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Frontiers in Endocrinology 2023Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital...
BACKGROUND
Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital heart disease, renal anomalies, lymphatic malformations, chest deformities, cryptorchidism in males.
METHODS
In this narrative review, we summarized the available data on puberty and gonadal function in NS subjects and the role of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway in fertility. In addition, we have reported our personal experience on pubertal development and vertical transmission in NS.
CONCLUSIONS
According to the literature and to our experience, NS patients seem to have a delay in puberty onset compared to the physiological timing reported in healthy children. Males with NS seem to be at risk of gonadal dysfunction secondary not only to cryptorchidism but also to other underlying developmental factors including the MAP/MAPK pathway and genetics. Long-term data on a large cohort of males and females with NS are needed to better understand the impact of delayed puberty on adult height, metabolic profile and well-being. The role of genetic counselling and fertility related-issues is crucial.
Topics: Male; Child; Adult; Female; Humans; Noonan Syndrome; Cryptorchidism; Gonads; Puberty; Mitogen-Activated Protein Kinases
PubMed: 37576960
DOI: 10.3389/fendo.2023.1213098 -
PLOS Global Public Health 2023It is unclear whether the literature on adolescent gender dysphoria (GD) provides evidence to inform clinical decision making adequately. In the final of a series of...
It is unclear whether the literature on adolescent gender dysphoria (GD) provides evidence to inform clinical decision making adequately. In the final of a series of three papers, we sought to review published evidence systematically regarding the types of treatment being implemented among adolescents with GD, the age when different treatment types are instigated, and any outcomes measured within adolescence. Having searched PROSPERO and the Cochrane library for existing systematic reviews (and finding none at that time), we searched Ovid Medline 1946 -October week 4 2020, Embase 1947-present (updated daily), CINAHL 1983-2020, and PsycInfo 1914-2020. The final search was carried out on 2nd November 2020 using a core strategy including search terms for 'adolescence' and 'gender dysphoria' which was adapted according to the structure of each database. Papers were excluded if they did not clearly report on clinically-likely gender dysphoria, if they were focused on adult populations, if they did not include original data (epidemiological, clinical, or survey) on adolescents (aged at least 12 and under 18 years), or if they were not peer-reviewed journal publications. From 6202 potentially relevant articles (post deduplication), 19 papers from 6 countries representing between 835 and 1354 participants were included in our final sample. All studies were observational cohort studies, usually using retrospective record review (14); all were published in the previous 11 years (median 2018). There was significant overlap of study samples (accounted for in our quantitative synthesis). All papers were rated by two reviewers using the Crowe Critical Appraisal Tool v1·4 (CCAT). The CCAT quality ratings ranged from 71% to 95%, with a mean of 82%. Puberty suppression (PS) was generally induced with Gonadotropin Releasing Hormone analogues (GnRHa), and at a pooled mean age of 14.5 (±1.0) years. Cross Sex Hormone (CSH) therapy was initiated at a pooled mean of 16.2 (±1.0) years. Twenty-five participants from 2 samples were reported to have received surgical intervention (24 mastectomy, one vaginoplasty). Most changes to health parameters were inconclusive, except an observed decrease in bone density z-scores with puberty suppression, which then increased with hormone treatment. There may also be a risk for increased obesity. Some improvements were observed in global functioning and depressive symptoms once treatment was started. The most common side effects observed were acne, fatigue, changes in appetite, headaches, and mood swings. Adolescents presenting for GD intervention were usually offered puberty suppression or cross-sex hormones, but rarely surgical intervention. Reporting centres broadly followed established international guidance regarding age of treatment and treatments used. The evidence base for the outcomes of gender dysphoria treatment in adolescents is lacking. It is impossible from the included data to draw definitive conclusions regarding the safety of treatment. There remain areas of concern, particularly changes to bone density caused by puberty suppression, which may not be fully resolved with hormone treatment.
PubMed: 37552651
DOI: 10.1371/journal.pgph.0001478 -
American Journal of Obstetrics and... Dec 2023We conducted a systematic review and meta-analysis of the effects of Mediterranean diet on female reproductive health outcomes over the life-course. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We conducted a systematic review and meta-analysis of the effects of Mediterranean diet on female reproductive health outcomes over the life-course.
DATA SOURCES
We searched PubMed, Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov to identify eligible studies published till February 2022. Eligible references from identified studies and review articles were also considered.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials, prospective cohort studies, or nested case-control studies examining Mediterranean diet and major female reproductive outcomes over the lifespan, including clinical outcomes from childhood to adulthood (menarche, polycystic ovary syndrome, endometriosis, and outcomes related to fertility, pregnancy, and menopause), were included for review.
