Sample records for adrenarche

  1. Premature adrenarche: novel lessons from early onset androgen excess.

    Idkowiak, Jan; Lavery, Gareth G; Dhir, Vivek; Barrett, Timothy G; Stewart, Paul M; Krone, Nils; Arlt, Wiebke


    Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

  2. Childhood environment influences adrenarcheal timing among first-generation Bangladeshi migrant girls to the UK.

    Lauren C Houghton

    Full Text Available BACKGROUND: Adrenarche is a key early life event that marks middle childhood at approximately 7 years of age. Earlier work with British-Bangladeshi migrant women suggested that environmental conditions experienced before adrenarche influence adult reproductive function. We therefore investigated whether Bangladeshi children who migrate to the United Kingdom (UK reach adrenarche earlier than non-migrants in Bangladesh or the United Kingdom. METHODS AND FINDINGS: Healthy girls, aged 5-16 years, were recruited from schools in Sylhet, Bangladesh and London, England comprising four groups: Sylhetis (n = 165, first-generation migrants to the United Kingdom (n = 42, second-generation girls (n = 162, and British girls of European origin (n = 50. Anthropometric measurements were collected together with questionnaire data for migration and socioeconomic characteristics. Saliva samples were assayed for dehydroepiandrosterone (DHEAS using enzyme-linked immunosorbent assays. Multiple linear regressions tested for group differences in anthropometric and socioeconomic variables and DHEAS levels. Median ages at adrenarche (DHEAS>400 pg/ml were estimated using Weibull regression models for parametric survival analysis. Hazard ratios for reaching adrenarche earlier and 95% confidence intervals (CI, both unadjusted and adjusted for anthropometric variables, were estimated from the survival analyses. First-generation migrants had a median age at adrenarche (5.3 years that was significantly earlier than Sylheti (7.2, second-generation (7.4, and European (7.1 girls. In univariate analyses, first-generation girls reached adrenarche significantly earlier than Sylhetis [HR (CI: 2.8 (1.4-5.5]. In multivariate models, first generation girls still reached adrenarche earlier than Sylhetis after adjusting for height [HR(CI: 1.9 (0.9-4.1] and weight [HR(CI:1.7 (0.8-3.8], but these results were attenuated. CONCLUSIONS: We suggest that rapid catch-up growth

  3. Adrenarche in nonhuman primates: the evidence for it and the need to redefine it.

    Conley, A J; Bernstein, R M; Nguyen, A D


    Adrenarche is most commonly defined as a prepubertal increase in circulating adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfo-conjugate (DHEAS). This event is thought to have evolved in humans and some great apes but not in Old World monkeys, perhaps to promote brain development. Whether adrenarche represents a shared, derived developmental event in humans and our closest relatives, adrenal androgen secretion (and its regulation) is of considerable clinical interest. Specifically, adrenal androgens play a significant role in the pathophysiology of polycystic ovarian disease and breast and prostate cancers. Understanding the development of androgen secretion by the human adrenal cortex and identifying a suitable model for its study are therefore of central importance for clinical and evolutionary concerns. This review will examine the evidence for adrenarche in nonhuman primates (NHP) and suggest that a broader definition of this developmental event is needed, including morphological, biochemical, and endocrine criteria. Using such a definition, evidence from recent studies suggests that adrenarche evolved in Old World primates but spans a relatively brief period early in development compared with humans and some great apes. This emphasizes the need for frequent longitudinal sampling in evaluating developmental changes in adrenal androgen secretion as well as the tenuous nature of existing evidence of adrenarche in some species among the great apes. Central to an understanding of the regulation of adrenal androgen production in humans is the recognition of the complex nature of adrenarche and the need for more carefully conducted comparative studies and a broader definition in order to promote investigation among NHP in particular.

  4. In the zone: understanding zona reticularis function and its transformation by adrenarche.

    Bird, Ian M


    The human adrenal cortex comprises three distinct zones with unique steroid products, namely the zona glomerulosa, which secretes the mineralocorticoids, the zona fasciculate, which secretes the glucocorticoids and the zona reticularis (ZR), which at adrenarche, begins to produce the so-called adrenal androgens. Of all the adrenal zones, we still understand control of ZR emergence the least, and yet the consequences of such dysregulation can be devastating. Premature adrenarche is a growing problem and the correspondingly inappropriate emergence of ZR function can negatively influence puberty and lead to adult infertility. Our understanding is limited and more needs to be done. The purpose of these three reviews is to provide a survey of where we are in our current understanding of what adrenarche is, and indeed if it is unique to humans at all. Furthermore, these reviews describe what is also known of how the functional ZR emerges during adrenarche and what steroids of physiologic relevance result beyond the widely known DHEA and DHEAS elevated at this time. Such advances in human, primate and indeed stem-cell biology are clearly laying the foundation for new directions in the hunt for the factors involved in the regulation and functional emergence of a ZR at the appropriate time, as well as insight into how they may fail. Given support for these new directions, considerable progress can clearly be made.

  5. Is basal serum 17-OH progesterone a reliable parameter to predict nonclassical congenital adrenal hyperplasia in premature adrenarche?

    Gönç, E Nazli; Ozön, Z Alev; Alikaşifoğlu, Ayfer; Engiz, Ozlem; Bulum, Burcu; Kandemir, Nurgün


    To determine the critical features for the diagnosis of nonclassical 21 hydroxylase deficiency (NC210HD) without performing adrenocorticotropic hormone (ACTH) test, we studied 186 cases with premature adrenarche. Clinical and laboratory features as well as basal 17-hydroxyprogesterone (17-OHP) were analyzed to determine factors important for differentiating NC21OHD. Overall, 6 patients (3.2%) had ACTH-stimulated 17-OHP > 10 ng/ml. A cutoff level of 2 ng/ml for basal 17-OHP was 66.7% sensitive and 78% specific for NC21OHD; however, a cutoff level of 1.55 ng/ml had higher sensitivity (83%) and specificity (70.6%). A cutoff of 1.55 ng/ml would lead to 31% of cases with premature adrenarche having to undergo ACTH test, and only one case would have been missed. That case had a bone age SDS > 2. Three cases out of five with a basal 17-OHP > 5 ng/ml had stimulated 17-OHP bone SDS > 2 in those with lower basal levels as a guide for carrying out an ACTH test may yield better results in the diagnosis of NC21OHD in the premature adrenarche population. A cutoff of 5 ng/ml for basal 17-OHP should not be used for diagnosis of NC21OHD.

