Alan D Rogol

• MD/Ph.D
• Professor Emeritus at University of Virginia

Purpose of review Throughout history, competitive sport has been categorized by sex. Since the 1930s, sporting organizations have implemented various methods of confirming sex for competition in the female category. These policies primarily impact individuals with differences of sex development (DSD), whose biology falls outside the binary of male/...

From antiquity, Man has been fascinated by at least two processes of testicular function: virility and reproduction; their biological basis was uncovered beginning in the mid-19th century. We have divided the search into 3 epochs: the speculative and observational, the experimental, and the biochemical/physiological. The first begins with Susruta,...

Human growth hormone (hGH) has been in clinical use for children with GH deficiency (GHD) since the late 1950s. The original formulations were considered very safe with few adverse events reported. That changed remarkably in 1985 when the first patients with GHD, who had been treated with cadaveric hGH, were diagnosed with Creutzfeldt-Jakob disease...

Organized sports are governed by specific rules which aim to create or preserve fair play. An unfair advantage can be obtained by the use of specific substances or methods, also referred to as doping. The World Anti-Doping Agency (WADA) leads the international doping-free sport movement and annually publishes the List of Prohibited Substances and M...

The Endocrine Society formally addressed the issue of retirement for its members for the first time in a Workshop held on June 4 at ENDO 2024 in Boston, Massachusetts. Preparation for the workshop included four steps: (1) completion of a survey (2) advice from a retirement expert (3) extensive literature review and (4) multiple pre-workshop discuss...

Disclosure: P.F. Backeljauw: Advisory Board Member; Self; Ascendis Pharma, Inc., Novo Nordisk, BioMarin. Consulting Fee; Self; Ascendis Pharma, Inc., Novo Nordisk, BioMarin, Cavalry, Upsher-Smith. Speaker; Self; Ascendis Pharma, Inc., BioMarin. A.K. Maniatis: Advisory Board Member; Self; Alexion Pharmaceuticals, Inc., Ascendis Pharma, Inc., BioMari...

Sex chromosome aneuploidies (SCAs) are a family of genetic disorders that result from an atypical number of X and/or Y chromosomes. SCAs are the most common chromosomal abnormality, affecting ∼1/400 live births, yet are often underdiagnosed, leading to over-representation of more severely impacted individuals in many clinical studies. In addition t...

This study examined the validity of two automated methods (BAUSport, BoneXpert software using Fels, Greulich-Pyle, Tanner-Whithouse III protocols) for estimating skeletal age (SA) in young athletes in comparison to a reference standard (Fels). 85 male and female athletes, nine to seventeen years of age, from multiple sports were assessed for SA as...

Leptin deficiency in both mice and humans is characterized by a decrease in total lymphocytes, CD4+ helper T cell number increased thymocyte apoptosis, and a shift from the Th1 toward Th2 phenotype. ▪ These changes increase susceptibility to intracellular infections and correlate with several bacterial, viral, and parasitic infections. In undernour...

GH resistance and low IGF-I production appear to be adaptive mechanisms to preserve calories during malnutrition. ✓ Protein deficiency results in a state of GH resistance as well as a state of end-organ resistance to IGF-I. ✓ Zinc, magnesium, and vitamin B6 deficiencies that occur in many children, malnutrition has been associated with GH resistanc...

Adipose tissue plays a central role in regulating whole-body energy and glucose homeostasis through secreting hormones that regulate multiple functions at both organ and systemic levels. Low leptin levels have been documented in all studies of children with malnutrition (mild, moderate, and severe). ▪ During fasting, leptin levels fall rapidly befo...

During malnutrition, IGF1 deficiency and GH resistance can negatively affect the functions of the immune system (lymphocytes and cytokines) and predispose to infection and inflammation which further deteriorates growth and induce wasting.

Introduction The Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) created separate growth charts for girls and boys because growth patterns and rates differ between sexes. However, scenarios exist in which this dichotomizing “girls versus boys” approach may not be ideal, including the care of non-binary youth or...

Hypogonadism in adolescents is a clinical syndrome resulting from failure to produce physiological concentrations of sex steroid hormones with accompanying symptoms, such as slowed growth and delayed pubertal maturation. Hypogonadism may arise from gonadal disease (primary hypogonadism), dysfunction of the hypothalamic-pituitary axis (secondary hyp...

The overall incidence of sex chromosome aneuploidies is approximately 1 per 500 live-born infants, but far more common at conception. I shall review the fertility aspects of the sex chromosome trisomies, XXY, XYY, XXX, with special reference to the karyotype 45,X/47,XXX. Each has a "specific" (but variable) phenotype, but may be modified by mosaici...

