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Journal of Assisted Reproduction and... Mar 2023To investigate the possibility that altered actions of endogenous progesterone affect receptivity and contribute to unexplained infertility (UI). (Meta-Analysis)
Meta-Analysis
PURPOSE
To investigate the possibility that altered actions of endogenous progesterone affect receptivity and contribute to unexplained infertility (UI).
METHODS
Two authors electronically searched MEDLINE, CINAHL and Embase databases from inception to 6 July 2022 and hand-searched according to Cochrane methodology. We included all published primary research reporting outcomes related to endogenous progesterone in natural cycles in women with UI. Studies were assessed for risk of bias using a modified Newcastle-Ottawa Score or NHLBI Score. We pooled results where appropriate using a random-effects model. Findings were reported as odds ratios or mean differences.
RESULTS
We included 41 studies (n = 4023). No difference was found between the mid-luteal serum progesterone levels of women with UI compared to fertile controls (MD 0.74, - 0.31-1.79, I 36%). Women with UI had significantly higher rates of 'out-of-phase' endometrium than controls. Nine out of 10 progesterone-mediated markers of endometrial receptivity were significantly reduced in women with UI compared to fertile controls (the remaining 1 had conflicting results). Resistance in pelvic vessels was increased and perfusion of the endometrium and sub-endometrium reduced in UI compared to fertile controls in all included studies. Progesterone receptor expression and progesterone uptake were also reduced in women with unexplained infertility.
CONCLUSIONS
End-organ measures of endogenous progesterone activity are reduced in women with UI compared to fertile controls. This apparently receptor-mediated reduction in response affects endometrial receptivity and is implicated as the cause of the infertility. Further research is required to confirm whether intervention could overcome this issue, offering a new option for treating unexplained infertility.
TRIAL REGISTRATION
PROSPERO registration: CRD42020141041 06/08/2020.
Topics: Female; Humans; Progesterone; Infertility, Female; Endometrium; Corpus Luteum
PubMed: 36572790
DOI: 10.1007/s10815-022-02689-5 -
Neuroscience and Biobehavioral Reviews Feb 2023Sex steroid hormones play an important role in fetal development, brain functioning and neuronal protection. Growing evidence highlights the positive effects of these... (Meta-Analysis)
Meta-Analysis
Sex steroid hormones play an important role in fetal development, brain functioning and neuronal protection. Growing evidence highlights the positive effects of these hormones against brain damage induced by neonatal hypoxia-ischemia (HI). This systematic review with meta-analysis aims to verify the efficacy of sex steroid hormones in preventing HI-induced brain damage in rodent models. The protocol was registered at PROSPERO and a total of 22 articles were included. Moderate to large effects were observed in HI animals treated with sex steroid hormones in reducing cerebral infarction size and cell death, increasing neuronal survival, and mitigating neuroinflammatory responses and astrocyte reactivity. A small effect was evidenced for cognitive function, but no significant effect for motor function; moreover, a high degree of heterogeneity was observed. In summary, data suggest that sex steroid hormones, such as progesterone and 17β estradiol, improve morphological and cellular outcomes following neonatal HI. Further research is paramount to examine neurological function during HI recovery and standardization of methodological aspects is imperative to reduce the risk of spurious findings.
Topics: Animals; Animals, Newborn; Brain; Estradiol; Gonadal Steroid Hormones; Hypoxia-Ischemia, Brain; Ischemia; Progesterone
PubMed: 36572200
DOI: 10.1016/j.neubiorev.2022.105018 -
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 -
Reviews in Endocrine & Metabolic... Apr 2023Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity... (Review)
Review
Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity can unravel pathophysiologic mechanisms and identify individuals at risk of adverse clinical outcomes. The literature was systematically reviewed to identify periconceptional biomarkers of the endocrine, inflammatory and one-carbon metabolic pathways influenced by maternal obesity. A search was conducted in Embase, Ovid Medline All, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases, complemented by manual search in PubMed until December 31, 2020. Eligible studies were those that measured biomarker(s) in relation to maternal obesity, overweight/obesity or body mass index (BMI) during the periconceptional period (14 weeks preconception until 14 weeks post conception). The ErasmusAGE score was used to assess the quality of included studies. Fifty-one articles were included that evaluated over 40 biomarkers. Endocrine biomarkers associated with maternal obesity included leptin, insulin, thyroid stimulating hormone, adiponectin, progesterone, free T4 and human chorionic gonadotropin. C-reactive protein was associated with obesity as part of the inflammatory pathway, while the associated one-carbon metabolism biomarkers were folate and vitamin B12. BMI was positively associated with leptin, C-reactive protein and insulin resistance, and negatively associated with Free T4, progesterone and human chorionic gonadotropin. Concerning the remaining studied biomarkers, strong conclusions could not be established due to limited or contradictory data. Future research should focus on determining the predictive value of the optimal set of biomarkers for their use in clinical settings. The most promising biomarkers include leptin, adiponectin, human chorionic gonadotropin, insulin, progesterone and CRP.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Leptin; C-Reactive Protein; Obesity, Maternal; Adiponectin; Progesterone; Obesity; Biomarkers; Insulin; Chorionic Gonadotropin; Carbon
PubMed: 36520252
DOI: 10.1007/s11154-022-09762-5 -
The Cochrane Database of Systematic... Dec 2022Preterm birth (PTB), defined as birth prior to 37 weeks of gestation, occurs in ten percent of all pregnancies. PTB is responsible for more than half of neonatal and... (Review)
Review
BACKGROUND
Preterm birth (PTB), defined as birth prior to 37 weeks of gestation, occurs in ten percent of all pregnancies. PTB is responsible for more than half of neonatal and infant mortalities and morbidities. Because cervical insufficiency is a common cause of PTB, one possible preventive strategy involves insertion of a cervical pessary to support the cervix. Several published studies have compared the use of pessary with different management options and obtained questionable results. This highlights the need for an up-to-date systematic review of the evidence.
