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The Cochrane Database of Systematic... Oct 2022Premature ovarian insufficiency (POI) is a clinical syndrome resulting from loss of ovarian function before the age of 40. It is a state of hypergonadotropic... (Review)
Review
BACKGROUND
Premature ovarian insufficiency (POI) is a clinical syndrome resulting from loss of ovarian function before the age of 40. It is a state of hypergonadotropic hypogonadism, characterised by amenorrhoea or oligomenorrhoea, with low ovarian sex hormones (oestrogen deficiency) and elevated pituitary gonadotrophins. POI with primary amenorrhoea may occur as a result of chromosomal and genetic abnormalities, such as Turner syndrome, Fragile X, or autosomal gene defects; secondary amenorrhoea may be iatrogenic after the surgical removal of the ovaries, radiotherapy, or chemotherapy. Other causes include autoimmune diseases, viral infections, and environmental factors; in most cases, POI is idiopathic. Appropriate replacement of sex hormones in women with POI may facilitate the achievement of near normal uterine development. However, the optimal effective hormone therapy (HT) regimen to maximise the reproductive potential for women with POI remains unclear.
OBJECTIVES
To investigate the effectiveness and safety of different hormonal regimens on uterine and endometrial development in women with POI.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in September 2021. We also checked references of included studies, and contacted study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) investigating the effect of various hormonal preparations on the uterine development of women diagnosed with POI.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. The primary review outcome was uterine volume; secondary outcomes were endometrial thickness, endometrial histology, uterine perfusion, reproductive outcomes, and any reported adverse events.
MAIN RESULTS
We included three studies (52 participants analysed in total) investigating the role of various hormonal preparations in three different contexts, which deemed meta-analysis unfeasible. We found very low-certainty evidence; the main limitation was very serious imprecision due to small sample size. Conjugated oral oestrogens versus transdermal 17ß-oestradiol We are uncertain of the effect of conjugated oral oestrogens compared to transdermal 17ß-oestradiol (mean difference (MD) -18.2 (mL), 95% confidence interval (CI) -23.18 to -13.22; 1 RCT, N = 12; very low-certainty evidence) on uterine volume, measured after 12 months of treatment. The study reported no other relevant outcomes (including adverse events). Low versus high 17ß-oestradiol dose We are uncertain of the effect of a lower dose of 17ß-oestradiol compared to a higher dose of 17ß-oestradiol on uterine volume after three or five years of treatment, or adverse events (1 RCT, N = 20; very low-certainty evidence). The study reported no other relevant outcomes. Oral versus vaginal administration of oestradiol and dydrogesterone We are uncertain of the effect of an oral or vaginal administration route on uterine volume and endometrial thickness after 14 or 21 days of administration (1 RCT, N = 20; very low-certainty evidence). The study reported no other relevant outcomes (including adverse events).
AUTHORS' CONCLUSIONS
No clear conclusions can be drawn in this systematic review, due to the very low-certainty of the evidence. There is a need for pragmatic, well designed, randomised controlled trials, with adequate power to detect differences between various HT regimens on uterine growth, endometrial development, and pregnancy outcomes following the transfer of donated gametes or embryos in women diagnosed with POI.
Topics: Amenorrhea; Dydrogesterone; Endometrium; Estradiol; Estrogens; Female; Humans; Menopause, Premature; Pregnancy
PubMed: 36200708
DOI: 10.1002/14651858.CD008209.pub2 -
Nutrients Dec 2021Bisphenol A (BPA) is an endocrine-disrupting chemical widely used in plastic products that may have an adverse effect on several physiologic functions in children. The... (Review)
Review
BACKGROUND
Bisphenol A (BPA) is an endocrine-disrupting chemical widely used in plastic products that may have an adverse effect on several physiologic functions in children. The aim of this systematic review is to summarize the current knowledge of the impact of BPA concentrations on thyroid function in neonates, children, and adolescents.
METHODS
A systematic search of Medline, Scopus, Clinical Trials.gov, Cochrane Central Register of Controlled Trials CENTRAL, and Google Scholar databases according to PRISMA guidelines was performed. Only case-control, cross-sectional, and cohort studies that assessed the relationship between Bisphenol A and thyroid function in neonates and children aged <18 years were included. Initially, 102 articles were assessed, which were restricted to 73 articles after exclusion of duplicates. A total of 73 articles were assessed by two independent researchers based on the title/abstract and the predetermined inclusion and exclusion criteria. According to the eligibility criteria, 18 full-text articles were selected for further assessment. Finally, 12 full-text articles were included in the present systematic review.
