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Human Reproduction Update Aug 2022Globally, the ages at pubertal onset for girls and boys have been decreasing during recent decades, partly attributed to excess body fat accumulation. However, a growing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Globally, the ages at pubertal onset for girls and boys have been decreasing during recent decades, partly attributed to excess body fat accumulation. However, a growing body of literature has recognized that endocrine disrupting chemicals (EDCs) may play an important role in this global trend, but the association has not yet been fully established.
OBJECTIVE AND RATIONALE
EDCs can interfere with normal hormone function and metabolism and play a role in pubertal onset. We aimed to systematically identify and evaluate the current evidence on the timing of pubertal onset in girls and boys following prenatal or postnatal exposures to xenobiotic EDCs.
SEARCH METHODS
Following PRISMA guidelines, we performed a systematic literature search of original peer-reviewed publications in the PubMed database through a block search approach using a combination of index MeSH and free text search terms. Publications were considered if they covered biomarkers of prenatal or postnatal exposures to xenobiotic EDCs (European Commission's list of category 1 EDCs) measured in maternal or child biospecimen and pubertal onset defined by the progression of the following milestones (and assessed in terms of the following measures): menarche (age), thelarche (Tanner staging) and pubarche (Tanner staging), in girls, and genital stage (Tanner staging), testicular volume (ml) and pubarche (Tanner staging), in boys.
OUTCOMES
The literature search resulted in 703 references, of which we identified 52 publications fulfilling the eligibility criteria for the qualitative trend synthesis and 23 publications for the meta-analysis. The qualitative trend synthesis provided data on 103 combinations of associations between prenatal or postnatal exposure to EDC compounds groups and puberty outcomes and the meta-analysis enabled 18 summary risk estimates of meta-associations.
WIDER IMPLICATIONS
Statistically significant associations in the qualitative trend synthesis suggested that postnatal exposure to phthalates may be associated with earlier thelarche and later pubarche. However, we did not find consistent evidence in the meta-analysis for associations between timing of pubertal onset in girls and boys and exposures to any of the studied xenobiotic EDCs. We were not able to identify specific pre- or postnatal windows of exposure as particularly critical and susceptible for effects of EDCs. Current evidence is subject to several methodological challenges and inconsistencies and evidence on specific exposure-outcome associations remains too scarce to firmly confirm EDC exposure as a risk factor for changes in age of pubertal onset in the general child population. To create a more uniform foundation for future comparison of evidence and to strengthen pooled studies, we recommend the use of more standardized approaches in the choice of statistical analyses, with exposure transformations, and in the definitions and assessments of puberty outcomes. The impact of mixtures of EDC exposures on the association also remains unestablished and would be valuable to elucidate for prenatal and postnatal windows of exposure. Future large, longitudinal epidemiological studies are needed to clarify the overall association.
Topics: Child; Endocrine Disruptors; Female; Humans; Longitudinal Studies; Male; Menarche; Pregnancy; Puberty; Xenobiotics
PubMed: 35466359
DOI: 10.1093/humupd/dmac013 -
Frontiers in Endocrinology 2023Fertility preservation is an important healthcare focus in the paediatric and adolescent population when gonadotoxic treatments are required. Ovarian stimulation (OS)...
BACKGROUND
Fertility preservation is an important healthcare focus in the paediatric and adolescent population when gonadotoxic treatments are required. Ovarian stimulation (OS) resulting in oocyte cryopreservation is a well-established fertility preservation option in the adult population. It's utility, however, is little known in young patients. The purpose of this review was to synthesise the available literature on OS in patients ≤18 years old, to identify gaps in current research and provide suggestions for future research directions.
METHODS
Using PRISMA guidelines, a systematic review of the literature was performed for all relevant full-text articles published in English in Medline, Embase, the Cochrane Library and Google Scholar databases. The search strategy used a combination of subject headings and generic terms related to the study topic and population. Two reviewers independently screened studies for eligibility, extracted data and assessed the risk of bias. Characteristics of the studies, objectives and key findings were extracted and summarised in a narrative synthesis.