Malnutrition remains an international concern because it represents a major cause of childhood morbidity and mortality. In infants and children malnutrition significant metabolic, hormonal, and immune changes to occur with short-and long-term effects and outcomes. Thus, studies which contribute to the prevention, amelioration, or rehabilitation of...

Objectives Intramuscular (IM) testosterone enanthate (TE) and testosterone pellets were FDA-approved prior to 1962 for pediatric use but not studied in controlled trials in adolescents. An analysis using non-linear mixed effect (NLME) modeling was designed to evaluate the adult pharmacokinetics (PK) of subcutaneous (SC) and IM TE. This model was us...

Growth hormone deficiency (GHD) is a clinical syndrome that can manifest either as isolated or associated with additional pituitary hormone deficiencies. Although diminished height velocity and short stature are useful and important clinical markers to consider testing for GHD in children, the signs and symptoms of GHD are not always so apparent in...

The 3rd International Workshop on Klinefelter Syndrome, Trisomy X, and 47,XYY syndrome was held in Leiden, the Netherlands, on September 12–14, 2022. Here, we review new data presented at the workshop and discuss scientific and clinical trajectories. We focus on shortcomings in knowledge and therefore point out future areas for research. We focus o...

The growth hormone (GH)–insulin-like growth factor (IGF) cascade is central to the regulation of growth and metabolism. This article focuses on the history of the components of the IGF system, with an emphasis on the peptide hormones, IGF-I and -II, their cell surface receptors, and the IGF binding proteins (IGFBPs) and IGFBP proteases that regulat...

Background: People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in classical art, as well as the courts of European monarchs, and were exploited in "shows." Serious medical evaluation began in the late 19th century with the description...

The Pediatric Endocrine Society (PES) was initially established in 1972 as the Lawson Wilkins Pediatric Endocrine Society (LWPES), by some of Wilkins' former fellows. As the society grew from its 37 founding members and Dr. Wilkins' influence faded, the name of the society was changed in 2010 and now counts about 1,500 members, mostly from the US a...

Gonadotropin-releasing hormone agonists (GnRHa's) are the standard treatment for children with central precocious puberty (CPP). We aim to present data on available GnRHa options with an easy-to-review table and discuss factors that influence treatment selection. Five GnRHa's are currently FDA-approved and prescribed in the US and published data su...

BACKGROUND Pediatric endocrine care is often performed by pediatricians in Central America and Caribbean countries due to limited number of pediatric endocrinologists. These health care providers are seldom members of endocrine societies and frequently lack formal training in pediatric endocrinology. OBJECTIVE To describe the scope of a virtual me...

Background: Pediatric endocrinology is a specialty that is struggling worldwide to maintain adequately trained professionals. Pediatric endocrine care in Central America and Caribbean countries is often performed by pediatricians or adult endocrinologists due to the limited number of pediatric endocrinologists. These health care providers are seld...

Primary (acute and chronic) malnutrition is still prevalent in developing countries because of inadequate nutrition and poor sanitation caused by social, economic, and environmental factors. In addition, acute malnutrition can occur secondary to an underlying disease that interferes with the intake, digestion, absorption, or assimilation of differe...

Since cystic fibrosis (CF) was first described in 1938, there have been many discoveries and innovations in the field, each having a profound impact on survival, growth and quality of life. For example, the introduction of enteric-coated pancreatic enzyme microspheres increased fat absorption and improved nutritional status. Early detection of CF t...

Insulin is the key anabolic hormone of metabolism, with clear effects on glycaemia. Near-complete insulin deficiency occurs in type 1 diabetes (T1D), the predominant form affecting children, and uniformly fatal until the discovery of insulin. By the early 20th century, it was known that T1D was caused by the lack of a factor from pancreatic islets,...

Twenty-one scientists met for this year’s virtual conference on Auxology held at the University Potsdam, Germany, to discuss child and adolescent growth during times of fear and emotional stress. Growth within the broad range of normal for age and sex is considered a sign of good general health whereas fear and emotional stress can lead to growth f...

Context Serum IGF-1 levels are relatively constant in somatropin-treated children with growth hormone deficiency (GHD), and guide dose adjustments for clinical efficacy and long-term safety. IGF-1 levels following treatment with long-acting growth hormones such as lonapegsomatropin (TransCon hGH), a once-weekly somatropin prodrug, exhibit a charact...

Objectives: Some idiopathic short stature (ISS) patients may have varying degrees of insulin-like growth factor 1 (IGFI) deficiency. Others with growth hormone deficiency (GHD) (peak GH < 7 ng/dL after provocation) have normal IGFI levels. Do children with ISS or those with GHD with variable pretreatment IGFI standard deviation score (IGFISDS) hav...

Since antiquity Man has been fascinated by the variations in human (and animal) growth. Stories and art abound about giants and little people. Modern genetics have solved some of etiologies at both extremes of growth. Serious study began with the pathophysiology of acromegaly followed by early attempts at treatment culminating in modern endoscopic...

