scholarly journals TRANSITION IN ENDOCRINOLOGY: Induction of puberty

2014 ◽  
Vol 170 (6) ◽  
pp. R229-R239 ◽  
Author(s):  
Leo Dunkel ◽  
Richard Quinton
Keyword(s):  
Pubertal Timing ◽  
Hormone Replacement ◽  
Adult Life ◽  
Charge Syndrome ◽  
Delayed Puberty ◽  
Congenital Defects ◽  
Hypogonadotrophic Hypogonadism ◽  
Future Fertility ◽  
Pubertal Delay ◽  
Sexual Characteristics

Puberty is the period during which we attain adult secondary sexual characteristics and reproductive capability. Its onset depends upon reactivation of pulsative GNRH, secretion from its relative quiescence during childhood, on the background of intact potential for pituitary–gonadal function. This review is intended: to highlight those current practices in diagnosis and management that are evidence based and those that are not; to help clinicians deal with areas of uncertainty with reference to physiologic first principles; by sign-posting relevant data arising from other patient groups with shared issues; to illustrate how recent scientific advances are (or should be) altering clinician perceptions of pubertal delay; and finally, to emphasise that the management of men and women presenting in advanced adult life with absent puberty cannot simply be extrapolated from paediatric practice. There is a broad spectrum of pubertal timing that varies among different populations, separated in time and space. Delayed puberty usually represents an extreme of the normal, a developmental pattern referred to as constitutional delay of growth and puberty (CDGP), but organic defects of the hypothalamo–pituitary–gonadal axis predisposing to hypogonadism may not always be initially distinguishable from it. CDGP and organic, or congenital hypogonadotrophic hypogonadism are both significantly more common in boys than girls. Moreover, around 1/3 of adults with organic hypogonadotrophic hypogonadism had evidence of partial puberty at presentation and, confusingly, some 5–10% of these subsequently may exhibit recovery of endogenous gonadotrophin secretion, including men with Kallmann syndrome. However, the distinction is crucial as expectative (‘watch-and-wait’) management is inappropriate in the context of hypogonadism. The probability of pubertal delay being caused by organic hypogonadism rises exponentially both with increasing age at presentation and the presence of associated ‘red flag’ clinical features. These ‘red flags’ comprise findings indicating lack of prior ‘mini-puberty’ (such as cryptorchidism or micropenis), or the presence of non-reproductive congenital defects known to be associated with specific hypogonadal syndromes, e.g. anosmia, deafness, mirror movements, renal agenesis, dental/digital anomalies, clefting or coloboma would be compatible with Kallmann (or perhaps CHARGE) syndrome. In children, interventions (whether in the form or treatment or simple reassurance) have been historically directed at maximising height potential and minimising psychosocial morbidity, though issues of future fertility and bone density potential are now increasingly ‘in the mix’. Apubertal adults almost invariably harbour organic hypogonadism, requiring sensitive acknowledgement of underlying personal issues and the timely introduction of sex hormone replacement therapy at more physiological doses.

Delayed Puberty

2020 ◽  
Author(s):  
Amanda French
Keyword(s):  
Pubertal Timing ◽  
Hormone Replacement ◽  
Hypogonadotropic Hypogonadism ◽  
Disease Process ◽  
Optimal Growth ◽  
Underlying Disease ◽  
Delayed Puberty ◽  
Hypergonadotropic Hypogonadism ◽  
Pubertal Delay ◽  
Constitutional Delay

Although common, delayed puberty can be distressing to patients and families.   Careful assessment is necessary to ensure appropriate physical and social development in patients that require intervention to reach pubertal milestones and achieve optimal growth.  Most pubertal delay is from lack of activation of the hypothalamic-pituitary-gonadal axis which then results in a functional or physiologic GnRH deficiency.  The delay may be temporary or permanent.  Constitutional delay (CDGP), also referred to as self-limited delayed puberty (DP), describes children on the extreme end of normal pubertal timing and is the most common cause of delayed puberty, representing about one third of cases.  Hypergonadotropic hypogonadism (primary hypogonadism) results from a failure of the gonad itself, and hypogonadotropic hypogonadism (secondary hypogonadism) results from a failure of the hypothalamic-pituitary axis, which is usually caused by another process, often systemic.  Diagnosis is based on history and examination.  Treatment is based on the underlying cause of pubertal delay and may include hormone replacement.  Involving a pediatric endocrinologist should be considered.  Appropriate counseling and ongoing support are important for all patients and families, regardless of underlying disease process.   This review contains 4 figures, 4 tables, and 32 references. Keywords: puberty, delayed puberty, hypogonadism, hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, menarche, thelarche, constitutional delay and growth in puberty, Turner syndrome