RESULTS
The presented studies offer data that suggest a negative correlation of BPA concentrations with TSH in children, a gender-specific manner of action, and a potential effect on proper neurodevelopment. However, the results are inconclusive with respect to specific thyroid hormone concentrations and the effect on thyroid autoimmunity.
CONCLUSION
The potential negative effect of BPA in the developing thyroid gland of children that may affect proper neurodevelopment, suggesting the need to focus future research on designing studies that elucidate the underlying mechanisms and the effects of BPA in thyroid function in early life.
Topics: Adolescent; Age Factors; Autoimmunity; Benzhydryl Compounds; Child; Child, Preschool; Endocrine Disruptors; Female; Humans; Infant; Infant, Newborn; Male; Phenols; Thyroid Gland; Thyrotropin
PubMed: 35011041
DOI: 10.3390/nu14010168 -
European Journal of Endocrinology Jan 2024Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical treatment with testosterone promotes virilization but not testicular growth or spermatogenesis. To quantify treatment practices and efficacy, we systematically reviewed all studies investigating gonadotropins for the achievement of pubertal outcomes in males with hypogonadotropic hypogonadism.
DESIGN
Systematic review and meta-analysis.
METHODS
A systematic review of Medline, Embase, Global Health, and PsycINFO databases in December 2022. Risk of Bias 2.0/Risk Of Bias In Non-randomized Studies of Interventions/National Heart, Lung, and Blood Institute tools for quality appraisal. Protocol registered on PROSPERO (CRD42022381713).
RESULTS
After screening 3925 abstracts, 103 studies were identified including 5328 patients from 21 countries. The average age of participants was <25 years in 45.6% (n = 47) of studies. Studies utilized human chorionic gonadotropin (hCG) (n = 93, 90.3% of studies), human menopausal gonadotropin (n = 42, 40.8%), follicle-stimulating hormone (FSH) (n = 37, 35.9%), and gonadotropin-releasing hormone (28.2% n = 29). The median reported duration of treatment/follow-up was 18 months (interquartile range 10.5-24 months). Gonadotropins induced significant increases in testicular volume, penile size, and testosterone in over 98% of analyses. Spermatogenesis rates were higher with hCG + FSH (86%, 95% confidence interval [CI] 82%-91%) as compared with hCG alone (40%, 95% CI 25%-56%). However, study heterogeneity and treatment variability were high.
CONCLUSIONS
This systematic review provides convincing evidence of the efficacy of gonadotropins for pubertal induction. However, there remains substantial heterogeneity in treatment choice, dose, duration, and outcomes assessed. Formal guidelines and randomized studies are needed.
Topics: Humans; Male; Chorionic Gonadotropin; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Hypogonadism; Klinefelter Syndrome; Spermatogenesis; Testis; Testosterone; Young Adult
PubMed: 38128110
DOI: 10.1093/ejendo/lvad166 -
The Cochrane Database of Systematic... Oct 2021Conventional treatment of X-linked hypophosphatemia with oral phosphate and calcitriol can heal rickets, but it does not always raise serum phosphate concentrations... (Review)
Review
BACKGROUND
Conventional treatment of X-linked hypophosphatemia with oral phosphate and calcitriol can heal rickets, but it does not always raise serum phosphate concentrations significantly, nor does it always normalize linear growth. Some clinical trials suggest that combining recombinant human growth hormone therapy with conventional treatment improves growth velocity, phosphate retention, and bone mineral density, but some clinical trials suggest that it appears to aggravate the pre-existent disproportionate stature of such children. This is an updated version of a previously published review.