Pubertal maturation is a time of dramatic physical, reproductive, and psychological changes, including the development of secondary sex characteristics and changes in body composition. It requires a complex series of hormonal changes initiated by alterations in hypothalamic regulatory mechanisms that are incompletely understood, culminating in gona...

Delayed puberty occurs when no signs of pubertal maturation are seen by 14 years of age in boys or 13 years in girls. Although constitutional delay of growth and puberty is commonly seen and is often regarded as benign, there are many other causes of pubertal delay that ultimately result in permanent hypogonadism, and these must be differentiated f...

Context There is no consensus on the effect of recombinant human growth hormone (rhGH) therapy on skeletal maturation in children despite the current practice of annual monitoring of skeletal maturation with bone age in children on rhGH therapy. Aims To investigate the effects of long-term rhGH therapy on skeletal age in children and explore the a...

Testosterone replacement therapy (TRT) is routinely prescribed in adolescent males with constitutional delay of growth and puberty (CDGP) or hypogonadism. With many new testosterone (T) formulations entering the market targeted for adults, we review current evidence and TRT options for adolescents and identify areas of unmet needs. We searched PubM...

Emotional deprivation can lead to growth faltering of infants and children. The mechanism(s) involved differ in that for infants, the major metabolic problem is inadequate energy intake for growth. In young children, it is likely that the emotional deprivation causes a syndrome not only of growth faltering, but with bizarre behaviors, especially wi...

Growth is the task of children. We review the normal process of linear growth from the fetus through adolescence and note that growth is the result of age- and gender-dependent interactions among key genetic, environmental, dietary, socioeconomic, developmental, behavioral, nutritional, metabolic, biochemical, and hormonal factors. We then define t...

Context We characterized linear growth in infants and children with X-linked hypophosphatemia (XLH). Objective Provide linear growth curves for children with XLH from birth to early adolescence. Design Data from four prior studies of XLH were pooled to construct growth curves. UX023-CL002 was an observational, retrospective chart review. Pre-trea...

Sex chromosome aneuploidies (SCA) are relatively common as a group, perhaps 1 per 500 births, but much more common at conception. Many syndromes have been noted in those with these conditions, but not so many data are available concerning the hypothalamic–pituitary–gonadal (HPG) axis. The physiology of the HPG axis is first reviewed at four epochs...

We provide an in-depth review of the role of androgens in male maturation and development from the fetal stage through adolescence into emerging adulthood and discuss the treatment of disorders of androgen production throughout these time periods. Testosterone, the primary androgen produced by males, has both anabolic and androgenic effects. Androg...

Success in sports is often defined by winning, which drives some athletes to use performance-enhancing drugs to gain an advantage over opponents. The use of doping agents in sports has a long history, especially over the last years, secondary to scandals and controversy. Athletes and the general public are now more aware and educated about this iss...

A variety of factors influence growth during adolescence, including genetics, hormones, nutrition, and timing and tempo of puberty. Many pubertal disorders result in abnormal patterns of growth; therefore, good understanding of pubertal maturation is essential. Although key pubertal events follow a fairly typical time course, there is significant i...

Background: In adolescents, testosterone may have several effects including promotion of secondary sexual characteristics and pubertal growth, attainment of optimal muscle mass and peak bone mass, optimization of the metabolic profile, and psychosocial maturation and well-being. Summary: Testosterone therapy is a cornerstone of the management of...

“Doping” is as old as the ancient Olympics (776 BC to 394 AD) when athletes used herbal medications, animal organs (organotherapy was common to cure diseases and to improve vitality), stimulants, and hallucinogenic mushrooms to improve athletic performance. We discuss the issues of proper medical use of prohibited drugs (therapeutic use exemption)...

Inter-individual differences in size, maturity status, function, and behavior among youth of the same chronological age (CA) have long been a concern in grouping for sport. Bio-banding is a recent attempt to accommodate maturity-associated variation among youth in sport. The historical basis of the concept of maturity-matching and its relevance to...

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary...

This update, written by authors designated by multiple pediatric endocrinology societies (see List of Participating Societies) from around the globe, concisely addresses topics related to changes in GnRHa usage in children and adolescents over the last decade. Topics related to the use of GnRHa in precocious puberty include diagnostic criteria, glo...

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Our objective was to assess the risk of adrenal insufficiency (AI) with short-term use of low- to moderate-potency topical corticosteroids (TCS) for treatment of atopic dermatitis. Our systematic literature search revealed 9 studies (n = 371) that evaluated AI using adrenocorticotropic hormone stimulation testing, with measures of serum cortisol le...