RESULTS
Database search and manual review identified 922 studies, 899 were eliminated based on defined exclusion criteria. Twenty-three studies were included and comprised 468 participants aged ≤18 years who underwent OS (median 15.2, range 7-18 years old). Only three patients were premenarchal, and four patients were on treatment to suppress puberty. Patients had OS for a broad range of indications including oncology treatment, transgender care and Turner syndrome. A total of 488 cycles of OS were completed, with all but 18 of these cycles (96.3%) successfully resulting in cryopreserved mature oocytes (median 10 oocytes, range 0-35). Fifty-three cycles (9.8%) were cancelled. Complications were rare (<1%). One pregnancy was reported from a female who had OS aged 17 years old.
CONCLUSION
This systematic review demonstrates that OS and oocyte cryopreservation is achievable in young females however there are only a few cases in the literature describing OS in premenarcheal children or those who have suppressed puberty. There is little proof that OS can lead to pregnancy in adolescents, and no proof that this can be achieved in premenarchal girls. Therefore it should be regarded as an innovative procedure for adolescents and experimental for premenarcheal girls.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=265705, identifier CRD42021265705.
Topics: Pregnancy; Female; Male; Humans; Transgender Persons; Sexual Maturation; Cryopreservation; Oocytes; Ovulation Induction
PubMed: 37404308
DOI: 10.3389/fendo.2023.1146476 -
Pituitary Dec 2022Giant prolactinoma (GP) in childhood and adolescence is a rare entity with scarce literature. We aimed to describe clinical features, biochemistry, radiology, genetics,...
PURPOSE
Giant prolactinoma (GP) in childhood and adolescence is a rare entity with scarce literature. We aimed to describe clinical features, biochemistry, radiology, genetics, management, and outcome in pediatric (≤ 20 years) GP.
METHODS
Retrospective record review of 18 pediatric GP patients from our center and systematic review including these and 77 from the literature (total cohort: 95).
RESULTS
GP constituted 20% of our pediatric prolactinoma cohort. In the total cohort (age: 15.4 ± 3.5 years), the majority (77, 82.8%) were males. Mass effect symptoms (88.6%), and pubertal delay/arrest in males (82.1%) were frequent. Median basal prolactin was 8649 (3246-17,532) ng/ml and the maximum tumor dimension was 5.5 ± 1.5 cm. MEN1 and AIP mutations were noted in 7 (21.9%) and 6 (18.8%) patients, respectively. Males with central hypogonadism had baseline bi-testicular volume of 20.2 ± 8.4 cc, lower LH than FSH (-2.04 ± 0.9 vs. -0.7 ± 1.6 SDS, p = 0.0075), and mostly, normal inhibin B. Majority (49/76, 64.5%) received dopamine agonist (DA) as first-line treatment with additional therapy in 35% (17/49). DA monotherapy arm had less frequent central hypothyroidism (42.9% vs 87.1%, p = 0.002) and central adrenal insufficiency (7.1% vs 66.7%, p = 0.0003) than multimodal therapy. A smaller tumor dimension (4.7 vs. 5.7 cm, p = 0.04) was associated with normoprolactinemia on DA monotherapy and AIP mutations (33.3% vs. nil, p = 0.02) with multimodal therapy.
CONCLUSION
GP is characterized by male predominance with frequent delay/arrest of puberty (82%), but relative sparing of the FSH-inhibin B axis in boys. DA monotherapy may be preferred as the first-line therapy in pediatric GP.
Topics: Adolescent; Child; Female; Humans; Male; Dopamine Agonists; Follicle Stimulating Hormone; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies
PubMed: 35851929
DOI: 10.1007/s11102-022-01250-y -
Clinical Endocrinology Mar 2023P450 side-chain cleavage deficiency (SCCD) patients present with primary adrenal insufficiency (PAI) with or without undervirilized external genitalia. The distinction...