OBJECTIVES
To determine whether recombinant human growth hormone therapy for children with X-linked hypophosphatemia is associated with changes in longitudinal growth, mineral metabolism, endocrine function, renal function, bone mineral density, body proportions, and also with any adverse effects.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. In addition, we searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE and the reference lists of identified trials and other reviews. We also undertook some additional handsearching of relevant journals and conference proceedings. Date of the most recent search: 12 January 2021 SELECTION CRITERIA: All randomized controlled studies or quasi-randomized controlled studies comparing growth hormone (alone or combined with conventional treatment) with either placebo or conventional treatment alone in children with X-linked hypophosphatemia.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for risk of bias and extracted data from eligible studies. GRADE criteria were used to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included two studies (20 participants) in the review. In one cross-over study, results showed that recombinant human growth hormone therapy may improve the height standard deviation (SDS) score (z score), but we are unsure whether the intervention was the reason behind a transient increase in serum phosphate and tubular maximum for phosphate reabsorption. In the second, parallel study, treatment may also have improved the height SDS from baseline in the rhGH group compared to the control group, although no significant difference was seen between groups after three years, MD 0.50 SDS (95 % CI -0.54 to 1.54) (low-certainty evidence). The treatment was possibly well-tolerated during both studies with only transient adverse effects seen in three participants (low-certainty evidence). We are uncertain whether growth hormone improves serum phosphate levels or change in TmP/GFR (very low-certainty evidence). The treatment may make little or no difference to alkaline phosphatase levels (low-certainty evidence).
AUTHORS' CONCLUSIONS
We do not have enough high-certainty evidence to recommend the use of recombinant human growth hormone therapy in children with X-linked hypophosphatemia.
Topics: Body Height; Child; Cross-Over Studies; Familial Hypophosphatemic Rickets; Growth Hormone; Human Growth Hormone; Humans
PubMed: 34618915
DOI: 10.1002/14651858.CD004447.pub3 -
Therapeutic Advances in Medical Oncology 2023The use of antibody-drug conjugates for the treatment of advanced-stage human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer (BC) has shown...
BACKGROUND
The use of antibody-drug conjugates for the treatment of advanced-stage human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer (BC) has shown prominent curative effects, which has led to increased academic interest. However, the role of HER2-low expression in the prognosis of BC remains controversial.
METHODS
We conducted a systematic search of the PubMed, Embase, and Cochrane library databases and several oncology conferences until 20 September 2022. We used fixed- and random-effects models to calculate odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and pathological complete response (pCR) rates.
RESULTS
Overall, 26 studies encompassing 677,248 patients were included in the meta-analysis. Patients with HER2-low BC showed significantly better OS than those with HER2-zero BC in the overall population (HR = 0.90; 95% CI: 0.85-0.97) and hormone receptor-positive population (HR = 0.98; 95% CI: 0.96-0.99), whereas no significant difference was observed in the OS of the hormone receptor-negative population ( > 0.05). In addition, there was no significant difference in the DFS of the overall and hormone receptor-negative population ( > 0.05), but better DFS than those with HER2-zero BC in the hormone receptor-negative population (HR = 0.96; 95% CI: 0.94-0.99). There was also no significant difference in the PFS of the overall population, hormone receptor-positive, and hormone receptor-negative population ( > 0.05). Patients with HER2-low BC had a lower pCR rate after neoadjuvant treatment than those with HER2-zero BC.
CONCLUSIONS
Compared to patients with HER2-zero BC, those with HER2-low BC had better OS in the overall population and hormone receptor-positive population, DFS in hormone receptor-positive population and lower pCR in the overall population. The biological differences between HER2-low and HER2-zero BCs, particularly in hormone receptor-positive patients, and the relationship between HER2-low expression status and prognosis need to be explored further.
PubMed: 36872948
DOI: 10.1177/17588359231156669 -
Annals of Global Health Jun 2021Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients' anemia and lifespan, but it may lead to iron overload in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients' anemia and lifespan, but it may lead to iron overload in parenchymal tissue organs and endocrine glands that cause their dysfunctions as the iron regulatory system can't excrete excess iron from the bloodstream.
OBJECTIVE
To evaluate the prevalence of iron-related complications (short stature, growth retardation, and growth hormone deficiency) in β-thalassemia major (TM) patients.
METHODS
We performed an electronic search in PubMed, Scopus, and Web of Sciences to evaluate the prevalence of growth hormone impairment in β-thalassemia major (TM) patients worldwide. Qualities of eligible studies were assessed by the Joanna Briggs Institute checklist for the prevalence study. We used Comprehensive Meta-Analysis (Version 2) to calculate the event rate with 95% CIs, using a random-effects model for all analyses.