METHODS
Two independent reviewers screened and performed data extraction and risk-of-bias assessment. We performed random-effects meta-analysis to obtain summary relative risks and 95% confidence intervals for major female reproductive outcomes. Subgroup analyses were performed for several pregnancy outcomes according to timing of the interventions for randomized controlled trials and timing of the dietary assessment for observational studies.
RESULTS
Thirty-two studies (9 randomized controlled trials, 22 prospective cohort studies, and 1 nested case-control study) involving 103,204 predominantly White women (>95%) were included. The pooled relative risk (95% confidence interval) comparing randomization to Mediterranean diet vs a control diet based on 7 randomized controlled trials was 0.74 (0.55-0.99) for gestational diabetes mellitus, 0.45 (0.26-0.76) for preterm birth, 0.71 (0.51-1.00) for gestational hypertension, and 0.82 (0.54-1.22) for preeclampsia; the effect sizes for preterm birth were greater in randomized controlled trials that initiated the interventions in first trimester vs after first trimester (P heterogeneity=.02). We observed inverse associations for all the above-mentioned pregnancy outcomes based on 9 cohort studies. There was suggestive evidence of favorable associations between Mediterranean diet adherence with fertility and gestational weight management. Limited studies suggested associations between higher Mediterranean diet adherence and later time to menarche and fewer vasomotor menopausal symptoms, null associations for polycystic ovary syndrome-like phenotype and pregnancy loss, and positive associations for luteal phase deficiency.
CONCLUSION
Adherence to Mediterranean diet may lower risks of adverse pregnancy outcomes among predominantly White populations. For fertility-related outcomes, available evidence supporting potential beneficial effects is suggestive yet limited. For other reproductive outcomes across the lifespan, data remains sparse.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Child; Adolescent; Young Adult; Polycystic Ovary Syndrome; Diet, Mediterranean; Premature Birth; Reproductive Health; Longevity; Case-Control Studies; Prospective Studies
PubMed: 37506751
DOI: 10.1016/j.ajog.2023.05.030 -
Frontiers in Neuroendocrinology Oct 2023Mucosal secretory immunoglobulin A (s-IgA) has been recognized as a key component of human first line defense against infection. However, its reactivity to psychosocial...
Mucosal secretory immunoglobulin A (s-IgA) has been recognized as a key component of human first line defense against infection. However, its reactivity to psychosocial stressors is poorly understood. This systematic review aimed to explore whether s-IgA levels changed after psychosocial stress in subjects under the age of 18. Fifteen articles were included. s-IgA basal levels are increased in children older than 9 years old exposed to stress. Furthermore, s-IgA seems to follow a circadian rhythm, which is altered under stress conditions. Finally, the collective evidence suggests that salivary s-IgA rapidly increases under acute stress after puberty. Overall, our review indicates that s-IgA could be considered a potential psychosocial stress biomarker of interest for pediatric and child-juvenile psychiatric population. Further studies are needed to validate the role of s-IgA circadian rhythm and basal levels as psychosocial stress biomarkers and disentangle the role of age and type of stressor.
Topics: Humans; Child; Immunoglobulin A, Secretory; Saliva; Stress, Psychological; Biomarkers; Circadian Rhythm
PubMed: 37479062
DOI: 10.1016/j.yfrne.2023.101083 -
Early Human Development Aug 2023A secular trend towards earlier age at menarche has been reported, but the trend in breast development is less clear. We reviewed the evidence on the relationship... (Review)
Review
BACKGROUND
A secular trend towards earlier age at menarche has been reported, but the trend in breast development is less clear. We reviewed the evidence on the relationship between in utero and early life events and breast onset/development.
METHODS
Eligible studies were identified in PubMed and Embase databases. We selected studies in which female human exposure during fetal or the first years of life was measured or estimated, and associations with breast onset or development were evaluated.
RESULTS
Of the 49 cohort studies and 5 cross-sectional studies identified, 43 provided sufficient data to assess associations. High maternal weight, primiparity, and early weight gain, were related to an increased risk of early breast onset/development in most of the studies that analysed these associations, whereas late breast onset/development was associated with preterm birth. Results were inconsistent for smoking in pregnancy, maternal hypertensive disorders, breastfeeding, diabetes, and small for gestational age. No association emerged for maternal age at delivery, alcohol drinking, and selected drug use during pregnancy, and low birth weight.