  6. LH Dynamics in Overweight Girls with Premature Adrenarche and Slowly Progressive Sexual Precocity

    Rosenfield RobertL


    Full Text Available Background. Excess adiposity and premature adrenarche (PA are risk factors for the development of polycystic ovary syndrome (PCOS. Methods. Girls with slowly progressive precocious breast development, who were overweight and had PA (SPPOPA, 6.2–8.2 years, , overweight PA (6.6–10.8 years, , and overweight premenarcheal controls (OW-PUB, 10.6–12.8 years, underwent hormonal sleep testing and GnRH agonist (GnRHag and ACTH tests. Results. Despite an insignificant sleep-related increase in LH and prepubertal baseline hormone levels, SPPOPA peak LH and estradiol responses to GnRHag were intermediate between those of PA and OW-PUB, the LH being significantly different from both. Conclusions. GnRHag tests indicate that SPPOPA is a slowly progressive form of true puberty with blunted LH dynamics. These results argue against the prepubertal hyperandrogenism of excess adiposity or PA enhancing LH secretion or causing ovarian hyperandrogenism prior to menarche. Excess adiposity may contribute to both the early onset and slow progression of puberty.

  7. [The relationship between metabolic disorders and small for gestational age with idiopathic premature adrenarche].

    Mejorado Molano, Francisco Javier; Andrés Zallo, Laura; Fornos Rodríguez, Marta; Pérez Segura, Pilar; Gavela Pérez, Teresa; Sanz Calvo, María Luisa; Soriano Guillén, Leandro


    There is still controversy on the relationship between idiopathic premature adrenarche (IPA) and a history of small for gestational age, as well as the concomitant presence of obesity and other metabolic disturbances. An attempt is made to study these potential associations in a cohort of girls with IPA from our hospital. A descriptive cross-sectional study was conducted that included girls with a diagnosis of IPA from the Paediatric Department of the Fundación Jiménez Díaz (Madrid, Spain) between January 2007 and May 2015. A record was made of family and personal history with perinatal data, as well as anthropometric data and biochemical values at the time of diagnosis. Out of a total of 76 girls with IPA, 2.7% had a history of small for gestational age. When body mass index was analysed according to modified criteria of WHO 2007/Cole 2000, 11.8% were overweight, and 11.8% were obese at diagnosis. Using the criteria set by the Spanish Ministry of Health, 6.6% were overweight and 18.4% obese, with 21.2% of the girls being insulin resistance, and 13.95% having dyslipidaemia. None of them had hypertension. From a comparative analysis between normal and overweight and obesity IPA girls, the latter had significantly higher levels of triglycerides and insulin, a higher HOMA index, and lower levels of HDL cholesterol. IPA girls included in the study do not have a higher prevalence of small for gestational age compared to the general population. Prevalence of overweight and obesity in girls with IPA is not higher than the prevalence in the normal population. Copyright © 2016. Publicado por Elsevier España, S.L.U.

  8. Adrenal androgen hyperresponsiveness to adrenocorticotropin in women with acne and/or hirsutism: adrenal enzyme defects and exaggerated adrenarche.

    Lucky, A W; Rosenfield, R L; McGuire, J; Rudy, S; Helke, J


    To determine the adrenal contribution to elevated plasma androgens in 31 young hyperandrogenemic women with acne and/or hirsutism, we compared their responses to ACTH with those of 14 normal women. Each subject was given a low dose (10 micrograms/m2) of synthetic ACTH-(1-24) (Cortrosyn) after administration of 1.5 mg dexamethasone the night before the test. Thirty and 60 min responses of plasma 17 alpha-hydroxypregnenolone (17-Preg), 17 alpha-hydroxyprogesterone, (17-prog), dehydroepiandrosterone (DHEA), androstenedione, 11-deoxycortisol, and cortisol were measured. Eighteen (58%) patients had increased responses of at least one 17-ketosteroid or adrenal androgen precursor. All patients had cortisol responses within the range of those of the 14 normal subjects. Nine patients (29%) had evidence of steroid biosynthetic enzyme deficiencies, either mild congenital adrenal hyperplasia or the heterozygote state; after ACTH, 4 of these patients had elevated 17-prog in the range of values in heterozygote carriers of 21-hydroxylase deficiency, 2 had elevated levels of 11-deoxycortisol compatible with 11 beta-hydroxylase deficiency, and 3 had elevated levels of 17-Preg and DHEA, suggestive of 3 beta-hydroxysteroid dehydrogenase deficiency. Another 9 subjects (29%) had 17-ketosteroid (DHEA and/or androstenedione) hyperresponsiveness to ACTH with associated elevated 17-Preg responses. As a group, their patterns suggested relatively deficient 3 beta-hydroxysteroid dehydrogenase and relatively hyperactive C lyase without impairment of cortisol secretion. This pattern resembles exaggerated adrenarche, and we postulate that these 9 patients have hyperplasia of the zona reticularis. Neither basal levels of plasma androgens (free testosterone and DHEA sulfate) nor menstrual history predicted which patients would have abnormal ACTH responses. Although 5 of 11 (45%) patients with acne alone had abnormal responses to ACTH, 10 of 14 patients with acne and hirsutism (71%) had abnormal

  9. Expression of the IGF and the aromatase/estrogen receptor systems in human adrenal tissues from early infancy to late puberty: implications for the development of adrenarche.