Delayed Puberty

2020 ◽  
Author(s):  
Amanda French
Keyword(s):  
Pubertal Timing ◽  
Hormone Replacement ◽  
Hypogonadotropic Hypogonadism ◽  
Disease Process ◽  
Optimal Growth ◽  
Underlying Disease ◽  
Delayed Puberty ◽  
Hypergonadotropic Hypogonadism ◽  
Pubertal Delay ◽  
Constitutional Delay

Although common, delayed puberty can be distressing to patients and families.   Careful assessment is necessary to ensure appropriate physical and social development in patients that require intervention to reach pubertal milestones and achieve optimal growth.  Most pubertal delay is from lack of activation of the hypothalamic-pituitary-gonadal axis which then results in a functional or physiologic GnRH deficiency.  The delay may be temporary or permanent.  Constitutional delay (CDGP), also referred to as self-limited delayed puberty (DP), describes children on the extreme end of normal pubertal timing and is the most common cause of delayed puberty, representing about one third of cases.  Hypergonadotropic hypogonadism (primary hypogonadism) results from a failure of the gonad itself, and hypogonadotropic hypogonadism (secondary hypogonadism) results from a failure of the hypothalamic-pituitary axis, which is usually caused by another process, often systemic.  Diagnosis is based on history and examination.  Treatment is based on the underlying cause of pubertal delay and may include hormone replacement.  Involving a pediatric endocrinologist should be considered.  Appropriate counseling and ongoing support are important for all patients and families, regardless of underlying disease process.   This review contains 4 figures, 4 tables, and 32 references. Keywords: puberty, delayed puberty, hypogonadism, hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, menarche, thelarche, constitutional delay and growth in puberty, Turner syndrome

Delayed Puberty

2020 ◽  
Author(s):  
Amanda French
Keyword(s):  
Pubertal Timing ◽  
Hormone Replacement ◽  
Hypogonadotropic Hypogonadism ◽  
Disease Process ◽  
Optimal Growth ◽  
Underlying Disease ◽  
Delayed Puberty ◽  
Hypergonadotropic Hypogonadism ◽  
Pubertal Delay ◽  
Constitutional Delay

Although common, delayed puberty can be distressing to patients and families.   Careful assessment is necessary to ensure appropriate physical and social development in patients that require intervention to reach pubertal milestones and achieve optimal growth.  Most pubertal delay is from lack of activation of the hypothalamic-pituitary-gonadal axis which then results in a functional or physiologic GnRH deficiency.  The delay may be temporary or permanent.  Constitutional delay (CDGP), also referred to as self-limited delayed puberty (DP), describes children on the extreme end of normal pubertal timing and is the most common cause of delayed puberty, representing about one third of cases.  Hypergonadotropic hypogonadism (primary hypogonadism) results from a failure of the gonad itself, and hypogonadotropic hypogonadism (secondary hypogonadism) results from a failure of the hypothalamic-pituitary axis, which is usually caused by another process, often systemic.  Diagnosis is based on history and examination.  Treatment is based on the underlying cause of pubertal delay and may include hormone replacement.  Involving a pediatric endocrinologist should be considered.  Appropriate counseling and ongoing support are important for all patients and families, regardless of underlying disease process.   This review contains 4 figures, 4 tables, and 32 references. Keywords: puberty, delayed puberty, hypogonadism, hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, menarche, thelarche, constitutional delay and growth in puberty, Turner syndrome

Testosterone Therapy for Pubertal delay

1992 ◽  
Vol 13 (1) ◽  
pp. 5-39
Keyword(s):  
Anabolic Steroids ◽  
Pubic Hair ◽  
Height Velocity ◽  
Delayed Puberty ◽  
Secondary Sexual Characteristics ◽  
Self Image ◽  
Pubertal Delay ◽  
Constitutional Delay ◽  
Sexual Characteristics ◽  
Age Appropriate

