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The Journal of Clinical Endocrinology... Oct 2023Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for activating and maintaining the function of the hypothalamic-pituitary-gonadal axis, which... (Review)
Review
Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for activating and maintaining the function of the hypothalamic-pituitary-gonadal axis, which controls the onset of puberty and fertility. Two recent studies suggest that, in addition to controlling reproduction, the neurons in the brain that produce GnRH are also involved in the control of postnatal brain maturation, odor discrimination, and adult cognition. This review will summarize the development and establishment of the GnRH system, with particular attention to the importance of its first postnatal activation, a phenomenon known as minipuberty, for later reproductive and nonreproductive functions. In addition, we will discuss the beneficial effects of restoring physiological (ie, pulsatile) GnRH levels on olfactory and cognitive alterations in preclinical Down syndrome and Alzheimer disease models, as well as the potential risks associated with long-term continuous (ie, nonphysiological) GnRH administration in certain disorders. Finally, this review addresses the intriguing possibility that pulsatile GnRH therapy may hold therapeutic potential for the management of some neurodevelopmental cognitive disorders and pathological aging in elderly people.
Topics: Adult; Aged; Humans; Cognition; Fertility; Gonadotropin-Releasing Hormone; Puberty; Reproduction
PubMed: 37261390
DOI: 10.1210/clinem/dgad319 -
Frontiers in Endocrinology 2023
Topics: Sexual Maturation; Humans; Puberty
PubMed: 37560304
DOI: 10.3389/fendo.2023.1258656 -
Frontiers in Endocrinology 2024Cryptorchidism is the condition in which one or both testes have not descended adequately into the scrotum. The congenital form of cryptorchidism is one of the most... (Review)
Review
Cryptorchidism is the condition in which one or both testes have not descended adequately into the scrotum. The congenital form of cryptorchidism is one of the most prevalent urogenital anomalies in male newborns. In the acquired form of cryptorchidism, the testis that was previously descended normally is no longer located in the scrotum. Cryptorchidism is associated with an increased risk of infertility and testicular germ cell tumors. However, data on pubertal progression are less well-established because of the limited number of studies. Here, we aim to review the currently available data on pubertal development in boys with a history of non-syndromic cryptorchidism-both congenital and acquired cryptorchidism. The review is focused on the timing of puberty, physical changes, testicular growth, and endocrine development during puberty. The available evidence demonstrated that the timing of the onset of puberty in boys with a history of congenital cryptorchidism does not differ from that of non-cryptorchid boys. Hypothalamic-pituitary-gonadal hormone measurements showed an impaired function or fewer Sertoli cells and/or germ cells among boys with a history of cryptorchidism, particularly with a history of bilateral cryptorchidism treated with orchiopexy. Leydig cell function is generally not affected in boys with a history of cryptorchidism. Data on pubertal development among boys with acquired cryptorchidism are lacking; therefore, more research is needed to investigate pubertal progression among such boys.
Topics: Infant, Newborn; Humans; Male; Cryptorchidism; Testicular Neoplasms; Leydig Cells; Puberty
PubMed: 38532895
DOI: 10.3389/fendo.2024.1347435 -
Journal of Pediatric and Adolescent... Oct 2023Prepubertal bleeding is a common presentation in the pediatric office and can be distressing for patients and families. A comprehensive approach to diagnosis and... (Review)
Review
BACKGROUND
Prepubertal bleeding is a common presentation in the pediatric office and can be distressing for patients and families. A comprehensive approach to diagnosis and management allows clinicians to identify patients at risk for worrisome pathology and arrange timely care.
OBJECTIVE
We aimed to review the key features of clinical history, physical exam, and diagnostic workup of a child presenting with prepubertal bleeding. We reviewed potential pathologies requiring urgent investigations and management, such as precocious puberty and malignancy, as well as more common etiologies, including foreign bodies and vulvovaginitis.
CONCLUSION
Clinicians should approach each patient with the goal of excluding diagnoses that require urgent interventions. A thoughtful clinical history and physical exam can inform appropriate investigations to optimize patient care.