OBJECTIVE
P450 side-chain cleavage deficiency (SCCD) patients present with primary adrenal insufficiency (PAI) with or without undervirilized external genitalia. The distinction between classic and nonclassic steroidogenic acute regulatory protein deficiency has been described, whereas in SCCD is unclear. The data on gonadal function and its correlation with SCCD genotype has not been studied. We describe our experience and perform a systematic review of genetically proven SCCD patients to determine the distinct phenotypic and genotypic characteristics of 46,XY SCCD patients with typical male external genitalia (SCCD-TMG) and atypical (SCCD-AG) external genitalia.
DESIGN, PATIENTS AND MEASUREMENTS
Retrospective review of three genetically proven SCCD patients from our centre and per-patient data analysis from a systematic review of 52 probands was performed. SCCD-TMG (n = 19) was defined as external genitalia of Sinnecker score 1 with 46,XY karyotype; the rest (Sinnecker 2-5) were classified as SCCD-AG (n = 15).
RESULTS
We report two new Indian cases of SCCD with three novel likely pathogenic variants and pubertal follow-up of a previously reported patient. In systematic review, age at diagnosis of PAI and elevated renin were not different between 46,XY SCCD-TMG (n = 19) and SCCD-AG (n = 15), whereas spontaneous puberty (9/9 vs. 0/3, p = .0045), normal prepubertal (5/5 vs. 6/6, p = .002), pubertal gonadotropins (2/9 vs. 0/3, p = 1) and normal pubertal testosterone (9/11 vs. 0/3, p = .027) were more common in SCCD-TMG. Testicular adrenal rest tumours were exclusive to SCCD-TMG (n = 4). SCCD-TMG was associated with four particular genotypes [monoallelic p.Glu314Lys with another deleterious variant on the second allele (p.Glu314Lys/X-CHS: X-compound heterozygous state), biallelic p.Arg451Trp, p.Phe215Ser/p.Arg232Ter and monoallelic p.Val79Ile]. 46,XX SCCD patients with p.Glu314Lys/X-CHS also had normal gonadotropins with spontaneous puberty.
CONCLUSION
SCCD-TMG is associated with four specific genotypes and distinct gonadal characteristics from SCCD-AG with overlapping features of PAI.
Topics: Humans; Male; Testosterone; Puberty; Testicular Neoplasms; Mutation
PubMed: 36357326
DOI: 10.1111/cen.14848 -
Journal of Human Reproductive Sciences 2022Reproduction remains a vital characteristic of living things necessary for survival and continuity. Specific brain regions and structures are responsible for regulating... (Review)
Review
Reproduction remains a vital characteristic of living things necessary for survival and continuity. Specific brain regions and structures are responsible for regulating the different aspects of human reproduction. This study systematically reviewed the brain regions that play structural, hormonal and physiological roles in controlling the various aspects of human reproduction from puberty, sexual function, gametogenesis, childbirth and fertility to infertility to inform advancement in research and therapeutic interventions in human reproductive disorders. A systematic literature search of online databases (MEDLINE, Europe PMC and Google Scholar) was made using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for observational and cross-sectional studies providing evidence for the role(s) of the brain region in human reproduction from the year 2011-2021. Out of 141 articles found, 15 studies met the inclusion criteria, including six cross-sectional and nine randomised controlled trials. The study acknowledged the roles of the pituitary gland, hypothalamus and pineal gland, widely known for regulating the human reproductive system in a gender-based approach while highlighting essential gaps and opportunities for future research. This review provides a 10-year update and overview of the role of different brain regions in human reproduction and will stimulate future research in human reproduction.
PubMed: 35928473
DOI: 10.4103/jhrs.jhrs_18_22 -
Urologic Oncology Jul 2022The incidence and outcomes of bladder cancer (BCa) have apparent sex differences. Various observational studies have demonstrated that the age of menarche might be... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The incidence and outcomes of bladder cancer (BCa) have apparent sex differences. Various observational studies have demonstrated that the age of menarche might be associated with female BCa. To explore this relationship, a meta-analysis and systematic review were performed based on available studies.
