highest potential for improving the effectiveness of EMT symptoms. Recurrence rate: the application of dienogest, leuprolide, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was lower than that of placebo; dienogest and LNG-IUS were lower than danazol. The recurrence rate of dinorgestrel was the last place with the highest performance. Pregnancy rate: in the cases with fertility requirements, dienogest and,leuprolide were better than placebo after EMT fertility preservation surgery; dienogest was superior to danazol, gestrinone and mifepristone. Leuprolide is superior to danazol and gestrinone. The first rank of dienogest pregnancy rate was the highest. Adverse reaction rate: the application of dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was higher than that of placebo. After placebo, LNG-IUS had the highest adverse reaction rate.
CONCLUSION
For patients after fertility preserving surgery for EMT, the recurrence rate of dienogest was the last place with highest preference. The first rank of dienogest pregnancy was the highest.
Topics: Female; Humans; Endometriosis; Danazol; Gestrinone; Leuprolide; Mifepristone; Network Meta-Analysis; Levonorgestrel
PubMed: 37543781
DOI: 10.1097/MD.0000000000034496 -
Frontiers in Endocrinology 2023Polycystic ovary syndrome (PCOS) is a common endocrinopathy causing infertility in childbearing women. Progestin-primed ovarian stimulation (PPOS) protocol has recently... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Polycystic ovary syndrome (PCOS) is a common endocrinopathy causing infertility in childbearing women. Progestin-primed ovarian stimulation (PPOS) protocol has recently been used for infertile women. However, whether PPOS provides a significant benefit over gonadotropin-releasing hormone (GnRH) analogue protocols in PCOS is still controversial. The objective of this systematic review is to investigate the efficacy of PPOS in patients with PCOS during fertilization (IVF) or intracytoplasmic sperm injection (ICSI). We searched Medline, Embase, Google Scholar, ClinicalTrials, and Cochrane Central Register of Controlled Trials from inception to April 1, 2023. Randomized controlled trials (RCTs) and observational studies comparing the efficacy between PPOS and conventional GnRH analogue protocols in patients with PCOS in English were included. The primary outcomes included live birth rate, the incidence of moderate or severe ovarian hyperstimulation syndrome (OHSS), and the number of metaphase II oocytes. The pooled estimates were calculated using the random-effects models as odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CIs). Three RCTs and six cohort studies involving 2289 patients were included. Results from RCTs suggest that PPOS leads to no significant difference in the risk of OHSS, the number of metaphase II oocytes, or the rate of live birth when compared to GnRH analogue protocols. The pooling estimates of cohort studies showed consistent results. Additionally, in cohort studies, PPOS required a higher dose of Gn and tended to improve the implantation rate, clinical pregnancy rate, and ongoing pregnancy rate. For subgroup analyses, the higher implantation rate, clinical pregnancy rate, and ongoing pregnancy rate were found in PPOS compared to the GnRH agonist short protocol. However, the certainty of the evidence for the outcomes was generally low. Overall, There is currently no evidence to support that PPOS could reduce the risk of OHSS, increase oocyte maturation, or improve pregnancy outcomes in women with PCOS undergoing IVF/ICSI when compared to GnRH analogue protocols. Considering its efficiency and safety, this protocol could be a patient-friendly and viable alternative for PCOS patients, especially when frozen-thawed embryo transfer is planned. Future high-quality randomized trials with children's long-term safety and cost-effective analyses are still required.
SYSTEM REVIEW REGISTRATION
NPLASY (202340059). https://inplasy.com/inplasy-2023-4-0059/.
Topics: Female; Humans; Pregnancy; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Progestins; Steroids
PubMed: 37795363
DOI: 10.3389/fendo.2023.1224858 -
Cancers Aug 2020Menopausal hormone therapy (MHT) is an appropriate treatment for women with the climacteric syndrome. The estrogen component of MHT effectively alleviates climacteric... (Review)
Review
BACKGROUND
Menopausal hormone therapy (MHT) is an appropriate treatment for women with the climacteric syndrome. The estrogen component of MHT effectively alleviates climacteric symptoms but also stimulates the endometrium and thus may increase the risk of endometrial cancer (EC).