Topics: Female; Child; Humans; Uterine Hemorrhage; Vulvovaginitis; Foreign Bodies; Physical Examination; Puberty, Precocious
PubMed: 37301426
DOI: 10.1016/j.jpag.2023.06.002 -
Endocrinology and Metabolism Clinics of... Jun 2024Delayed puberty is defined as absent testicular enlargement in boys or breast development in girls at an age that is 2 to 2.5 SDS later than the mean age at which these... (Review)
Review
Delayed puberty is defined as absent testicular enlargement in boys or breast development in girls at an age that is 2 to 2.5 SDS later than the mean age at which these events occur in the population (traditionally, 14 years in boys and 13 years in girls). One cause of delayed/absent puberty is hypogonadotropic hypogonadism (HH), which refers to inadequate hypothalamic/pituitary function leading to deficient production of sex steroids in males and females. Individuals with HH typically have normal gonads, and thus HH differs from hypergonadotropic hypogonadism, which is associated with primary gonadal insufficiency.
Topics: Humans; Hypogonadism; Male; Female; Adolescent; Puberty, Delayed
PubMed: 38677870
DOI: 10.1016/j.ecl.2024.01.008 -
BMC Medicine Sep 2023Few studies have investigated associations between adiposity and reproductive factors using causal methods, both of which have a number of consequences on women's...
BACKGROUND
Few studies have investigated associations between adiposity and reproductive factors using causal methods, both of which have a number of consequences on women's health. Here we assess whether adiposity at different points in the lifecourse affects reproductive factors differently and independently, and the plausibility of the impact of reproductive factors on adiposity.
METHODS
We used genetic data from UK Biobank (273,238 women) and other consortia (EGG, GIANT, ReproGen and SSGAC) for eight reproductive factors: age at menarche, age at menopause, age at first birth, age at last birth, number of births, being parous, age first had sexual intercourse and lifetime number of sexual partners, and two adiposity traits: childhood and adulthood body size. We applied multivariable Mendelian randomization to account for genetic correlation and to estimate the causal effects of childhood and adulthood adiposity, independently of each other, on reproductive factors. Additionally, we estimated the effects of reproductive factors, independently of other relevant reproductive factors, on adulthood adiposity.
RESULTS
We found a higher childhood body size leads to an earlier age at menarche, and an earlier age at menarche leads to a higher adulthood body size. Furthermore, we find contrasting and independent effects of childhood and adulthood body size on age at first birth (beta 0.22 SD (95% confidence interval: 0.14, 0.31) vs - 2.49 (- 2.93, - 2.06) per 1 SD increase), age at last birth (0.13 (0.06,0.21) vs - 1.86 (- 2.23, - 1.48) per 1 SD increase), age at menopause (0.17 (0.09, 0.25) vs - 0.99 (- 1.39, - 0.59) per 1 SD increase), and likelihood of having children (Odds ratio 0.97 (0.95, 1.00) vs 1.20 (1.06, 1.37) per 1 SD increase).
CONCLUSIONS
Our findings demonstrate the importance of considering a lifecourse approach when investigating the inter-relationships between adiposity measures and reproductive events, as well as the use of 'age specific' genetic instruments when evaluating lifecourse hypotheses in a Mendelian randomization framework.
Topics: Female; Humans; Adiposity; Menarche; Mendelian Randomization Analysis; Menopause; Obesity
PubMed: 37697382
DOI: 10.1186/s12916-023-03051-x -
CNS Neuroscience & Therapeutics Oct 2023The relationship between the age at menarche (AAM) and the risk of intracerebral hemorrhage (ICH) and ischemic stroke (IS) is still up for debate. The purpose of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between the age at menarche (AAM) and the risk of intracerebral hemorrhage (ICH) and ischemic stroke (IS) is still up for debate. The purpose of this study was to investigate potential causal connections between them.
METHODS
Genome-wide association analysis (GWAS) of AAM conducted by the MRC-IEU consortium was utilized for association analyses of ICH and IS by two-sample Mendelian randomization (MR) study. AAM data of the within-family GWAS consortium were used as replication phase data to verify the causal relationship between each other. Inverse variance weighting (IVW) method was the primary method used in this MR study. For additional proof, the weighted median estimation, MR-Egger regression, MR-PRESSO test, and MR-Robust Adjusted Profile Score evaluation were performed. The Cochran's Q test and the MR-PRESSO global test were used, respectively, to examine the sensitivity and pleiotropy. Random effects meta-analysis was utilized to analyze the causal data from the two consortiums to further explore the causality between AAM and ICH, IS.