MATERIAL AND METHODS
A systematic search was performed in PubMed, Embase, and Web of Science for studies published up to October 1, 2021. Two reviewers independently extracted related data between age of menarche and BCa risk from the included studies. The Newcastle-Ottawa quality assessment scale was applied to evaluate the quality of the studies. The relative risk (RR) ratio and its 95% confidence interval (CI) were then calculated.
RESULTS
A total of 12 studies containing 3,719 BCa cases and 1,350,207 women, were included in this meta-analysis. The pooled data showed that the age of menarche was not significantly associated with BCa risk (RR = 0.96, 95% CI: 0.85-1.08), although the evidence was of moderate quality. Similar results were observed in case-control (RR = 1.33, 95% CI = 0.77-2.21) and cohort studies (RR = 0.95, 95% CI = 0.84-1.07). Moreover, subgroup analyses based on study quality, population, exposure assessment, and several potential important confounders and risk factors revealed similar results. No evidence of publication bias and significant heterogeneity was found among these studies. Furthermore, a random-effects dose-response meta-regression model was established, which revealed negative results.
CONCLUSIONS
Our findings suggested that the age of menarche was not associated with BCa risk in women. However, these findings needed to be further confirmed given the limitations and potential biases.
Topics: Case-Control Studies; Female; Humans; Male; Menarche; Odds Ratio; Risk Factors; Urinary Bladder Neoplasms
PubMed: 35400567
DOI: 10.1016/j.urolonc.2022.02.022 -
Environmental Research Nov 2020To identify the association between phenolic chemicals and the risk of earlier puberty based on the available evidence by systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To identify the association between phenolic chemicals and the risk of earlier puberty based on the available evidence by systematic review and meta-analysis.
METHODS
Databases PubMed, Web of Science, and Cochrane Library were searched and retrieved appropriate journal articles on the association between phenols exposure and earlier puberty in children published before February 14, 2020. Stata software version 12.0 and Excel were used for statistical analysis.
RESULTS
Nine studies were included in the meta-analysis with total subjects of 4737. All the subjects included in our studies were girls. The pooled estimate has shown the association between 2, 5- dichrolophenol exposure, and earlier puberty in children with effect size (ES) 1.13 (95% CI: 1.06, 1.20). Exposed to other types of phenolic chemicals such as bisphenol A, Triclosan, Benzophenone-3 were not statistically significant associated with the risk of earlier puberty in children with the overall pooled estimates of ES of 1.09 (95%CI: 0.88, 1.35), ES 1.05(95% CI: 0.96, 1.15), and ES 0.98 (95% CI: 0.88, 1.10) respectively.
CONCLUSION
Our results portray that phenols particularly 2, 5- dichlorophenol exposure might be associated with the risk of earlier puberty in children. Also, caution should be taken to other type of phenolic chemicals since in subgroup analysis some individual studies have shown a positive relationship between bisphenol A, Triclosan and Benzophenone-3 exposures, and the risk of earlier puberty in children. Future cohort studies should be conducted with more sample sizes to determine the relationship between 2, 5- dichlorophenol, and the risk of earlier puberty in children of all gender.
Topics: Child; Cohort Studies; Female; Humans; Phenols; Puberty; Puberty, Precocious; Triclosan
PubMed: 32805251
DOI: 10.1016/j.envres.2020.110056 -
Journal of Pediatric Urology Feb 2022Knowledge of the normal size of the urethral meatus in boys is important for safely performing urethral catheterization and fundamental to the diagnosis and treatment of... (Review)
Review
INTRODUCTION
Knowledge of the normal size of the urethral meatus in boys is important for safely performing urethral catheterization and fundamental to the diagnosis and treatment of paediatric urological conditions. However, clinicians often rely subjectively on previous experience and clinical judgement, rather than a robust evidence-base. A systematic review of the literature was undertaken to define the calibre of the male urethral meatus in paediatric age-groups.
METHODS
The MEDLINE and EMBASE databases were systematically searched from inception to December 2020 for studies measuring meatal calibre in boys up to 16 years of age. Google Scholar searches along with forward and backward citation tracking identified additional studies. Studies of subjects >16 years, females, or patients with urethral diseases were excluded.