    Belgorosky, Alicia; Baquedano, María Sonia; Guercio, Gabriela; Rivarola, Marco A


    Adrenarche is a process of postnatal sexual maturation occurring in higher primates, in which there is an increase in the secretion of adrenal androgens. It is the consequence of a process of postnatal organogenesis characterized by the development of a new zone in the adrenal cortex, the zona reticularis (ZR). The mechanism of this phenomenon remains poorly understood, suggesting that it might be a multifactorial event. A relationship between circulating IGF-I, insulin sensitivity, and adrenal androgens has been postulated. Boys and girls have different patterns of changes in insulin sensitivity at puberty, perhaps secondary to differences in the estrogen milieu. Estrogen effects may also play a role in premature adrenarche. Peripheral or local IGF-1 actions could regulate adrenal progenitor cell proliferation and migration. Since adrenal progenitor cells as well as IGF-I and the IGF-R1 are located in the outer zone of the adrenal cortex during childhood and adolescence, this peripheral cell layer, below the capsule, may contain undifferentiated progenitor cells. Therefore, the IGF-R1 signaling pathway might positively modulate the proliferation and migration of adrenal progenitor cell to stimulate the development of adrenal zones, including ZR. However, no evidence of a direct action of IGF-I on ZR was found. In addition, a role for estrogens in the ontogenesis of ZR is suggested by the presence of aromatase (CYP19) in the subcapsular zona glomerulosa and in the adrenal medulla. Estrogens produced locally could act on ZR by interacting with estrogen receptor beta (ERbeta), but not alpha, and membrane estrogen receptor GPR-30. An estradiol-induced increase in DHEA/cortisol ratio was indeed seen in cultures of adrenocortical cells from post-adrenarche adrenals. In summary, several lines of evidence point to the action of multiple factors, such as local adrenal maturational changes and peripheral metabolic signals, on postnatal human adrenal gland ZR formation.

  10. [Mutation screening in Angiotensin II receptors, AGTR1 and AGTR2, and evaluation of AGTR1 polymorphisms C573T and A1166C in patients with premature adrenarche].

    Moura, Mônica S F; de Melo, Mônica B; Longui, Carlos Alberto; Rocha, Mylene N; Monte, Osmar


    Precocious pubarche is the appearance of pubic hair before the age of 8 years in girls and 9 years in boys. The most frequent etiology is idiopathic precocious adrenarche, suggested, after long-term follow-up, to be associated with metabolic syndrome. One of the factors involved in the genesis of precocious adrenarche is Angiotensin II (Ang II), which promotes cell proliferation and steroidogenesis through type 1 (AT1) and type 2 (AT2) receptors. In order to study Ang II receptors mutations, 50 children with idiopathic precocious adrenarche were evaluated and compared to a control group of normal individuals. Mutations were not detected in the AGTR1 and AGTR2 genes; however, two polymorphisms were identified in the AGTR1 gene: the C573T (exon 5) and the A1166C (3' untranslated region). The polymorphic allele T573 was found in 35% of the patients and 38% of controls. The polymorphic allele C1166 was present in 24% of the patients and 26% of controls. There was no statistical difference between groups. There was also no correlation between the polymorphisms and clinical and laboratory findings, as well as their family history of metabolic syndrome.

  11. Circulating TNF-alpha and IL-6 concentrations and TNF-alpha -308 G>A polymorphism in children with premature adrenarche

    Pauliina eUtriainen


    Full Text Available Premature adrenarche (PA, the early rise in adrenal androgen production leading to prepubertal signs of androgen action, has been connected with adverse metabolic features. The metabolic syndrome is characterized by low grade inflammation which in turn is associated with increases in circulating proinflammatory cytokines, like tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6. We tested the hypothesis that serum concentrations of TNF-α and IL-6 are increased in PA by studing 73 children with PA and 98 age- and gender-matched controls. Serum TNF-α and IL-6 concentrations were measured using a multiplex bead array. The subjects were genotyped for the TNF-α gene -308 G>A polymorphism (known to affect TNF-α gene transcription, and genotype-phenotype associations were studied. The mean serum TNF-α concentration was higher in the PA than control children (20.4 vs. 18.4 pg/ml, P=0.048, whereas there was no significant difference in the mean serum IL-6 concentrations between the study groups. The difference in TNF-α was not explained by excess body weight in the PA subjects as the difference remained significant after BMI-adjustment (P=0.038. In the PA group, TNF-α concentration was not associated with metabolic-endocrine features, but high IL-6 was associated with lower birth weight. There was no difference in the genotype distribution of the TNF-α gene -308 G>A polymorphism between the PA and control groups. In conclusion, PA was associated with increased serum TNF-α concentrations which, unexpectedly, were not connected with BMI or insulin resistance. The TNF-α gene -308 G>A polymorphism does not seem to be associated with the development of PA.

  12. Associations between dehydroepiandrosterone (DHEA) levels, pituitary volume, and social anxiety in children.

    Murray, Cynthia R; Simmons, Julian G; Allen, Nicholas B; Byrne, Michelle L; Mundy, Lisa K; Seal, Marc L; Patton, George C; Olsson, Craig A; Whittle, Sarah


    Early timing of adrenarche, associated with relatively high levels of dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) in children, has been linked with mental health problems, particularly anxiety. However, little is known about possible neurobiological mechanisms underlying this association. The pituitary gland is a key component of the hypothalamic-pituitary-adrenal (HPA) axis, the activation of which triggers the onset of adrenarche. The purpose of this study was to examine the extent to which pituitary gland volume mediated the relationship between levels of DHEA/DHEA-S relative to age (i.e., adrenarcheal timing) and symptoms of anxiety in 95 children (50 female, M age 9.50 years, SD 0.34 years). Relatively high DHEA and DHEA-S (DHEA/S) levels were found to be associated with larger pituitary gland volumes. There was no significant direct effect of relative DHEA/S levels on overall symptoms of anxiety. However, results supported an indirect link between relatively high DHEA/S levels and symptoms of social anxiety, mediated by pituitary gland volume. No sex differences were observed for any relationship. Our findings suggest that neurobiological mechanisms may be partly responsible for the link between relatively early adrenarche and anxiety symptoms in children. One possible mechanism for this finding is that an enlarged pituitary gland in children experiencing relatively advanced adrenarche might be associated with hyper-activity/reactivity of the HPA axis. Further research is needed to understand the role of stress in the link between adrenarcheal timing and HPA-axis function, especially in relation to the development of anxiety symptoms in children and adolescents. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Hyperandrogenism during puberty in the development of polycystic ovary syndrome.