CONCLUSIONS
The results of this review show that high maternal weight, primiparity and early weight gain were associated with an increased risk of early breast onset/development. Late breast onset/development was associated with preterm birth. Breast development is a key physical marker of puberty onset, and early puberty development is linked to consequences that can reverberate throughout life. Answering the questions about the interconnections between pre/postnatal environmental exposures and their impact on puberty, represents an important area of multidisciplinary research.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Premature Birth; Cross-Sectional Studies; Prenatal Care; Maternal Age; Weight Gain
PubMed: 37421688
DOI: 10.1016/j.earlhumdev.2023.105816 -
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 -
PloS One 2023We performed a systematic review and meta-analysis on the incidence of secondary tethered spinal cord (TSC) between prenatal and postnatal closure in patients with MMC.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
We performed a systematic review and meta-analysis on the incidence of secondary tethered spinal cord (TSC) between prenatal and postnatal closure in patients with MMC. The objectives was to understand the incidence of secondary TSC after prenatal surgery for MMC compared to postnatal surgery for MMC.
MATERIAL AND METHODS
On May 4, 2023, a systematic search was conducted in Medline, Embase, and the Cochrane Library to gather relevant data. Primary studies focusing on repair type, lesion level, and TSC were included, while non-English or non-Dutch reports, case reports, conference abstracts, editorials, letters, comments, and animal studies were excluded. Two reviewers assessed the included studies for bias risk, following PRISMA guidelines. TSC frequency in MMC closure types was determined, and the relationship between TSC occurrence and closure technique was analyzed using relative risk and Fisher's exact test. Subgroup analysis revealed relative risk differences based on study designs and follow-up periods. A total of ten studies, involving 2,724 patients, were assessed. Among them, 2,293 patients underwent postnatal closure, while 431 received prenatal closure for the MMC defect. In the prenatal closure group, TSC occurred in 21.6% (n = 93), compared to 18.8% (n = 432) in the postnatal closure group. The relative risk (RR) of TSC in patients with prenatal MMC closure versus postnatal MMC closure was 1.145 (95%CI 0.939 to 1.398). Fisher's exact test indicated a statistically non-significant association (p = 0.106) between TSC and closure technique. When considering only RCT and controlled cohort studies, the overall RR for TSC was 1.308 (95%CI 1.007 to 1.698) with a non-significant association (p = .053). For studies focusing on children up until early puberty (maximum 12 years follow-up), the RR for tethering was 1.104 (95%CI 0.876 to 1.391), with a non-significant association (p = 0.409).
CONCLUSION AND DISCUSSION
This review found no significant increase in relative risk of TSC between prenatal and postnatal closure in MMC patients, but a trend of increased TSC in the prenatal group. More long-term data on TSC after fetal closure is needed for better counseling and outcomes in MMC.
Topics: Humans; Female; Pregnancy; Meningomyelocele; Fetus; Neurosurgical Procedures; Incidence; Spinal Cord
PubMed: 37379312
DOI: 10.1371/journal.pone.0287175 -
Annales D'endocrinologie Feb 2024Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of...
BACKGROUND
Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of genetically proven 46,XX aromatase deficiency patients to evaluate hormonal parameters.
METHODS
Retrospective review of case records, collating phenotypic and genotypic data and molecular modeling. Systematic review of 46,XX aromatase deficiency, analyzing data on gonadotropins, estrogen and androgens.
RESULTS
In the seven patients from our center, presentation was frequent in childhood or adolescence (4/7: delayed puberty or hyperandrogenism), with maternal virilization (4/7), predominance of Prader III/IV (5/7), and initial rearing as females (6/7). Three patients had hypoplastic ovaries. One patient had spontaneous regular menses. We report three novel (p.Arg115Pro, p.Arg192Pro, and c.145+1_145+4delins) and two recurrent variants (p.Val370Met, and c.145+1_145+4delins) in western and northern India, respectively. On systematic review (n=43), gonadotropins were elevated (FSH>LH) across ages (except preterm infants), androgens were elevated in about one-third of cases during childhood and puberty, and estradiol was lower than in controls in mini-puberty and puberty. Spontaneous thelarche and streak ovaries were significantly more frequent in patients with non-truncating and truncating variants, respectively.
CONCLUSION
We report uncommon presentations with possible founder variants, and highlight hormonal parameters across ages. Serum FSH levels were elevated except in preterms, and can be used as a diagnostic marker.
Topics: Male; Infant; Female; Adolescent; Humans; Infant, Newborn; Infant, Premature; Gynecomastia; Androgens; Follicle Stimulating Hormone; Gonadotropins; Aromatase; Infertility, Male; Metabolism, Inborn Errors; 46, XX Disorders of Sex Development
PubMed: 37348676
DOI: 10.1016/j.ando.2023.05.010 -
Ecotoxicology and Environmental Safety Jun 2023This is the first pilot meta-analysis on the association of prenatal phthalate exposure with childhood cardiometabolic risks. A systematic literature search was... (Review)
Review
The associations between prenatal phthalate exposure and childhood glycolipid metabolism and blood pressure: An updated systematic review and a pilot meta-analysis of prospective cohort studies.