OBJECTIVES
To evaluate the benefits and harms of cervical pessary for preventing preterm birth in women with singleton pregnancies and risk factors for cervical insufficiency compared to no treatment, vaginal progesterone, cervical cerclage or bedrest.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform to 22 September 2021. We also searched the reference lists of included studies for additional records.
SELECTION CRITERIA
We included published and unpublished randomised controlled trials (RCTs) comparing cervical pessary with no treatment, vaginal progesterone, cervical cerclage or bedrest for preventing PTB. We excluded quasi-randomised trials. Our primary outcome was delivery before 34 weeks' gestation. Our secondary outcomes were 1. delivery before 37 weeks' gestation, 2. maternal mortality, 3. maternal infection or inflammation, 4. preterm prelabour rupture of membranes, 5. harm to woman from the intervention, 6. maternal medications, 7. discontinuation of the intervention, 8. maternal satisfaction, 9. neonatal/paediatric care unit admission, 10. fetal/infant mortality, 11. neonatal sepsis, 12. gestational age at birth, 13. harm to offspring from the intervention 14. birthweight, 15. early neurodevelopmental morbidity, 15. late neurodevelopmental morbidity, 16. gastrointestinal morbidity and 17. respiratory morbidity.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for eligibility and risk of bias, evaluated trustworthiness based on criteria developed by the Cochrane Pregnancy and Childbirth Review Group, extracted data, checked for accuracy and assessed certainty of evidence using the GRADE approach.
MAIN RESULTS
We included eight RCTs (2983 participants). We included five RCTs (1830 women) in the comparison cervical pessary versus no treatment, three RCTs (1126 pregnant women) in the comparison cervical pessary versus vaginal progesterone, and one study (13 participants) in the comparison cervical pessary versus cervical cerclage. Overall, the certainty of evidence was low to moderate due to inconsistency (statistical heterogeneity), imprecision (few events and wide 95% confidence intervals (CIs) consistent with possible benefit and harm), and risk of performance and detection bias. Cervical pessary versus no treatment Cervical pessary compared with no treatment may reduce the risk of delivery before 34 weeks (risk ratio (RR) 0.72, 95% CI 0.33 to 1.55; 5 studies, 1830 women; low-certainty evidence) or before 37 weeks (RR 0.68, 95% CI 0.44 to 1.05; 5 studies, 1830 women; low-certainty evidence). However, these results should be viewed with caution because the 95% CIs cross the line of no effect. Cervical pessary compared with no treatment probably has little or no effect on the risk of maternal infection or inflammation (RR 1.04, 95% CI 0.87 to 1.26; 2 studies, 1032 women; moderate-certainty evidence). It is unclear if cervical pessary compared with no treatment has an effect on neonatal/paediatric care unit admission (RR 0.96, 95% CI 0.58 to 1.59; 3 studies, 1332 infants; low-certainty evidence) or fetal/neonatal mortality (RR 0.93, 95% CI 0.58 to 1.48; 5 studies, 1830 infants; low-certainty evidence) because the 95% CIs are compatible with a wide range of effects that encompass both appreciable benefit and harm. Cervical pessary versus vaginal progesterone Cervical pessary may reduce the risk of delivery before 34 weeks (RR 0.72, 95% CI 0.52 to 1.02; 3 studies, 1126 women; moderate-certainty evidence) or before 37 weeks (RR 0.89, 95% CI 0.73 to 1.09; 3 studies, 1126 women; moderate-certainty evidence), but we are uncertain of the results because the 95% CI crosses the line of no effect. The intervention probably has little or no effect on maternal infection or inflammation (RR 0.95, 95% CI 0.81 to 1.12; 2 studies, 265 women; moderate-certainty evidence). It is unclear if cervical pessary compared with vaginal progesterone has an effect on the risk of neonatal/paediatric care unit admission (RR 0.98, 95% CI 0.49 to 1.98; low-certainty evidence) or fetal/neonatal mortality (RR 1.97, 95% CI 0.50 to 7.70; 2 studies; 265 infants; low-certainty evidence) because the 95% CIs are compatible with a wide range of effects that encompass both appreciable benefit and harm. Cervical pessary versus cervical cerclage Only one very small study of 13 pregnant women contributed data to this comparison; the results were unclear.