    Nader, Shahla


    The hormonal events of puberty, from adrenarche to menarche and beyond, include the secretion of androgens as well as estrogen and P. This normal pubertal process is briefly reviewed and a physiologic role for pubertal androgens proposed. It is further suggested that the hyperandrogenic state we call polycystic ovary syndrome is a maladaptation of the advantageous role of normal pubertal androgens.

  14. Longitudinal changes in serum concentrations of adrenal androgen metabolites and their ratios by LC-MS/MS in healthy boys and girls

    Mouritsen, Annette; Søeborg, Tue; Hagen, Casper P;


    Adrenarche is characterized by steadily rising levels of adrenal androgen metabolites from 4–6 years of age. We recently described marked gender-specific differences in circulating ratios between selected adrenal androgen metabolites in a cross-sectional study. This may suggest gender differences...

  15. Endocrine evaluation of reproductive function in girls during infancy, childhood and adolescence

    Juul, Anders; Hagen, Casper P; Aksglaede, Lise


    a spectrum of disorders such as premature thelarche, premature adrenarche, central and peripheral precocious puberty, adolescent polycystic ovarian syndrome, functional ovarian hyperandrogenism, late-onset congenital adrenal hyperplasia, primary and secondary amenorrhea, and premature ovarian insufficiency....... Diagnosis of these reproductive disorders includes biochemical as well as clinical evaluation. The biochemical evaluation of reproductive function includes measurement of basal reproductive hormone levels and dynamic pituitary or adrenal hormone testing. Correct interpretation of such test results requires...

  16. Noonan syndrome: the hypothalamo-adrenal and hypothalamo-gonadal axes.

    Kelnar, Christopher J H


    The hypothalamo-pituitary-adrenal axis has not been studied systematically in Noonan syndrome (NS), despite potential concerns about other aspects of hypothalamo-pituitary function. While adrenarche may be delayed in children with constitutional growth of puberty and in isolated GH deficiency, this does not generally seem to be the case in hypergonadotrophic hypogonadism due to Turner syndrome (TS) and this is (anecdotally) the usual hormonal profile in NS children and adults. Precocious or 'exaggerated' adrenarche can be associated with intrauterine growth retardation and is a forerunner of syndrome X. Although NS neonates often have 'normal' birth weights, in some it can be artificially inflated by subcutaneous edema (as in TS, where intrauterine growth retardation is characteristic). Overall, however, a controlling role for adrenarche (whether precocious or delayed) in gonadarche in NS seems unlikely. Neither normally descended testes nor normal (even if delayed) pubertal development implies normal fertility in NS men. Interactions between fetal, neonatal, childhood and pubertal testis development and gonadal axis maturation are complex. There is probably a spectrum of abnormalities in NS, but most commonly primary gonadal failure and hypergonadotrophic hypogonadism - characteristic NS molecular genetic abnormalities - may be important for normal germ cell proliferation, development and migration. The identification of different gene defects facilitates understanding of NS phenotypic diversity and provides opportunities for prospective studies on gonadal and adrenal axes in better defined populations less subject to ascertainment bias. At a clinical level, more longitudinal data are still needed with regard to the natural history of pubertal timing, its tempo of progression and the pattern of pubertal growth.

  17. Public health implications of altered puberty timing

    Golub, Mari S; Collman, Gwen W; Foster, Paul M D


    sexual debut, potential sexual abuse, and psychosocial difficulties. Altered puberty timing is also of concern for the development of reproductive tract cancers later in life. For example, an early age of menarche is a risk factor for breast cancer. A low age at male puberty is associated...... with an increased risk for testicular cancer according to several, but not all, epidemiologic studies. Girls and, possibly, boys who exhibit premature adrenarche are at a higher risk for developing features of metabolic syndrome, including obesity, type 2 diabetes, and cardiovascular disease later in adulthood...

  18. Ovarian cysts, vaginal bleeding and hypothyroidism in a 4-year-old female with Down Syndrome: A case of Van Wyk-Grumbach Syndrome

    Suniah S. Ayub


    Full Text Available Van Wyk-Grumbach Syndrome (VWGS is a constellation of symptoms including precocious puberty without adrenarche, delayed bone age, ovarian cysts, and hypothyroidism. We report here a four-year-old Down Syndrome patient who presented for evaluation of abdominal distension, vaginal bleeding, and bilateral ovarian cysts. Her work-up and management demonstrates the importance of screening for hypothyroidism in Down Syndrome, as well as considering the diagnosis of VWGS when evaluating a patient with precocious puberty and an apparent intra-abdominal surgical process. Given the presence of ovarian masses, a surgical emergency such as ovarian torsion or rupture must be ruled out. Even when the diagnosis of VWGS is confirmed, practitioners must be vigilant to consider surgical intervention in the presence of uncontrolled vaginal bleeding, hemodynamic instability, or failure of regression of ovarian cysts with exogenous thyroid hormone replacement.

  19. Hypomelanosis of Ito associated with precocious puberty.

    Rutland, Beth M; Edgar, Mark A; Horenstein, Marcelo G


    Hypomelanosis of Ito has been associated with precocious puberty in two cases. This study reports a third case involving a female with hypomelanosis of Ito including severe mental retardation and seizure disorder with autonomic symptoms (gastroesophageal reflux and asthma). At age 5 she developed vaginal discharge, thelarche, and adrenarche. Soon after, she died of pneumonia stemming from her neurologic deficits. A postmortem examination revealed normal gonads and endocrine organs. The breasts and vulva were prematurely developed. Central nervous system findings included megalencephaly, neuronal eosinophilic inclusions, leptomeningeal neuroglial heterotopias, and cortical dysplasia. Both previously reported cases of hypomelanosis of Ito associated with precocious puberty had abnormal gonads and responded to cyproterone acetate therapy, indicating a peripheral mechanism of precocious puberty (gonadotrophin-independent). The current case, which was autopsied, lacks significant gonadal pathology, and has extensive neurologic involvement that suggests that a central mechanism of precocious puberty (gonadotrophin-dependent) can also be associated with hypomelanosis of Ito.