MATERIALS AND METHODS
We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify controlled and uncontrolled clinical trials reporting on the prevalence and/or incidence of EC among women using MHT.
RESULTS
31 publications reporting on 21,306 women with EC diagnosed during or after MHT were identified. A significantly reduced risk of EC among continuous-combined (cc)MHT users with synthetic progestins (SPs) was demonstrated in 10/19 studies with odds ratios (ORs)/hazard ratios (HRs) between 0.24 and 0.71. Only one study documented an increased risk of EC among long-term users (≥10 years), not confirmed in three other sub-group analyses of women with ≥6, ≥5, and >10 years of ccMHT use. A significantly increased risk of EC among users of sequential-combined (sc)MHT with SPs was demonstrated in 6/12 studies with ORs/HRs between 1.38 and 4.35. Number of days of progestin per month was a significant modulator of EC risk. A decreased risk of EC was seen in obese women. Two studies documented an increased risk of EC among users of cc/scMHT with micronized progesterone. A significantly increased risk of EC among estrogen-only MHT users was demonstrated in 9/12 studies with ORs/HRs between 1.45 and 4.46. The adverse effect of estrogen-only MHT was greatest among obese women.
CONCLUSION
ccMHT with SPs reduces the risk of EC, whereas estrogen-only MHT increases the risk. scMHT with SPs and cc/scMHT with micronized progesterone increase the risk of EC depending on type of progestin, progestin dosage, and duration of MHT use.
PubMed: 32781573
DOI: 10.3390/cancers12082195 -
Nicotine & Tobacco Research : Official... Oct 2022It is established that higher prediagnostic circulating androgen and estrogen levels are associated with increased breast cancer risk in premenopausal and postmenopausal... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
It is established that higher prediagnostic circulating androgen and estrogen levels are associated with increased breast cancer risk in premenopausal and postmenopausal women. Pooled analyses in postmenopausal women report higher androgen and estrogen levels in current heavy cigarette smokers compared to nonsmokers. However, evidence among premenopausal women has been inconsistent.
AIMS AND METHODS
We conducted a systematic review and meta-analysis to estimate differences in standardized mean hormone levels among current premenopausal smokers compared to nonsmokers. We reviewed and collated publications with sex hormone levels by smoking status among healthy, premenopausal women who were nonusers of exogenous hormones, including oral contraceptives, using PubMed through December 2019. A random effects meta-analysis was conducted to combine the standardized mean differences (SMD) and 95% confidence intervals (CIs) for estradiol, progesterone, testosterone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and sex hormone-binding globulin by smoking status. Findings were summarized by menstrual cycle phase and overall.
RESULTS
Nineteen published peer-reviewed articles were included. Significantly increased testosterone levels among smokers compared to nonsmokers were identified from cross-sectional studies with varied menstrual phase timing (SMD 0.14; 95% CI 0.0005, 0.29) and significantly increased dehydroepiandrosterone-sulfate levels were found over all phases (SMD 0.12; 95% CI 0.01, 0.22). However, substantial heterogeneity existed in these studies.
CONCLUSIONS
This meta-analysis suggests that smoking may increase blood androgen levels in healthy premenopausal women which may increase breast cancer risk; however, the differences were modest. Larger and covariate-adjusted studies with standardized collection over the menstrual cycle are needed to better understand this relationship and to reduce heterogeneity.
IMPLICATIONS
Existing research has described associations between high prediagnostic estradiol and androgen levels with breast cancer risk among premenopausal women and has established active smoking as a breast cancer risk factor. However, the smoking and circulating sex hormone associations among premenopausal women remain inadequately studied. In this meta-analysis, we identified an association between smoking and higher mean testosterone and dehydroepiandrosterone-sulfate levels with consideration of menstrual phase, providing additional information on smoking's potential pathway to premenopausal breast cancer.