This is the first pilot meta-analysis on the association of prenatal phthalate exposure with childhood cardiometabolic risks. A systematic literature search was performed in MEDLINE, Web of Science and CNKI (Chinese National Knowledge Infrastructure) until June 5, 2023. A total of seven studies with 5746 children (2646 girls and 3100 boys) were finally included. Four, three and two studies investigated the effects of maternal phthalate exposure on childhood blood pressure (BP), blood lipids and blood glucose profiles, respectively. The pilot meta-analysis suggested that di-2-ethylhexyl phthalate (DEHP) metabolite exposure was associated with a decrease in childhood z-systolic BP (SBP, β = -0.169, 95% CI = -0.338-0.001). Furthermore, the pooled results showed negative relationships of prenatal ∑DEHP exposure with z-SBP (β = -0.109, 95% CI = -0.163 to -0.055) and z-diastolic BP (DBP, β = -0.126, 95% CI = -0.182 to -0.069) in girls. In addition, MEP exposure was associated with z-SBP in girls (β = -0.227, 95% CI = -0.387 to -0.066). The pooled result showed a positive relationship between prenatal ∑DEHP exposure and triglycerides (β = 0.103, 95% CI = 0.028-0.178). The overall results revealed that exposure to ∑DEHP throughout gestation was associated with a decrease in insulin (β = -0.074, 95% CI = -0.144 to -0.004) and glucose (β = -0.129, 95% CI = -0.199 to -0.058) in boys. Interestingly, there was an inverse relationship of prenatal mono- 3 -carboxypropyl phthalate (MCPP) exposure with glucose in pubertal boys (β = -3.749, 95% CIs = -6.758 to -0.741) but not found in postpubertal children. In conclusion, prenatal phthalate exposure interfered with cardiovascular risk in children with gender-specific differences and was influenced by puberty. Overall, prenatal ∑DEHP was negatively associated with systolic blood pressure in girls and with insulin and glucose in boys but increased the level of triglycerides.
PubMed: 37348219
DOI: 10.1016/j.ecoenv.2023.115157 -
Journal of Pediatric and Adolescent... Aug 2023Menstrual dysfunction can impact both the physical and emotional health of young people. Multiple chronic diseases have been associated with menstrual dysfunction in... (Review)
Review
STUDY OBJECTIVE
Menstrual dysfunction can impact both the physical and emotional health of young people. Multiple chronic diseases have been associated with menstrual dysfunction in adults; however, there is little research in adolescents, despite nonadherence and suboptimal illness control in this group. We aimed to identify the impact of chronic illness on the age of menarche and the menstrual cycle in adolescents.
METHODS
Studies were extracted of female adolescents aged 10-19 who had a chronic physical illness. Data included outcomes on age of menarche and/or menstrual cycle quality. Exclusion criteria aimed to exclude diseases where menstrual dysfunction was a known part of the disease pathophysiology (ie, polycystic ovarian syndrome) or in which medications were used that directly impacted gonadal function. A literature search (to January 2022) was performed on the EMBASE, PubMed, and Cochrane library databases. Two widely used modified quality analysis tools were used.
RESULTS
Our initial search netted 1451 articles, of which 95 full texts were examined and 43 met the inclusion criteria. Twenty-seven papers focused on type 1 diabetes (T1D), with 8 papers examining adolescents with cystic fibrosis and the remaining studying inflammatory bowel disease, juvenile idiopathic arthritis, coeliac disease, and chronic renal disease. Metanalysis of 933 patients with T1D vs 5244 controls demonstrated a significantly later age of menarche in T1D (by 0.42 years; P ≤ .00001). There was also a significant association between higher HbA1c and insulin dose (IU/kg) and later age of menarche. Eighteen papers reviewed other aspects of menstruation, including dysmenorrhea, oligomenorrhoea, amenorrhea, and ovulatory function, with variable findings.
CONCLUSION
Most studies were small and in single populations. Despite this, there was evidence of delayed menarche and some evidence of irregular menses in those with cystic fibrosis and T1D. Further structured studies are needed to evaluate menstrual dysfunction in adolescents and how it relates to their chronic illness.
Topics: Adult; Female; Humans; Adolescent; Menstruation; Diabetes Mellitus, Type 1; Cystic Fibrosis; Menstruation Disturbances; Menarche; Menstrual Cycle; Chronic Disease
PubMed: 37192680
DOI: 10.1016/j.jpag.2023.05.005