  20. Steroid assays in paediatric endocrinology.

    Honour, John W


    Most steroid disorders of the adrenal cortex come to clinical attention in childhood and in order to investigate these problems, there are many challenges to the laboratory which need to be appreciated to a certain extent by clinicians. The analysis of sex steroids in biological fluids from neonates, over adrenarche and puberty present challenges of specificities and concentrations often in small sample sizes. Different reference ranges are also needed for interpretations. For around 40 years, quantitative assays for the steroids and their regulatory peptide hormones have been possible using immunoassay techniques. Problems are recognised and this review aims to summarise the benefits and failings of immunoassays and introduce where tandem mass spectrometry is anticipated to meet the clinical needs for steroid analysis in paediatric endocrine investigations. It is important to keep a dialogue between clinicians and the laboratory, especially when any laboratory result does not make sense in the clinical investigation.

  1. [Acne vulgaris. The role of hormones].

    Zouboulis, C C


    Peripherally active androgens control cellular functions by binding to androgen receptors. Follicular keratinocytes and sebocytes are target cells for androgens, which, directly or indirectly, stimulate keratinocyte proliferation and the volume of sebaceous glands as well as the sebum secretion rate. Acne often begins with the adrenarche, namely with the up- regulation of adrenal synthesis of dehydroepiandrosterone sulfate, a hormone that is upstream to testosterone. The majority of acne patients exhibit normal levels of circulating androgens, while sebaceous glands from acne regions exhibit a stronger sensitivity to androgens than the sebaceous glands from other parts of the body. Hormone-like active lipids, hormones in diet and neuropeptides may also play a role in the development of acne lesions. The target of antiandrogen treatment of the skin is mainly the sebaceous gland and the primary effect is sebostasis.

  2. Pubertal outcome in a female with virilizing adrenocortical carcinoma

    Breidbart, Emily; Cameo, Tamara; Garvin, James H.; Hibshoosh, Hanina


    Adrenocortical tumors are neoplasms that rarely occur in pediatric patients. Adrenocortical carcinoma (ACC) is even more uncommon, and is an aggressive malignancy with 5-year survival of 55% in a registry series. There is a lack of information on long-term endocrine outcome in survivors. We describe a 10-year follow-up in a patient who presented at 3 years 5 months with a 1-year history of axillary odor and 6 months’ history of pubic hair development with an increased clitoral size. Androgen levels were increased and a pelvic sonogram revealed a suprarenal mass of the left kidney. The tumor was successfully removed. At 6 years 11 months, androgen levels increased again. Workup for tumor recurrence was negative and the findings likely represented early adrenarche. The patient had menarche at an appropriate time and attained a height appropriate for her family. PMID:26812773

  3. Adolescent HIV/AIDS: Issues and challenges

    Naswa Smriti


    Full Text Available Adolescence (10- 19 years is a phase of physical growth and development accompanied by sexual maturation, often leading to intimate relationships. Adolescent HIV/AIDS is a separate epidemic and needs to be handled and managed separately from adult HIV. The adolescents can be subdivided into student, slum and street youth; street adolescents being most vulnerable to HIV/AIDS. Among various risk factors and situations for adolescents contracting HIV virus are adolescent sex workers, child trafficking, child labor, migrant population, childhood sexual abuse, coercive sex with an older person and biologic (immature reproductive tract as well as psychological vulnerability. The most common mode of transmission is heterosexual, yet increasing number of perinatally infected children are entering adolescence. This is due to "bimodal progression" (rapid and slow progressors among the vertically infected children. Clinically, the HIV infected adolescents present as physically stunted individuals, with delayed puberty and adrenarche. Mental illness and substance abuse are important co-morbidities. The disclosure and declaration of HIV status to self and family is challenging and guilt in sexually infected adolescents and tendency to blame parents if vertically affected need special consideration and proper counseling. Serodiscordance of the twins and difference in disease progression of seroconcordant twins are added causes of emotional trauma. Treatment related issues revolve around the when and what of initiation of ART; the choice of antiretrovirals and their dosages; issues related to long term ADRs; sense of disinhibition following ART commencement; adherence and resistance.

  4. Hormones and Human and Nonhuman Primate Growth.

    Bernstein, Robin Miriam


    The aim of this paper was to review information pertaining to the hormonal regulation of nonhuman primate growth, with specific focus on the growth hormone (GH)-insulin-like growth factor (IGF) axis and adrenal androgens. Hormones of the GH-IGF axis are consistently associated with measures of growth - linear, weight, or both - during the growth period; in adulthood, concentrations of IGF-I, IGF-binding protein-3, and GH-binding protein are not associated with any measures of size. Comparing patterns of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) may be especially relevant for understanding whether the childhood stage of growth and development is unique to humans and perhaps other apes. Genetic, hormonal, and morphological data on adrenarche in other nonhuman primate species suggest that this endocrine transition is delayed in humans, chimpanzees, and possibly gorillas, while present very early in postnatal life in macaques. This suggests that although perhaps permitted by an extension of the pre-adolescent growth period, childhood builds upon existing developmental substrates rather than having been inserted de novo into an ancestral growth trajectory. Hormones can provide insight regarding the evolution of the human growth trajectory. © 2017 S. Karger AG, Basel.


    Binoy Kumar Mohanty


    Full Text Available BACKGROUND Precocious puberty is a common paediatric endocrine disorder seen in clinical practice. OBJECTIVE To study the various aetiologies and clinical presentations of patients presenting with sexual precocity to a tertiary care hospital. DESIGN Cross sectional study. MATERIAL AND METHODS We collected and analysed the clinical data including hormonal status of 24 consecutive patients who presented to our department from January 2014 to December 2015 for evaluation of sexual precocity. RESULTS Most of the patients presenting to us had evidence of precocious puberty (n=16, followed by premature adrenarche (n=5 and premature thelarche (n=3 respectively. The females outnumbered males in our study (68.75% of total cases. Females presenting with central precocious puberty had no appreciable cause (idiopathic in majority (85.72% of cases. While, males presenting with central precocious puberty had an organic cause (60% in majority of cases. CONCLUSIONS Precocious puberty is more common among females as compared to males. Organic lesion must be ruled out in all patients presenting with central precocious puberty especially in males.