Despite considerable variation in the age at which puberty normally begins, a male adolescent who has demonstrated neither testicular nor pubic hair growth by 14 years of age is considered to have delayed puberty. Although such delay may indicate hypopituitarism or isolated gonadotropin deficiency, most commonly it represents a normal variation, termed "constitutional delay in growth and maturation." Such patients eventually will enter puberty and achieve normal sexual maturation and adult height. However, during adolescence, such delays may be accompanied by impaired self-image and social isolation. Under these conditions, many pediatric endocrinologists advocate short-term use of anabolic steroids. Such therapy is aimed at accelerating height velocity during the ensuing year, accompanied by the development of age-appropriate secondary sexual characteristics.

scholarly journals Chronic Psychosocial Stress and Experimental Pubertal Delay Affect Socioemotional Behavior and Amygdala Functional Connectivity in Adolescent Female Rhesus Macaques

2020 ◽  
Author(s):  
Melanie Pincus ◽  
Jodi S. Godfrey ◽  
Eric Feczko ◽  
Eric Earl ◽  
Oscar Miranda-Dominguez ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Psychosocial Stress ◽  
Pubertal Timing ◽  
High Stress ◽  
Delayed Puberty ◽  
Adolescent Female ◽  
Pubertal Delay ◽  
Chronic Psychosocial Stress ◽  
Effects Of Stress ◽  
The Impact

ABSTRACTIn females, pubertal onset appears to signal the opening of a window of increased vulnerability to the effects of stress on neurobehavioral development. What is the impact of pubertal timing on this process? We assessed the effects of pubertal timing and stress on behavior and amygdala functional connectivity (FC) in adolescent female macaques, whose social hierarchy provides an ethologically valid model of chronic psychosocial stress. Monkeys experienced puberty spontaneously (n=34) or pubertal delay via Lupron treatment from age 16-33 months (n=36). We examined the effects of stress (continuous dimension spanning dominant/low-stress to subordinate/high-stress) and experimental pubertal delay (Lupron-treated vs. Control) on socioemotional behavior and FC at 43-46 months, after all animals had begun puberty. Regardless of treatment, subordinate monkeys were more submissive and less affiliative, and exhibited weaker FC between amygdala and dorsolateral prefrontal cortex and stronger FC between amygdala and temporal pole. Regardless of social rank, Lupron-treated monkeys were also more submissive, less affiliative, and explored less in a “Human Intruder” task but were less anxious than untreated monkeys; they exhibited stronger FC between amygdala and orbitofrontal cortex. No interactions between rank and Lupron treatment were observed. These data suggest that some of the effects of chronic subordination stress and delayed puberty overlap behaviorally, such that late-onset puberty-linked exposure to female hormones mimics chronic stress. In the brain, however, delayed puberty and subordination stress had separable effects, suggesting that the overlapping socioemotional outcomes may be mediated by distinct neuroplastic mechanisms. To gain further insights, additional longitudinal studies are required.

scholarly journals Genetic regulation in pubertal delay

2019 ◽  
Vol 63 (3) ◽  
pp. R37-R49 ◽  
Author(s):  
Sasha R Howard
Keyword(s):  
Genetic Factors ◽  
Clinical Presentation ◽  
Late Onset ◽  
Pubertal Timing ◽  
Genetic Regulation ◽  
Delayed Puberty ◽  
Pubertal Delay ◽  
History Of ◽  
Timing Of Puberty ◽  
Hormone System

Delayed puberty represents the clinical presentation of a final common pathway for many different pathological mechanisms. In the majority of patients presenting with significantly delayed puberty, there is a clear family history of delayed or disturbed puberty, and pubertal timing is known to be a trait with strong heritability. Thus, genetic factors clearly play a key role in determining the timing of puberty, and mutations in certain genes are recognised as responsible for delayed or absent puberty in a minority of patients. Through the identification of causal genetic defects such as these we have been able to learn a great deal about the pathogenesis of disrupted puberty and its genetic regulation. Firstly, deficiency in key genes that govern the development of the gonadotropin-releasing hormone system during fetal development may result in a spectrum of conditions ranging from isolated delayed puberty to absent puberty with anosmia. Secondly, a balance of inhibitory and excitatory signals, acting upstream of GnRH secretion, are vital for the correct timing of puberty. These act to repress the hypothalamic–pituitary–gonadal axis during mid-childhood and allow it to reactivate at puberty, and alterations in this equilibrium can cause delayed (or precocious) puberty. Thirdly, disturbances of energy metabolism inputs to the kisspeptin–GnRH system may also lead to late onset of puberty associated with changes in body mass.