Topics: Female; Humans; Sex Hormone-Binding Globulin; Androgens; Progesterone; Cross-Sectional Studies; Gonadal Steroid Hormones; Estradiol; Testosterone; Breast Neoplasms; Estrogens; Smoking; Dehydroepiandrosterone; Contraceptives, Oral; Sulfates
PubMed: 35291014
DOI: 10.1093/ntr/ntac066 -
Cells May 2023Deep endometriosis (DE) is the most severe subtype of endometriosis, with the hallmark of lesions infiltrating adjacent tissue. Abnormal vascularisation has been... (Review)
Review
Deep endometriosis (DE) is the most severe subtype of endometriosis, with the hallmark of lesions infiltrating adjacent tissue. Abnormal vascularisation has been implicated in contributing to endometriosis lesion development in general, and how vascularisation influences the pathogenesis of DE, in particular, is of interest. This systematic review followed the PRISMA guidelines to elucidate and examine the evidence for DE-specific vascularisation. A literature search was performed using MEDLINE, Embase, PubMed, Scopus, Cochrane CENTRAL Library and Europe PubMed Central databases. The databases were searched from inception to the 13 March 2023. A total of 15 studies with 1125 patients were included in the review. The DE lesions were highly vascularised, with a higher microvessel density (MVD) than other types of endometriotic lesions, eutopic endometrium from women with endometriosis and control tissue. Vascular endothelial growth factor, its major subtype (VEGF-A) and associated receptor (VEGFR-2) were significantly increased in the DE lesions compared to superficial endometriosis, eutopic endometrium and control tissue. Progestin therapy was associated with a significant decrease in the MVD of the DE lesions, explaining their therapeutic effect. This review comprehensively summarises the available literature, reporting abnormal vascularisation to be intimately related to the pathogenesis of DE and presents potentially preferential therapeutic targets for the medical management of DE.
Topics: Humans; Female; Endometriosis; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Neovascularization, Pathologic; Endometrium
PubMed: 37174718
DOI: 10.3390/cells12091318 -
Advances in Therapy Nov 2022Although several studies suggest beneficial effects of low-dose estrogen-progestins (LEPs) and progestins on dysmenorrhea in Japanese women, the difference in efficacy... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Although several studies suggest beneficial effects of low-dose estrogen-progestins (LEPs) and progestins on dysmenorrhea in Japanese women, the difference in efficacy between drugs remains unknown.
METHODS
We identified studies by searching the MEDLINE, Cochrane Library, and ICHUSHI databases and included randomized controlled trials (RCTs) that used total dysmenorrhea score and visual analogue scale (VAS) as outcome measures to evaluate LEPs and progestins for primary and secondary dysmenorrhea. We analyzed results by meta-analysis and network meta-analysis (NMA).
RESULTS
We identified 10 articles on eight RCTs and included seven drugs (six LEPs and one progestin, i.e., dienogest) and placebo in the analysis. Meta-analysis showed improvements in total dysmenorrhea score and VAS for almost all drugs compared with placebo. In NMA, VAS in secondary dysmenorrhea improved more with dienogest than with norethisterone/ethinylestradiol (mean difference - 25.84 [95% CrI - 44.46 to - 7.15]). In the comparison of administration regimens, VAS improved more with progestin-continuous than LEP-cyclic and the surface under the cumulative ranking (SUCRA) of LEP-extended and progestin-continuous appeared to be higher than that of LEP-cyclic.
CONCLUSIONS
We confirmed that LEPs and dienogest are effective for primary and secondary dysmenorrhea and suggest that continuous regimens may be more effective than cyclic regimens in improving outcomes.
Topics: Dysmenorrhea; Estrogens; Female; Gastrointestinal Diseases; Humans; Japan; Network Meta-Analysis; Norethindrone; Progestins
PubMed: 36048405
DOI: 10.1007/s12325-022-02298-9