RESULTS
Nine articles (2084 paediatric subjects) were included in the final review. Mean meatal calibre increases non-linearly with age, with accelerated growth occurring during infancy (mini-puberty) and adolescence (puberty). Meatal calibre can be approximately grouped by age as follows: neonate (6-10Fr); infant (10-12Fr); child (12-14Fr); and adolescent (14-18Fr). There is substantial individual variability for same-aged children. Meatal calibre has been independently related to height, weight, and penile size, but the effects of ethnicity and circumcision remain unclear.
CONCLUSIONS
The evidence-base for this fundamental aspect of paediatric urology includes only a few low-quality studies and is largely derived from one early study of circumcised American boys. Further studies are warranted to establish normative urethral size values based on rigorous, contemporary data with known dependent variables also included.
Topics: Adolescent; Child; Child, Preschool; Circumcision, Male; Humans; Infant; Infant, Newborn; Male; Nomograms; Urethra; Urethral Diseases; Urinary Catheterization
PubMed: 34782235
DOI: 10.1016/j.jpurol.2021.10.014 -
Dermatologic Surgery : Official... Jun 2024Striae are fine lines on the body that occur following rapid skin stretching (i.e., following pregnancy, puberty, weight change). The aim of this systematic review was...
BACKGROUND
Striae are fine lines on the body that occur following rapid skin stretching (i.e., following pregnancy, puberty, weight change). The aim of this systematic review was to assess the current literature on treatment outcomes associated with striae.
OBJECTIVE
(1) To assess the efficacy and safety of different treatment options reported for striae and (2) to determine the most efficient treatment options for each subtype of striae.
METHODS
A systematic search was performed on MEDLINE, Embase, and PubMed with no publication date or language restrictions. All articles with original data and treatment outcomes were included.
RESULTS
One hundred fifty-one studies on the treatment of striae met inclusion criteria (83% female, mean age at diagnosis = 30.2), and 4,806 treatment outcomes of striae were described. Energy-based devices were the most reported modality (56%; n = 2,699/4,806), followed by topicals (19%; n = 919/4,806) and combinations (12%; n = 567/4,806). The highest rates of complete response were injection-based devices for striae distensae (7%; n = 12/172), CO 2 lasers for striae alba (4%; n = 12/341), and platelet-rich plasma injections for striae rubra (31%; n = 4/13).
CONCLUSION
Treatment options for striae are varied, likely indicating a lack of effective treatments due to the diversity in striae subtypes. Improved outcomes in striae management may be achieved with additional research on factors that predict treatment response.
Topics: Female; Humans; Laser Therapy; Striae Distensae; Treatment Outcome; Male
PubMed: 38452322
DOI: 10.1097/DSS.0000000000004151 -
Children (Basel, Switzerland) Nov 2023Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age and female adolescents. The diagnosis of PCOS is difficult during... (Review)
Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age and female adolescents. The diagnosis of PCOS is difficult during puberty due to overlapping of the criteria with normal variations of menstruation during this age period. There are insufficient data on the gut microbiome and PCOS and potential mechanisms linking the two. The present systematic review aimed to detect dysbiosis patterns in youth with PCOS, compared with healthy controls.
METHODS
One hundred seventy-eight studies were identified by a databases search and sixty-eight by a full-text assessment for eligibility; four were included in the systematic review and underwent quality control.
RESULTS
The results of the study were controversial in accordance to findings from the literature. A change in gut microbiome α diversity was found in PCOS adolescents, with no significant alterations in β diversity. Almost all studies found Firmicutes, Bacteroidetes, and Actinobacteria in abundance in both groups, with changes in family composition and fluctuations at the phylum level. A statistically significant association between these changes and clinical or biochemical features of the syndrome was described.
CONCLUSIONS
This systematic review confirmed gut microbiota dysbiosis in youth with PCOS. However, further data are needed to clarify these changes and to build a strategy to prevent the syndrome.
PubMed: 38136074
DOI: 10.3390/children10121872