Recent advances in the understanding and management of delayed puberty

2015 ◽  
Vol 101 (5) ◽  
pp. 481-488 ◽  
Author(s):  
Christina Wei ◽  
Elizabeth Clare Crowne
Keyword(s):  
Environmental Factors ◽  
Pulse Generator ◽  
Pubertal Development ◽  
Hormone Replacement ◽  
Sex Steroid ◽  
Delayed Puberty ◽  
Physiological Basis ◽  
Releasing Hormone ◽  
Hypogonadotrophic Hypogonadism ◽  
Recent Advances

Delayed puberty, especially in boys, is a common presentation in paediatrics. Recent advances have improved our understanding of the neuroendocrine, genetic and environmental factors controlling pubertal development, and hence inform the pathophysiology of delayed puberty. The discovery of kisspeptin signalling through its receptor identified neuroendocrine mechanisms controlling the gonadotrophin-releasing hormone (GnRH) pulse generator at the onset of puberty. Genetic mechanisms from single gene mutations to single nucleotide polymorphism associated with delayed puberty are being identified. Environmental factors, including nutritional factors and endocrine disruptors, have also been implicated in changes in secular trends and abnormal timing of puberty. Despite these advances, the key clinical question is to distinguish delayed puberty associated with an underlying pathology or hypogonadism from constitutional delay in growth and puberty, which remains challenging as biochemical tests are not always discriminatory. The diagnostic accuracies of newer investigations, including 36-hour luteinising hormone releasing hormone (LHRH) tests, GnRH-agonist tests, antimullerian hormone and inhibin-B, require further evaluation. Sex hormone replacement remains the main available treatment for delayed puberty, the choice of which is largely dictated by clinical practice and availability of the various sex steroid preparations. Spontaneous reversal of hypogonadism has been reported in boys with idiopathic hypogonadotrophic hypogonadism after a period of sex steroid treatment, highlighting the importance of reassessment at the end of pubertal induction. Novel therapies with a more physiological basis such as gonadotrophins or kisspeptin-agonist are being investigated for the management of hypogonadotrophic hypogonadism. Careful clinical assessment and appreciation of the normal physiology remain the key approach to patients with delayed puberty.

scholarly journals Diagnosis of male central hypogonadism during childhood

2021 ◽  
Author(s):  
Romina P Grinspon ◽  
Sebastián Castro ◽  
Franco G Brunello ◽  
Gabriela Sansó ◽  
María Gabriela Ropelato ◽  
...  
Keyword(s):  
Psychosocial Adjustment ◽  
Bone Mineralization ◽  
Hormone Replacement ◽  
Hypogonadotropic Hypogonadism ◽  
Serum Levels ◽  
Kinase Domain ◽  
Delayed Puberty ◽  
Tyrosine Kinase Domain ◽  
Mineral Density ◽  
Sexual Characteristics

Abstract The diagnosis of male central (or hypogonadotropic) hypogonadism, typically based on low LH and testosterone levels, is challenging during childhood since both hormones are physiologically low from the 6 th month until the onset of puberty. Conversely, FSH and anti-Müllerian hormone (AMH), which show higher circulating levels during infancy and childhood, are not used as biomarkers for the condition. We report the case of a 7-year-old boy with a history of bilateral cryptorchidism, who showed repeatedly low FSH and AMH serum levels during prepuberty. Unfortunately, the diagnosis could not be ascertained until he presented with delayed puberty at the age of 14 years. A GnRH test showed impaired LH and FSH response. By then, his growth and bone mineralization were partially impaired. Gene panel sequencing identified a variant in exon 15 of FGFR1, affecting the tyrosine kinase domain of the receptor, involved in GnRH neuron migration and olfactory bulb morphogenesis. Testosterone replacement was started, which resulted in the development of secondary sexual characteristics and partial improvement of bone mineral density. This case illustrates the difficulty in making the diagnosis of central hypogonadism in boys during childhood based on classical criteria, and how serum FSH and AMH assessment may be helpful to suspect it before the age of puberty, and confirm it using next-generation sequencing. The possibility of making an early diagnosis of central hypogonadism may be useful for a timely start of hormone replacement therapy, and to avoid delays that could affect growth and bone health as well as psychosocial adjustment.

scholarly journals MON-355 Charge Syndrome: Unusual Cause of Hypogonadism Leading to Osteoporosis

