Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future

The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG) axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH). Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are genetic disorders that are rooted in a GnRH deficiency but often accompanied by a variety of non-reproductive phenotypes such as the loss of the sense of smell and defects of the skeleton, eye, ear, kidney, and heart. Recent progress in DNA sequencing technology has produced a wealth of information regarding the genetic makeup of CHH and KS patients and revealed the resilient yet complex nature of the human reproductive neuroendocrine system. Further research on the molecular basis of the disease and the diverse signal pathways involved will aid in improving the diagnosis, treatment, and management of CHH and KS patients as well as in developing more precise genetic screening and counseling regime

Anogenital distance as a marker of androgen exposure in humans.

Abnormal foetal testis development has been proposed to underlie common disorders of the male reproductive system such as cryptorchidism, hypospadias, reduced semen quality and testicular germ cell tumour, which are regarded as components of a 'testicular dysgenesis syndrome'. The increasing trends and geographical variation in their incidence have been suggested to result from in utero exposure to environmental chemicals acting as endocrine disruptors. In rodents, the anogenital distance (AGD), measured from the anus to the base of genital tubercle, is a sensitive biomarker of androgen exposure during a critical embryonic window of testis development. In humans, several epidemiological studies have shown alterations in AGD associated with prenatal exposure to several chemicals with potential endocrine disrupting activity. However, the link between AGD and androgen exposure in humans is not well-defined. This review focuses on the current evidence for such a relationship. As in rodents, a clear gender difference is detected during foetal development of the AGD in humans which is maintained thereafter. Reduced AGD in association with clinically relevant outcomes of potential environmental exposures, such as cryptorchidism or hypospadias, is in keeping with AGD as a marker of foetal testicular function. Furthermore, AGD may reflect variations in prenatal androgen exposure in healthy children as shorter AGD at birth is associated with reduced masculine play behaviour in preschool boys. Several studies provide evidence linking shorter AGD with lower fertility, semen quality and testosterone levels in selected groups of adults attending andrology clinics. Overall, the observational data in humans are consistent with experimental studies in animals and support the use of AGD as a biomarker of foetal androgen exposure. Future studies evaluating AGD in relation to reproductive hormones in both infants and adults, and to gene polymorphisms, will help to further delineate the effect of prenatal and postnatal androgen exposures on AGD.The CBGS studies referred to in this review were supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), the Newlife Foundation, the Mothercare Foundation, the Evelyn Trust and the NIHR Cambridge Biomedical Research Centre.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/andr.1215

Evaluation of vitamin D status and its correlation with gonadal function in children at mini-puberty

WOS: 000453904100014PubMed ID: 30229999Context The effects of Vitamin D on reproductive function in adults have gained interest. Studies have demonstrated some associations. Hypothalamic-pituitary-gonadal axis is activated during the first 6 months of life, called as mini-puberty. This HPG activation is important for future gonadal function. There are no data regarding the association of gonadal hormones and 25(OH)D levels at mini-puberty. Demonstration of any association would form the basis for studies that will search for the effects of 25(OH)D on gonadal hormones at mini-puberty. Objective To characterize the associations between 25(OH)D levels and gonadal hormones at mini-puberty. Design Cross-sectional cohort analysis. Patient(s) or other participant(s) A total of 180 (94 boys and 86 girls) healthy appropriate-for-gestational-age neonates were included. Main outcome measure(s) 25(OH)D, LH, FSH, total testosterone, oestradiol, AMH and inhibin B levels were measured at postnatal 30-45 days. All infants were divided into three groups including vitamin D deficiency (20 ng/mL). Correlations between vitamin D status and reproductive hormones were analysed. Result(s) Total testosterone level was higher (mean: 0.52 +/- 0.32 vs 0.26 +/- 0.2 ng/mL; P: 0.008) and inhibin B was lower in 25(OH)D deficient than sufficient girls (mean: 21.2 +/- 15.71 vs 53.25 +/- 47.25 pg/mL; P: 0.021). Conclusion(s) A modest effect of 25(OH)D was identified on total testosterone and inhibin B in girls at mini-puberty. The 25(OH)D may have an effect on gonadal function during early life. Randomized controlled trials could clarify the importance of vitamin D on gonadal hormones at mini-puberty

Society for Endocrinology UK guidance on the evaluation of suspected disorders of sexual development: emphasizing the opportunity to predict adolescent pubertal failure through a neonatal diagnosis of absent minipuberty.

The recent Society for Endocrinology (SFE) UK Guidance on the Initial Evaluation of an Infant or an Adolescent with a Suspected Disorder of Sex Development (DSD) provides invaluable advice for clinicians treating affected patients (Ahmed, et al., 2016). Such reports are key to synthesizing evidence, sharing expert opinion and emphasizing the importance of supporting patients and families with rare disorders within the context of a multidisciplinary approach. This article is protected by copyright. All rights reserved

Transient Postnatal Gonadal Activation and Growth Velocity in Infancy

Kuopio University Hospital, the Pediatric Research Foundation, the Finnish National Graduate School of Clinical Investigation, the Emil Aaltonen Foundation, the Jalmari and Rauha Ahokas Foundation, the Sigrid Jusélius Foundation, the Academy of Finland, and the Finnish Medical Foundation