FINDINGS
Seventy-four studies were included from five continents between 1978 and 2019; 70.27% (Asia), 16.21% (Europe), 6.75% (Africa), 2.70% (America), 1.35% (Oceania), and 2.70% (Multicenter). The overall mean age of the participants was about 14 years. The pooled prevalence of short stature (ST) was 48.9% (95% CI 35.3-62.6) and in male was higher than female (61.9%, 95% CI 53.4-69.7 vs. 50.9%, CI 41.8-59.9). The pooled prevalence of growth retardation (GR) was 41.1% and in male was higher than in female (51.6%, 95% CI 17.8-84 vs. 33.1%, CI 9.4-70.2). The pooled prevalence of growth hormone deficiency (GHD) was 26.6% (95% CI 16-40.8).
CONCLUSION
Our study revealed that near half of thalassemia patients suffer from growth impairments. However, regular evaluation of serum ferritin levels, close monitoring in a proper institute, suitable and acceptable treatment methods besides regular chelation therapy could significantly reduce the patients' complications.
Topics: Adolescent; Blood Transfusion; Body Height; Dwarfism; Endocrine System Diseases; Female; Humans; Iron Overload; Male; beta-Thalassemia
PubMed: 34164261
DOI: 10.5334/aogh.3184 -
Frontiers in Endocrinology 2023Growth hormone (GH) affects metabolism and regulates growth in childhood. The most prominent feature of GH deficiency (GHD) in children is diminished height velocity...
BACKGROUND
Growth hormone (GH) affects metabolism and regulates growth in childhood. The most prominent feature of GH deficiency (GHD) in children is diminished height velocity that eventually leads to short stature. In adult-onset GHD, lean body mass (LBM) is reduced, and visceral fat mass (FM) increased. Beneficial effects of GH treatment on body composition in adults with GHD, including an increase in muscle mass and a decrease in FM, are well established. Relatively few studies have investigated the effects of GH treatment on the body composition of pediatric patients with idiopathic or hypothalamic-pituitary disease-associated GH deficiency. This systematic review aimed to summarize available evidence relating to the effects of GH treatment on body composition in children with GHD.
METHODS
The PubMed, Science Direct, Cochrane Trials, and Embase databases, were searched with keywords including "GH", "body composition", "children", and "growth hormone" for English-language articles, published between January 1999 and March 2021. Two reviewers independently evaluated the search results and identified studies for inclusion based on the following criteria: participants had a confirmed diagnosis of GHD (as defined in each study); participants were pediatric patients who were receiving GH or had stopped GH treatment, regardless of whether they were pre- or post-pubertal; the intervention was recombinant human GH (rhGH; somatropin); and outcomes included changes in body composition during or after stopping GH therapy. Data extracted from each study included study quality, study sample characteristics, study interventions, and body composition. Data on fat-free mass and LBM were combined into a single category of LBM.
RESULTS
Sixteen studies reporting changes in body composition (i.e., FM and LBM) associated with GH treatment in children with GHD were identified and included in the review. Collectively, these studies demonstrated that FM decreased, and LBM increased in response to GH replacement therapy.
CONCLUSION
Despite study limitations (i.e., potential effects of diet and physical activity were not considered), we concluded that a periodic body composition assessment is required to ensure that a satisfactory body composition is achieved during GH replacement therapy in children with GHD.
Topics: Child; Humans; Body Composition; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Hypopituitarism
PubMed: 36843617
DOI: 10.3389/fendo.2023.1093691 -
Neuroendocrinology 2023Idiopathic hypothalamic dysfunction (IHD) is a rare syndrome with heterogeneous clinical symptoms. This study aimed to systematically review the clinical features and...
INTRODUCTION
Idiopathic hypothalamic dysfunction (IHD) is a rare syndrome with heterogeneous clinical symptoms. This study aimed to systematically review the clinical features and potential treatment of IHD based on our case series and literature.
METHODS
We analysed six recently diagnosed cases of IHD in Peking Union Medical College Hospital and conducted a systematic review of IHD case studies published before August 25, 2021, using the PubMed/Medline database. All 12 articles that met the definition of IHD and provided individual clinical data were reviewed.
RESULTS
Of the 19 cases reviewed (13 from the literature and 6 from our centre), the median age at onset was 6 years. Obesity/weight gain (n = 14, 73.7%) and electrolyte abnormalities (n = 14, 73.7%) were the most common hypothalamic physiological dysfunction, followed by autonomic dysregulation (n = 13, 68.4%) and adipsia (n = 13, 68.4%). The most common initial symptom of young patients was obesity/weight gain, whereas the initial symptoms of the three adult patients were hypothalamic amenorrhoea, delayed sexual development, and polydipsia. 11 (57.9%) patients had obesity, and three of our patients were diagnosed with metabolic syndrome in late adolescence or early adulthood. Three of our cases diagnosed with growth hormone deficiency received growth hormone therapy, which exerted positive effects on growth promotion and weight stabilization.