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ankur Modi ◽  
Veronica Piziak
Keyword(s):  
Bone Mineralization ◽  
Mass Density ◽  
Hormone Replacement ◽  
Hypogonadotropic Hypogonadism ◽  
Charge Syndrome ◽  
Delayed Puberty ◽  
Bone Mass Density ◽  
Z Score ◽  
Total Hip

Abstract CHARGE syndrome is an unusual cause of hypogonadism; it is characterized by coloboma, heart defect, ateresia choanae, retarded growth and development, genital hypoplasia and ear anomalies. Two-thirds of affected patients have a mutation within the chromodomain helicase DNA-binding protein-7 gene, which is involved in embryonic development. The involvement of this gene in the pathogenesis of isolated idiopathic hypogonadotropic hypogonadism (HH) has been postulated. The reported incidence of this syndrome ranges from 0.1–0.2/10000 (1). A 24 year old female presented to our facility for further management of her HH and osteoporosis in the setting of her CHARGE syndrome. She was born full-term and diagnosed with this condition at the age of 6. Formal genetic testing as an adult demonstrated mutation within the CHD7 gene (chr 8:61,757,970). She had delayed puberty secondary to her hypogonadism; she was not treated with HRT as benefits were not considered significantly sufficient. She subsequently developed osteoporosis at the age of 20 which was treated at an outside facility with pamidronate IV Q4 months along with calcium and Vitamin D supplementation. Her initial Dual-energy X-ray absorptiometry (DXA) showed scoliosis in the lumbar spine [bone mass density (BMD): 0.514,osteoporosis by Z-score] with total hip showing BMD: 0.738,osteopenia by Z-score. Follow-up DXA after 3 years showed statistically significant improvement in bone mineralization of her L-spine [BMD: 0.595, +16%] and total hip [BMD: 0.777, +13.5%]. She presented to our facility in 2018 with labs showing normal calcium and 25-OH D; treatment with pamidronate was continued. She had a repeat DXA in 2019 which showed Z-scores of 0 in the left and right femoral necks. She was given the option of continued treatment for her osteoporosis versus monitoring and chose the latter with follow-up DXA. Hypogonadotropic hypogonadism is associated with delays in puberty or pubertal arrest. Luteinizing Hormone Releasing Hormone and HCG tests should be performed within the four months of life or at puberty in cases of hypogenitalism. GH deficiency should be investigated as a cause for growth retardation with GH stimulation levels. Hormone replacement is often required at puberty for females and is indicated for prevention of osteoporosis. Radiological testing with DXA scan should be included. Early proper endocrinological assessment and management is essential for adequate sexual development in these patients; this leads to improved overall quality of life along with prevention of serious morbidities, including bone demineralization (2). 1. Blake K D, Prasad C. CHARGE syndrome. Orphanet Journal of Rare Diseases 2006, 1:34. 2. Foppiani L, Maffe A. CHARGE syndrome as unusual cause of hypogonadism: endocrine and molecular evaluation. Andrologia (2010). 42: 326–330.

scholarly journals Menarche in primary ovarian insufficiency after a month of hormone replacement therapy: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Biwen Cheng
Keyword(s):  
Replacement Therapy ◽  
Hormone Replacement ◽  
Estrogen Therapy ◽  
Primary Ovarian Insufficiency ◽  
Hormonal Replacement Therapy ◽  
Delayed Puberty ◽  
Ovarian Insufficiency ◽  
Breakthrough Bleeding ◽  
Hormonal Replacement ◽  
Ovarian Dysgenesis

Abstract Background Gynecologic anomalies, including uterine agenesis and ovarian dysgenesis, are some of the several differential diagnoses in adolescent females with primary amenorrhea and delayed puberty. Primary ovarian insufficiency is reported in the clinical practice of reproductive endocrinology can be determined by conducting sex hormone tests to evaluate the hypothalamic-pituitary-ovarian axis. However, confirmation of Mullerian agenesis by image modalities can be extremely challenging. Once the diagnosis is established, breakthrough bleeding usually occurs 2 to 3 years after hormonal replacement therapy. Case presentation We report a case of a seventeen year old Taiwanese female, 46 XX karyotype, with ovarian dysgenesis and an initial tentative diagnosis of uterine agenesis who experienced a breakthrough bleeding after a month of hormonal replacement therapy. Conclusions The breakthrough bleeding after a month of estrogen therapy in primary ovarian insufficiency is uncommon, and the diagnosis of the absent uterus can have an extensive psychological impact on patients and their families.

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