Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty

Background： Delayed puberty can result either from constitutional delay of growth and puberty （CDP） or idiopathic hypogonadotropic hypogonadism （IHH）. Gonadotropin-releasing hormone （GnRH） stimulation test has been generally accepted as a current method for diagnosing delayed puberty. The objective of this research was to assess the cut-offvalues and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females. Methods： A study of 91 IHH, 27 CDP patients, 6 prepubertal children, and 20 pubertal adults was undertaken. Blood samples were obtained at 0, 30, 60, and 120 rain after GnRH administration and the levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） were rneast, red. For each paralneter, the sensitivities and specificities were estimated, and the receiver operating characteristic （ROC） curves were constructed. Resulis： The ROC curves indicated that a serunl basal LH 〈0.6 IU/L or peak LH 〈9.74 IU/L resulted in moderate sensitivity （73.8% or 80.0%） and specificity （90.9% or 86.4%） in the diagnosis of HH in males. Serum basal LH 〈0.85 IU/L or basal FSH 〈2.43 IU/L resulted in moderate sensitivity （80.0% or 100.0%） and specificity （75.0% or 50.0%） in the diagnosis of HH in females. Conclusions： Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males, but unnecessary in females. The most useful predictor is serum basal or peak LH to differentiate these two disorders in males, but serum basal LH or FSH in females.

A classification of genes involved in normal and delayed male puberty

Puberty is a pivotal biological process that completes sexual maturation to achieve full reproductive capability.It is a major transformational period of life,whose timing is strongly affected by genetic makeup of the individual,along with various internal and external factors.Although the exact mechanism for initiation of the cascade of molecular events that culminate in puberty is not yet known,the process of pubertal onset involves interaction of numerous complex signaling pathways of hypothalamopituitary-testicular(HPT)axis.We developed a classification of the mechanisms involved in male puberty that allowed placing many genes into physiological context.These include(i)hypothalamic development during embryogenesis,(ii)synaptogenesis where gonadotropin releasing hormone(GnRH)neurons form neuronal connections with suprahypothalamic neurons,(iii)maintenance of neuron homeostasis,(iv)regulation of synthesis and secretion of GnRH,(v)appropriate receptors/proteins on neurons governing GnRH production and release,(vi)signaling molecules activated by the receptors,(vii)the synthesis and release of GnRH,(viii)the production and release of gonadotropins,(ix)testicular development,(x)synthesis and release of steroid hormones from testes,and(xi)the action of steroid hormones in downstream effector tissues.Defects in components of this system during embryonic development,childhood/adolescence,or adulthood may disrupt/nullify puberty,leading to long-term male infertility and/or hypogonadism.This review provides a list of 598 genes involved in the development of HPT axis and classified according to this schema.Furthermore,this review identifies a subset of 75 genes for which genetic mutations are reported to delay or disrupt male puberty.

Comparing Women and Men’s Experiences with Kallmann Syndrome

Topic: Kallmann syndrome (KS) is a congenital olfacto-genital disease. Affected persons show an absence of physical pubertal development, and their sense of smell is reduced or absent (anosmia). The prevalence is 1:40,000 in women and 1:8000 to 1:10,000 in men. Development of gender identity corresponds to the assigned gender at birth. The cause of KS is a genetic defect. To date, only a few systematic investigations have delved into the psychological disstress and consequences of the somatic characteristics of KS. In order for affected persons to be appropriately informed, well-founded research results are necessary. The focus of the present study aims at examining the similarities and differences between the psychological disstress and consequences women and men experience through the development, on the one hand, and through its medical treatment on the other. The present text complements current findings on the psychological consequences of KS in men [1] and women, respectively [2]. Two questions lie at the center of the comparison: 1) Which similarities and which gender-specific differences are there concerning the perceived burdens? 2) Which coping strategies have been developed in dealing with the burdens and consequences caused by KS in the affected women and men? Which similarities and which gender-specific differences are there with respect to these coping strategies? Methodology: The survey has been carried out by means of topically focused narrative interviews of 16 men and 5 women. Based on the qualitative content analysis according to Mayring [3], categories have been generated and evaluated on the basis of the interview material. The results of the male and female samples have been contrasted and analyzed in gender-specific relevant key subjects [1,2]. Results: The comparison shows that the burdens women and men experience through KS go beyond the somato-medical problems, and that the psychosocial consequences are a heavy burden for the members of both groups. Men bear a heavier burden through insecurities and shame about the absence of virilization and subsequently suffer more from bullying and marginalization experiences. They also perceive mood changes more frequently and as more burdensome through the course of hormone treatment. Women also develop shame due to the absence of female body development;they do, however, perceive this as less burdensome than do men. They suffer particularly from a loss of libido before and also during hormone treatment. Differences occur concerning the gender-specific hormone treatment and its effects on mood and libido. Wellfounded statements relating to this do, however, require further-reaching studies. In women, KS is frequently misdiagnosed as simply estrogen deficiency, which could be an explanation for the differing degree of prevalence. The preferred coping strategies for both sexes include confidential talks with suitable people, such as parents, the partner, friends, or a psychotherapist. Using support from psychotherapists, sex education, and/or sexual therapists is recommended when necessary. Conclusion: Psychotherapeutic/psychological support is recommended for both women and men diagnosed with KS, taking into account the gender-specific differences in dealing with the burdens KS imposes. The focus for both sexes should be on developing and strengthening body image and self-esteem. In medical treatment for both women and men, normal or inconspicuous body development should be emphasized. Particularly in the case of women, sex therapy should be available for support due to loss of libido. For men, therapy should be recommended, so as to strengthen their social capabilities and self-confidence. Additional studies are necessary for examining the effects of hormonal treatment on mood and libido and phenotyp.

Method to assess component contribution to toxicity of complex mixtures： Assessment of puberty acquisition in rats exposed to disinfection byproducts

A method based on regression modeling was developed to discern the contribution of component chemicals to the toxicity of highly complex, environmentally realistic mixtures of disinfection byproducts（DBPs）. Chemical disinfection of drinking water forms DBP mixtures.Because of concerns about possible reproductive and developmental toxicity, a whole mixture（WM） of DBPs produced by chlorination of a water concentrate was administered as drinking water to Sprague–Dawley（S–D） rats in a multigenerational study. Age of puberty acquisition,i.e., preputial separation（PPS） and vaginal opening（VO）, was examined in male and female offspring, respectively. When compared to controls, a slight, but statistically significant delay in puberty acquisition was observed in females but not in males. WM-induced differences in the age at puberty acquisition were compared to those reported in S–D rats administered either a defined mixture（DM） of nine regulated DBPs or individual DBPs. Regression models were developed using individual animal data on age at PPS or VO from the DM study. Puberty acquisition data reported in the WM and individual DBP studies were then compared with the DM models. The delay in puberty acquisition observed in the WM-treated female rats could not be distinguished from delays predicted by the DM regression model, suggesting that the nine regulated DBPs in the DM might account for much of the delay observed in the WM. This method is applicable to mixtures of other types of chemicals and other endpoints.