  6. Residual manifestations of hypercortisolemia following surgical treatment in a patient with Cushing syndrome.

    Bartz, Sara K; Karaviti, Lefkothea P; Brandt, Mary L; Lopez, Monica E; Masand, Prakash; Devaraj, Sridevi; Hicks, John; Anderson, Lauren; Lodish, Maya; Keil, Meg; Stratakis, Constantine A


    Cushing Syndrome is difficult to diagnose, and the comorbidities and persistent late effects of hypercortisolemia after treatment of the primary disease are challenging for the patient and the endocrinologist. To report the case of a girl with obesity and hypertension, ultimately diagnosed with Cushing syndrome due to primary pigmented nodular adrenocortical disease. In this case, the complications of hypercortisolism persisted short term despite surgical intervention. A 4 year old morbidly obese African-American girl with developmental delay presented with hypertensive emergency in the ER and 18-month history of progressive weight gain. Her previous history included premature adrenarche, hypertension, seizures and a random high cortisol with suppressed ACTH. She was subsequently stabilized, and a diagnostic work-up persistently demonstrated elevated cortisol and suppressed ACTH. An abdominal MRI showed bilateral adrenal multinodular disease, consistent with multinodular hyperplasia of the adrenal glands. Based on these findings the patient underwent a bilateral adrenalectomy, which confirmed primary pigmented nodular adrenocortical disease. The patient had a complicated, protracted post-operative course requiring adjustment of therapy for persistent hypertension. Two months after surgery, she was readmitted to the Emergency Department with hyperpyrexia and hypertension and succumbed to the complications of sepsis. This case highlights the significant diagnostic and therapeutic challenges in treating children with Cushing syndrome. Resolution of the source of hypercortisolemia does not imply regression of hypertension or recovery of the immune system. Although the child underwent bilateral adrenalectomy, persistent consequences of prolonged severe hypercortisolism contributed to her death two months later.

  7. Marked elevation of adrenal steroids, especially androgens, in saliva of prepubertal autistic children.

    Majewska, Maria Dorota; Hill, Martin; Urbanowicz, Ewa; Rok-Bujko, Paulina; Bieńkowski, Przemysław; Namysłowska, Irena; Mierzejewski, Paweł


    Autism is diagnosed on the basis of behavioral manifestations, but its biomarkers are not well defined. A strong gender bias typifying autism (it is 4-5 times more prevalent in males) suggests involvement of steroid hormones in autism pathobiology. In order to evaluate the potential roles of such hormones in autism, we compared the salivary levels of 22 steroids in prepubertal autistic male and female children from two age groups (3-4 and 7-9 years old) with those in healthy controls. The steroids were analyzed using gas chromatography-mass spectrometry and radioimmunoassay. Statistical analysis (ANOVA) revealed that autistic children had significantly higher salivary concentrations of many steroid hormones (both C21 and C19) than control children. These anomalies were more prominent in older autistic children and in boys. The levels of androgens (androstenediol, dehydroepiandrosterone, androsterone and their polar conjugates) were especially increased, indicative of precocious adrenarche and predictive of early puberty. The concentrations of the steroid precursor, pregnenolone, and of several pregnanolones were also higher in autistic than in healthy children, but cortisol levels were not different. Some steroids, whose levels are raised in autism (allopregnanolone, androsterone, pregnenolone, dehydroepiandrosterone and their sulfate conjugates) are neuroactive and modulate GABA, glutamate, and opioid neurotransmission, affecting brain development and functioning. These steroids may contribute to autism pathobiology and symptoms such as elevated anxiety, sleep disturbances, sensory deficits, and stereotypies among others. We suggest that salivary levels of selected steroids may serve as biomarkers of autism pathology useful for monitoring the progress of therapy.

  8. Impact of Early Postnatal Androgen Exposure on Voice Development

    Grisa, Leila; Leonel, Maria L.; Gonçalves, Maria I. R.; Pletsch, Francisco; Sade, Elis R.; Custódio, Gislaine; Zagonel, Ivete P. S.; Longui, Carlos A.; Figueiredo, Bonald C.


    Background The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. Methods The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Results Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Conclusions Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors. PMID:23284635

  9. Natural history of chronic hepatitis B virus infection from infancy to adult life - the mechanism of inflammation triggering and long-term impacts.

    Wu, Jia-Feng; Chang, Mei-Hwei


    Chronic hepatitis B virus (HBV) infection in endemic areas usually starts since infancy and early childhood and persists lifelong. The clinical course varies among different chronic infected subjects. Majority of chronic HBV infected children present with immune-tolerant status initially, experience the immune clearance phase with various degree of liver injury during or beyond puberty, and then enter the inactive phase after hepatitis B e antigen (HBeAg) seroconversion. Part of them may have HBV DNA titers elevation with hepatitis flare after HBeAg seroconversion, the so call HBeAg-negative hepatitis flare. Liver cirrhosis, and even hepatocellular carcinoma may develop afterward.The complex course of chronic HBV infection is associated with the age/route of viral acquisition, host factors such as immune and endocrine factors, viral factors, and host-viral interactions. The adrenarche and puberty onset modulate the start of immune clearance and the severity of liver inflammation in chronic HBV infected children. The genotype and phenotype of human cytokines, innate immunity, and human leukocyte antigens are also associated with the onset of immune clearance of HBV and severity of inflammation. Immune escape HBV mutant strains, emerged during the immune clearance phase under host immune surveillance, may cause different impacts on viral biosynthesis, host immune responses, and clinical course.Early events in childhood during chronic HBV infection may serve as important predictors for the later outcome in adulthood. Understanding the mechanisms triggering liver inflammation and their long-term impacts may enhance the development of better and earlier therapeutic strategies for patients with chronic HBV infection.