CONCLUSION
Although obesity/weight gain was the most common symptom of IHD, uncommon initial symptoms such as electrolyte abnormalities and sexual disorders also require attention, especially in patients with late childhood- or adult-onset IHD. Consistent monitoring of metabolic profiles is recommended. Positive effects of growth hormone replacement therapy on growth and weight were observed, but more extensive cohort studies are required to confirm its efficacy and safety.
Topics: Adult; Adolescent; Humans; Child; Obesity; Weight Gain; Hypothalamic Diseases; Growth Hormone; Electrolytes
PubMed: 36746124
DOI: 10.1159/000529537 -
Diagnostics (Basel, Switzerland) Jun 2023Growth-hormone (GH)- and prolactin (PRL)-secreting PitNETs (pituitary neuroendocrine tumors) are divided into multiple histological subtypes, which determine their... (Review)
Review
Growth-hormone (GH)- and prolactin (PRL)-secreting PitNETs (pituitary neuroendocrine tumors) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Proliferation markers alone have a questionable degree of prediction, so we try to identify validated prognostic models as accurately as possible. (1) Background: The data available so far show that the use of staging and clinical-pathological classification of PitNETs, along with imaging, are useful in predicting the evolution of these tumors. So far, there is no consensus for certain markers that could predict tumor evolution. The application of the WHO (World Health Organisation) classification in practice needs to be further evaluated and validated. (2) Methods: We performed the CRD42023401959 protocol in Prospero with a systematic literature search in PubMed and Web of Science databases and included original full-text articles (randomized control trials and clinical trials) from the last 10 years, published in English, and the search used the following keywords: (i) pituitary adenoma AND (prognosis OR outcome OR prediction), (ii) growth hormone pituitary adenoma AND (prognosis OR outcome OR prediction), (iii) prolactin pituitary adenoma AND (prognosis OR outcome OR prediction); (iv) mammosomatotroph adenoma AND (prognosis OR outcome OR prediction). (3) Results: Two researchers extracted the articles of interest and if any disagreements occurred in the selection process, these were settled by a third reviewer. The articles were then assessed using the ROBIS bias assessment and 75 articles were included. (4) Conclusions: the clinical-pathological classification along with factors such as GH, IGF-1, prolactin levels both preoperatively and postoperatively offer valuable information.
PubMed: 37371013
DOI: 10.3390/diagnostics13122118 -
Toxicological Sciences : An Official... Jul 2022Phthalates are ubiquitous compounds known to leach from the plastic products that contain them. Due to their endocrine-disrupting properties, a wide range of studies...
Phthalates are ubiquitous compounds known to leach from the plastic products that contain them. Due to their endocrine-disrupting properties, a wide range of studies have elucidated their effects on reproduction, metabolism, neurodevelopment, and growth. Additionally, their impacts during pregnancy and on the developing fetus have been extensively studied. Most recently, there has been interest in the impacts of phthalates on the placenta, a transient major endocrine organ critical to maintenance of the uterine environment and fetal development. Phthalate-induced changes in placental structure and function may have significant impacts on the course of pregnancy and ultimately, child health. Prior reviews have described the literature on phthalates and placental health; however to date, there has been no comprehensive, systematic review on this topic. Here, we review 35 papers (24 human and 11 animal studies) and summarize phthalate exposures in relation to an extensive set of placental measures. Phthalate-related alterations were reported for placental morphology, hormone production, vascularization, histopathology, and gene/protein expression. The most consistent changes were observed in vascular and morphologic endpoints, including cell composition. These changes have implications for pregnancy complications such as preterm birth and intrauterine growth restriction as well as potential ramifications for children's health. This comprehensive review of the literature, including common sources of bias, will inform the future work in this rapidly expanding field.
Topics: Animals; Child; Female; Humans; Infant, Newborn; Models, Animal; Phthalic Acids; Placenta; Pregnancy; Premature Birth
PubMed: 35686923
DOI: 10.1093/toxsci/kfac060