AUTHORS' CONCLUSIONS
In women with a singleton pregnancy, cervical pessary compared with no treatment or vaginal progesterone may reduce the risk of delivery before 34 weeks or 37 weeks, although these results should be viewed with caution due to uncertainty around the effect estimates. There is insufficient evidence with regard to the effect of cervical pessary compared with cervical cerclage on PTB. Due to low certainty-evidence in many of the prespecified outcomes and non-reporting of several other outcomes of interest for this review, there is a need for further robust RCTs that use standardised terminology for maternal and offspring outcomes. Future trials should take place in a range of settings to improve generalisability of the evidence. Further research should concentrate on comparisons of cervical pessary versus cervical cerclage and bed rest. Investigation of different phenotypes of PTB may be relevant.
Topics: Female; Pregnancy; Humans; Pessaries; Cervix Uteri; Progesterone; Premature Birth; Cerclage, Cervical
PubMed: 36453699
DOI: 10.1002/14651858.CD014508 -
Developmental Neuroscience 2023Hypoxic-ischaemic encephalopathy (HIE) in the newborn baby is a major contributor to neonatal mortality and morbidity across the world. Therapeutic hypothermia (TH) is... (Review)
Review
Hypoxic-ischaemic encephalopathy (HIE) in the newborn baby is a major contributor to neonatal mortality and morbidity across the world. Therapeutic hypothermia (TH) is the current standard treatment for moderate to severe HIE, but not all babies benefit. Potential neuroprotective actions of progesterone (PROG) include anti-apoptotic, anti-inflammatory, and anti-oxidative effects and reduction of energy depletion, tissue/cellular oedema, and excitotoxicity. In pre-clinical studies of neonatal HIE, PROG has neuroprotective properties but has not been the subject of systematic review. Here, our objective was to evaluate the evidence base for PROG as a potential therapeutic agent in HIE. The PICO framework was used to define the following inclusion criteria. Population: human neonates with HIE/animal models of HIE; intervention: PROG +/- other agents; comparison: V.S. control; outcome: pathological, neurobehavioural, and mechanistic outcome measures. Medline, EMBASE, and CINHAL were then searched between August to October 2018 using pre-defined medical subject heading and keywords. Study inclusion, data extraction, and risk of bias (ROB) analysis using the SYRCLE ROB tool were carried out by two authors. 14 studies were included in the review. They typically displayed a high ROB. This systematic review suggests that PROG reduced neuropathology and reduced neurobehavioural deficits post-hypoxic-ischaemic (HI) insult in 8 and 3 studies, respectively. However, there was sex dimorphism in the effects of PROG. In addition, there are limitations and biases in these studies, and there remains a need for well-designed large pre-clinical studies with greater methodological quality to further inform the efficacy, safety, dose, timing, and frequency of PROG administration. With such data, large animal studies could be planned combining PROG administration with and without TH.
Topics: Animals; Infant, Newborn; Humans; Neuroprotective Agents; Hypoxia-Ischemia, Brain; Progesterone; Hypothermia, Induced; Neuroprotection
PubMed: 36436500
DOI: 10.1159/000521540 -
Archives of Gynecology and Obstetrics Jan 2023Endometriosis is a common chronic gynecological disease defined as the presence of endometrial glands and stroma tissue outside the uterus. Gestrinone is an effective... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Endometriosis is a common chronic gynecological disease defined as the presence of endometrial glands and stroma tissue outside the uterus. Gestrinone is an effective antiestrogen that induces endometrial atrophy and/or amenorrhea. The purpose of this systematic review is to provide an evaluation of safety and effectiveness of gestrinone for the treatment of endometriosis.
METHODS
We performed a search in six electronic databases: PubMed, MEDLINE (ovid), Embase, Cochrane CENTRAL (clinical trials), Web of Science and Scopus. Our selected primary outcomes were the changes in dysmenorrhea, pain relief including pelvic pain and dyspareunia. The secondary outcomes embrace hormones parameters, pregnancy rate and adverse events.