  10. Etiology of precocious puberty, 10 years study in Endocrine Reserch Centre (Firouzgar, Tehran

    Fatemeh Safari


    Full Text Available Background: Precocious puberty, as early physical development and low final height might lead to psychosocial problems.Objective: To evaluate etiology and clinical feature of precocious puberty in a cohort of Iranian children.Materials and Methods: In this case-series study, 44 girls and 8 boys with precocious puberty referred to Endocrine Reserch Centre (Firouzgar, Institute of Endocrinology and Metabolism (Hemmat Campus, were examined in a 10 years period of time. Results: Mean age of girls and boys was 7.43±1.4 years and 5.8±2.1 years respectively. Most of the patients fell within the age category of 7-7.9 years old (40.9% for girls and 50% for boys. Patients, concerning etiology of precocious puberty were classified in three categories: 42.6% of patients had central precocious puberty (CPP, including idiopathic CPP (87.5% and neurogenic CPP (12.5%. 23.3% of patients had peripheral precocious puberty (PPP, including congenital adrenal hyperplasia (CAH (42.8%, ovarian cysts (28.4%, McCune-Albright syndrome (14.2% and adrenal carcinoma (14.2%. 34.1% of girls and 25% of boys had normal variant puberty including premature thelarche (57%, premature adrenarche (38% as well as premature menarche (4.7%l. Conclusion: The most common etiology of precocious puberty in girls was idiopathic central precocious puberty and premature thelarche, while in boys they were neurogenic central precocious puberty and CAH. Therefore precocious puberty in girls is usually benign. In boys, CNS anomalies should first be considered in the differential diagnosis of CPP. Therefore brain Magnetic Resonance Imaging (MRI is mandatory in all cases.

  11. Impact of early postnatal androgen exposure on voice development.

    Leila Grisa

    Full Text Available BACKGROUND: The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT in childhood. METHODS: The long-term effects of androgen exposure on the fundamental vocal frequency (F0, vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years and 10 adolescent (13.6 to 17.8 years female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. RESULTS: Of the 19 subjects, 17 (89% had been diagnosed with ACT before 4 years of age, 1 (5% at 8.16 years, and 1 (5% at 10.75 years. Androgen exposure (2 to 30 months was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19 of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. CONCLUSIONS: Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors.

  12. Studies to confirm the source of 11 beta-hydroxyandrostenedione.

    Holownia, P; Owen, E J; Conway, G S; Round, J; Honour, J W


    In a longitudinal study of 82 children we found a gradual rise in median plasma concentrations of 11 beta-hydroxyandrostenedione (11 beta-OH-A4) from 2.5 to 6.4 nmol/l during childhood which was similar in both sexes. This could reflect changes in adrenal function during the adrenarche and sexual maturation. Plasma concentrations of 11 beta-OH-A4 in adults follow the patterns of cortisol secretion. In patients with diseases of the adrenal cortex, the plasma concentrations of 11 beta-OH-A4 were consistent with the pathology of each condition. In women with polycystic ovaries (PCO) undergoing gonadotrophic stimulation for in vitro fertilization and embryo transfer, 11 beta-OH-A4 (median = 3.8 nmol/l), testosterone and androstenedione, were raised when compared to women with normal ovaries (11 beta-OH-A4 median = 2.6 nmol/l). Follicular fluid has concentrations of 11 beta-OH-A4 six to twelve times greater than plasma levels and in women with PCO, 11 beta-OH-A4 concentrations were lower than in women with normal ovaries, which is consistent with an inhibition of ovarian 11 beta-hydroxylase. Granulosa cells in vitro demonstrated the production of 11 beta-OH-A4 by side chain cleavage of cortisol. These data support an adrenal source for 11 beta-OH-A4 but the raised plasma concentrations in women with polycystic ovary syndrome (PCOS) may reflect the excess androgen output from the ovary. 11 beta-OH-A4 may therefore be an additional marker for ovarian dysfunction.

  13. Recommendations for treatment of nonclassic congenital adrenal hyperplasia (NCCAH): an update.

    Trapp, Christine M; Oberfield, Sharon E


    Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders. 21-Hydroxylase deficiency, in which there are mutations in CYP21A2 (the gene encoding the adrenal 21-hydroxylase enzyme), is the most common form (90%) of CAH. In classic CAH there is impaired cortisol production with diagnostic increased levels of 17-OH progesterone. Excess androgen production results in virilization and in the newborn female may cause development of ambiguous external genitalia. Three-fourths of patients with classic CAH also have aldosterone insufficiency, which can result in salt-wasting; in infancy this manifests as shock, hyponatremia and hyperkalemia. CAH has a reported incidence of 1:10,000-1:20,000 births although there is an increased prevalence in certain ethnic groups. Nonclassic CAH (NCCAH) is a less severe form of the disorder, in which there is 20-50% of 21-hydroxylase enzyme activity (vs. 0-5% in classic CAH) and no salt wasting. The degree of symptoms related to androgen excess is variable and may be progressive with age, although some individuals are asymptomatic. NCCAH has an incidence of 1:1000-1:2000 births (0.1-0.2% prevalence) in the White population; an even higher prevalence is noted in certain ethnic groups such as Ashkenazi Jews (1-2%). As many as two-thirds of persons with NCCAH are compound heterozygotes and carry a severe and mild mutation on different alleles. This paper discusses the genetics of NCCAH, along with its variable phenotypic expression, and reviews the clinical course in untreated patients, which includes rapid early childhood growth, advanced skeletal age, premature adrenarche, acne, impaired reproductive function in both sexes and hirsutism as well as menstrual disorders in females. Finally, it addresses treatment with glucocorticoids vs. non treatment and other therapies, particularly with respect to long term issues such as adult metabolic disease including insulin resistance, cardiovascular disease, metabolic syndrome