RESULTS
We found that the AAM was causally linked with the risk of ICH (OR = 0.48, 95% CI: 0.28-0.80, p = 0.006). On the contrary, the causal effect from AAM to IS (OR = 0.98, 95% CI: 0.91-1.06, p = 0.64) has not been confirmed. For all subtypes of ICH, we found that nonlobar intracerebral hemorrhage (NLICH, OR = 0.41, 95% CI: 0.23-0.75, p = 0.004) but not lobar intracerebral hemorrhage (LICH, OR = 0.65, 95% CI: 0.34-1.24, p = 0.19) was associated with AAM without surprise. Similarly, we used the within-family GWAS consortium data to explore causality and found that AAM may reduce the risk of ICH (OR = 0.78, 95% CI: 0.72-0.86, p = 9.5 × 10 ) and NLICH (OR = 0.68, 95% CI: 0.61-0.75, p = 3.4 × 10 ) by IVW methods, but is not related to IS (OR = 0.97, 95% CI: 0.93-1.02, p = 0.26). These findings are further supported by the meta-analysis. Both Cochran's Q test and the MR-PRESSO global test failed to detect the presence of sensitivity.
CONCLUSION
AAM and ICH, particularly NLICH, are causally related, but not LICH, IS, or its subtypes in European population.
Topics: Female; Humans; Ischemic Stroke; Genome-Wide Association Study; Menarche; Mendelian Randomization Analysis; Cerebral Hemorrhage
PubMed: 37170723
DOI: 10.1111/cns.14245 -
International Journal of Gynaecology... Sep 2023The authors aimed to use a large two-sample Mendelian randomization (MR) study to reveal the causality between age at menarche (AAM) and polycystic ovary syndrome (PCOS)...
OBJECTIVE
The authors aimed to use a large two-sample Mendelian randomization (MR) study to reveal the causality between age at menarche (AAM) and polycystic ovary syndrome (PCOS) incidence.
METHODS
The authors collected summary statistics from the hitherto largest genome-wide association studies conducted in AAM and PCOS in the same ancestry. MR with inverse variance weighting was conducted as the main analysis method, while weighted median and MR-Egger regression were used for comprehensive analysis. As for pleiotropy detection, inverse variance weighting, MR-Egger regression, Mendelian Randomization Pleiotropy Residual Sum and Outlier, as well as leave-one-out analysis were used to detect pleiotropy. Risk factor analysis was conducted to investigate the underlying mechanisms linking AAM to PCOS.
RESULTS
Each standard deviation increment in AAM was associated with a significantly lower incidence of PCOS (odds ratio, 0.86 [95% confidence interval, 0.75-0.98]). After adjustment in horizontal pleiotropy by eliminating four outliers, this pathogenic association was still statistically detected. All pleiotropy indexes were without statistical differences, which suggested the conclusions were robust. It showed the causal association between later AAM and lower body mass index, lower fasting insulin level and insulin resistance.
CONCLUSION
Our MR analysis verified that a slightly later onset age (15 to 18 years) at menarche could reduce the risk of PCOS. A more comprehensive investigation in a prospective setting is strongly advised.
Topics: Female; Humans; Adolescent; Polycystic Ovary Syndrome; Menarche; Genome-Wide Association Study; Mendelian Randomization Analysis; Prospective Studies
PubMed: 37128830
DOI: 10.1002/ijgo.14820 -
Children (Basel, Switzerland) Oct 2023Nutrients have an enormous impact on many hormonal systems and aspects of health, and nutrition status is a crucial regulator of growth and pubertal development in... (Review)
Review
Nutrients have an enormous impact on many hormonal systems and aspects of health, and nutrition status is a crucial regulator of growth and pubertal development in children and adolescents. In this narrative review, we explore the connection between these feeding methods and the timing of puberty to provide a clearer understanding of how infant nutrition might contribute to the early development of puberty. Puberty is a key stage in the transition from childhood to adulthood and the timing of puberty represents a significant biological milestone of growth. Breast milk seems to have a pivotal role in puberty onset, mainly due to its dynamism, which shape indirectly the gut microbiota in early life, besides direct exposure of the baby to the milk microbiota through gut-breast axis. Concerning breast and formula milk and their effects on the onset of puberty, a protective role of the former occurs. As for the potential harmful effects of soy-based formulas and the isoflavones that they contain, the studies reported demonstrate conflicting opinions, underlining the need for further research on this topic. A healthy and well-nourished diet from the earliest stages of life has significant preventive potential for overall well-being, reducing the risk of many health problems later in life.
PubMed: 37892349
DOI: 10.3390/children10101686