RESULTS
Of 3269 references screened, 16 studies were included involving 1286 women. All studies compared gestrinone with other drugs treatments (placebo, Danazol, Mifepristone tablets, Leuprolide acetate, Quyu Jiedu Recipe) during 6 months. When compared with other drugs treatments, gestrinone relieved dysmenorrhea, pelvic pain, and morphologic response in the ovary. There was an increase on the pregnancy rate. Regarding the side effects observed, gestrinone showed the same adverse events and increased the risk of acne and seborrhea when compared to other treatments. Even if there was any difference in efficacy between gestrinone, danazol, leuprolide acetate, or Quyu Jiedu Recipe Chinese Medicine, it remains unclear due to insufficient data.
CONCLUSION
Based limited evidence available suggests that gestrinone appeared to be safe and may have some efficacy advantages over danazol, as well as other therapeutic interventions for treating endometriosis. However, this conclusion should be interpreted with caution, due the quality of the evidence provided is generally very low or unclear.
TRIAL REGISTRATION
CRD42021284148.
Topics: Pregnancy; Female; Humans; Endometriosis; Gestrinone; Danazol; Leuprolide; Dysmenorrhea; Pelvic Pain
PubMed: 36434439
DOI: 10.1007/s00404-022-06846-0 -
Maturitas Jan 2023Women with premature ovarian insufficiency (POI) are exposed to a long period of estrogenic deficiency, which potentially brings higher health risks, especially... (Review)
Review
INTRODUCTION
Women with premature ovarian insufficiency (POI) are exposed to a long period of estrogenic deficiency, which potentially brings higher health risks, especially regarding bone health. We performed a systematic review of the literature to evaluate the effect of hormone therapy (HT) on bone mineral density (BMD) in women with POI.
MATERIALS AND METHODS
A systematic search was performed of the MEDLINE and EMBASE databases up to September 2021. We included studies that analyzed women with idiopathic (spontaneous) POI treated with HT, and those who had BMD evaluated. Analysis of risk of bias of studies selected was performed.
RESULTS
We found 335 articles and selected 16 studies according to the inclusion criteria. Most of the studies revealed lower bone density in both the femoral neck and lumbar spine of women with POI compared with healthy women. Bone mass had the tendency to remain stable in women treated with estrogen + progestin therapy. However, in women already with bone mass loss, the therapy - in the doses most frequently used - was not able to revert the loss. Higher doses of estrogen seem to have a positive impact on BMD, as did combined oral contraceptives used continuously. Also, the interruption of HT for longer than one year was linked to significant bone loss.
CONCLUSION
Although HT brings clear benefits, further studies are needed to establish its long-term effects, as well as doses and formulations with better protective effects on the bone mass of these women.
Topics: Female; Humans; Bone Density; Menopause, Premature; Primary Ovarian Insufficiency; Estrogens; Hormone Replacement Therapy
PubMed: 36368093
DOI: 10.1016/j.maturitas.2022.09.011 -
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 -
JAMA Nov 2022It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers.
Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
IMPORTANCE
It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers.
OBJECTIVE
To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions.
DATA SOURCES
PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries from January 1, 2016, through October 12, 2021; surveillance through July 2022.
STUDY SELECTION
English-language randomized clinical trials and prospective cohort studies of fair or good quality.
DATA EXTRACTION AND SYNTHESIS
Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available.
MAIN OUTCOMES AND MEASURES
Morbidity and mortality related to chronic conditions; health-related quality of life.
RESULTS
Twenty trials (N = 39 145) and 3 cohort studies (N = 1 155 410) were included. Participants using estrogen only compared with placebo had significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]) per 10 000 persons. Risks per 10 000 persons were statistically significantly increased for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). Participants using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 persons, for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). Risks, per 10 000 persons, were significantly increased for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia (179 vs 91 cases; 88 more [95% CI, 15-212]) over 4.0 years; and urinary incontinence (1707 vs 1145 cases; 562 more [95% CI, 412-726]) over 1 year.
CONCLUSIONS AND RELEVANCE
Use of hormone therapy in postmenopausal persons for the primary prevention of chronic conditions was associated with some benefits but also with an increased risk of harms.
Topics: Female; Humans; Advisory Committees; Chronic Disease; Estrogens; Fractures, Bone; Hormone Replacement Therapy; Hormones; Postmenopause; Primary Prevention; Progestins; Prospective Studies; Quality of Life; Risk Assessment; United States; Urinary Incontinence; Venous Thromboembolism
PubMed: 36318128
DOI: 10.1001/jama.2022.18324