  14. 青春期前痤疮的研究进展%Prepubertal acne

    王琪; 张国毅; 尹跃平


    青春期前痤疮是儿童期痤疮的一种,多发生于7岁以后青春期体征出现以前,表现为以粉刺样损害为主的皮损.其发病主要与青春期发育初期肾上腺功能初现引起的雄激素分泌增高有关,痤疮丙酸杆菌感染及高雄激素血症在痤疮发病中也有重要作用.青春期前痤疮的严重程度影响青春期痤疮的发展,在诊疗时需仔细询问病史及家族史.并做相应的实验室检查以排除其他疾病影响引起高雄激素血症性痤疮.在治疗时根据患儿年龄、皮损数量选择合适的治疗方法,治疗方案尽量简单.%Prepubertal acne,a kind of childhood acne,usually occurs from 7 years of age to the emergence of puberty signs in children.Comedo-like lesions are the main presentation of prepubertal acne.Its pathogenesis is mainly associated with increased secretion of androgen caused by adrenarche in early puberty.Furthermore,Propionibacterium acne infection and hyperandrogenism also play important roles in the occurrence of acne.The severity of prepubertal acne can affect the development of acne,thus careful inquiry of medical history and family history is suggested for the diagnosis and treatment of acne.Also,relevant laboratory examinations are needed to exclude hyperandrogenism-associated acne caused by other diseases.Therapeutic strategies should be selected according to patients' age and the number of skin lesions,and be as simple as possible.

  15. Reduced quality and accelerated follicle loss with female reproductive aging - does decline in theca dehydroepiandrosterone (DHEA) underlie the problem?

    Ford, Judith H


    suggested by successful interventions to date. In humans and primates that undergo adrenarche, the adrenal zona reticularis (ZR) is the major site of DHEA production, however this is also reduced with age. Concomitant loss in function of the ZR might account for the acceleration in the rate of aging seen in humans in the late thirties' age group.

  16. Precocious puberty: clinical and endocrine profile and factors indicating neurogenic precocity in Indian children.

    Bajpai, Anurag; Sharma, Jyoti; Kabra, Madhulika; Kumar Gupta, Arun; Menon, P S N


    The objective of this study was to evaluate the clinical and endocrine profile of patients with precocious puberty followed up in a tertiary care hospital. Records of 140 patients (114 girls, 26 boys) with precocious puberty were reviewed. Clinical features including age of onset, stage of pubertal development, presenting symptoms, features suggestive of CNS involvement and family history were analyzed. Endocrine investigations included basal and GnRH-stimulated levels of LH and FSH as well as 17OHP, DHEA, hCG and thyroid profile. Abdominal and pelvic ultrasonography and CNS imaging were correlated with clinical features. Girls outnumbered boys in this series (4.4:1). Neurogenic central isosexual precocious puberty (CIPP) was more common in boys (10 out of 18, 55.6%) than girls (16 out of 77, 20.8%). The most common cause of neurogenic CIPP was hypothalamic hamartoma present in five girls and four boys. Other causes of neurogenic CIPP included neurotuberculosis, pituitary adenoma, hydrocephalus, post radiotherapy, CNS tumors and malformations. Peripheral precocious puberty (PPP) was secondary to adrenal causes in boys and ovarian cysts in girls. Benign variants of precocious puberty, such as premature thelarche and premature adrenarche, were present in 23 and six girls, respectively. Hypothyroidism was present in four girls and McCune-Albright syndrome in one girl. Girls with neurogenic CIPP had a lower age of onset as compared to idiopathic CIPP (3.6 +/- 2.7 years vs 5.4 +/- 2.5 years, p = 0.014). The lowest age of onset was seen in girls with hypothalamic hamartoma (1.6 +/- 0.9 years). Forty-seven girls with CIPP (seven neurogenic and 40 idiopathic) presented after the age of 6 years. Features of CNS involvement, in the form of seizures, mental retardation, raised intracranial tension or focal neurological deficits, were present in seven girls (43.8%) and four boys (40%), and gelastic seizures were present in three children. Girls with CIPP had greater bone age

  17. 青春期前不同时长脱氢表雄酮暴露对成年雌鼠生殖力的影响%Prepubal hyperandrogen exposure induces reproductive changes in adult female rats

    陈婕; 谈勇


    Objective Androgen is an important precursor for the synthesis of estrogen in vivo and is involved in the regulation of female reproductive function.In this study, we explored the influence of different lengths of prepubertal exposure to hyperandrogen on the reproductive function of adult female rats. Methods Twenty-five 23-day-old female rats were equally randomized into five groups:oil control, 2-wk dehydroepiandrosterone (DHEA), 4-wk DHEA, 6-wk DHEA, and 8-wk DHEA, injected with oil or DHEA daily for 2, 4, 6, and 8 weeks respectively, and mated at 80 days old.We detected serum concentrations of total testosterone (tT), estradiol (E2), follicle-stimulating hormone ( FSH) and luteinizing hormone ( LH) by ELISA, observed the time of vaginal opening and changes of the estrous cycle, and recorded the rates of mating and pregnancy, the number of the offspring and their survival rate. Results The tT lev-el was elevated after 2 weeks of DHEA injection, fell to normal after drug withdrawal in the 2-wk and 4-wk DHEA groups, and remained at a high level in the 6-wk group.The E2 level was markedly increased in at 2 and 4 weeks but showed a falling trend at 6 and 8 weeks. DHEA injection did not change the level of FSH significantly but re-markably lifted that of LH with the increased concentration of tT.The vaginal opening time was significantly advanced in the 2-wk DHEA group as compared with the controls ([26.60 ±0.89] d vs [35.20 ± 2.49] d, P0.05). Conclusion Prepubertal expo-sure to hyperandrogen may advance adrenarche and gonadarche and affect the initiation of the sexual gland function in female rats.Impro-ving the hyperandrogen status in the early pubertal stage can reverse the disorder of the estrous cycle, while long-term exposure to DHEA may significantly reduce the fecundity at the childbearing age.%目的:雄激素是体内合成雌激素的重要前体,参与女性生殖功能的调控。文中探讨了青春期前接受不同时长的高雄激素刺激