This report illustrates the links between history, sport, endocrinology, and genetics to show the ways in which historical context is key to understanding the current conversations and controversies about who may compete in the female category in elite sport. The International Association of Athletics Federations (IAAF) introduced hyperandrogenemia...

Context Clomiphene is a commonly abused performance-enhancing drug by males in sport, but the extent to which testosterone increases in healthy males following its use is unknown. Additionally, evidence has suggested that clomiphene, a mixture of cis- and trans-isomers zuclomiphene and enclomiphene, is detectable in urine for months following use;...

Doping is at least as old as the ancient Olympics. Substances taken to improve athletic performance ranged from stimulants to hallucinogenic plant substances, but more recently include anabolic agents. Recombinant human growth hormone, rhGH, is one agent with a relatively short history of use, but few data to unequivocally show that it actually imp...

Background/aims: A meta-analysis was performed to determine the likelihood of hypothalamic-pituitary-adrenal (HPA) axis suppression following short-term cutaneous treatment of atopic dermatitis with topical corticosteroids (TCS) in pediatric patients. Methods: All published pediatric clinical trials evaluating TCS use with pre- and post-treatmen...

Many neoplastic diseases that are common in childhood, adolescence and early adulthood were previously uniformly and swiftly fatal. These neoplastic diseases and their therapies are associated with an increased incidence of multiple endocrinopathies. For example, intracranial neoplasias invade the hypothalamus and/or pituitary and cause deficiencie...

Introduction: NATESTO®testosterone nasal gel (TNG) is a liquid gel that is applied in the nose for the treatment of male hypogonadism. There is a reasonable concern that administration of TNG to patients with active rhinitis could modify absorption. Results from two clinical studies are reported wherein subjects with allergic rhinitis (AR) subject...

Cushing’s syndrome is a rare disorder caused by prolonged exposure to high levels of cortisol. Cushing’s syndrome can be divided into exogenous (often iatrogenic) or endogenous [adrenocorticotropic hormone (ACTH)–dependent] categories. Approximately 10% of new diagnoses each year are in children. The most common pathophysiology of endogenous Cushin...

Small-for-gestational age (SGA) infants are at risk for short and long term medical and metabolic complications. Most SGA infants (85-90%) demonstrate spontaneous catch-up growth, typically in the first year after birth. Although catch-up growth (CUG) is a desired goal, it is important to note if CUG is too rapid the infants are at increased risk f...

We are writing this piece in the aftermath of the 2016 Olympic Games in Rio de Janeiro, Brazil. Each of the words in the title plays a role(s) in deciding who may compete, especially who may compete as a woman. We shall be careful to disentangle the issues of genes and gender from hormonal levels of the potent androgen testosterone, and very clearl...

Puberty is the state of physical maturation at which persons are first capable of reproduction. In practice, the notion is that puberty begins with the first external signs of adolescent development. In boys, this usually consists of testicular enlargement and scrotal thinning. Delayed puberty is, by concept, adolescent development that begins two...

Recombinant human growth hormone (rhGH) has been available since 1985. Before 1985 growth hormone (GH) was extracted from cadaveric pituitary glands, but this was stopped in most countries that year, following the recognition that it could transmit Creutzfeldt–Jacob disease. The primary goal of rhGH treatment in GHD patients is to normalize height...

Obesity is a major public health problem in the world with increasing prevalence among children and adolescents. The current study was a descriptive crosssectional study involving 1100 students attending public and private secondary schools in Lagos. Calculations of body mass index (BMI) were performed, and 513 males and 587 females aged between 10...

The most common isolated hormonal deficiency after traumatic brain injury (TBI) in both children and adults is growth hormone deficiency (GHD). Adequate evaluation of the growth hormone (GH) axis after TBI in children and adults is evolving. Despite the inherent limitations to this field of research, available data depict the importance of evaluati...

The impact of exercise training on the neuroendocrine control of the pituitary in the developing child is complex and the exact mechanisms are not fully understood. Multiple determinants influence adaptive hypothalamic-pituitary secretory responses to physical stress, namely, training intensity and duration, nutrition and energy balance, gender, ag...

Following the 1st International Workshop on the Klinefelter Syndrome in 2010 (Juul et al., 2011), the 2nd IWKS took place in Munster, Germany from March 10 to 12, 2016 and was organized by the Centre of Reproductive Medicine and Andrology of the University of Munster. During the program, talks were presented by leading researchers in the field foll...

Many men with conditions linked to azoospermia were formerly considered infertile. However, over the last two decades advances in assisted reproductive technology (ART) have been devised and have permitted these men to become biological fathers. Foremost among these have been testicular sperm extraction (TESE) and a “microdissection” advance in whi...

The body goes through remarkable changes from birth through childhood and adolescence into adulthood. Biological growth and maturation, along with behavioral development, are important aspects “growing up.” These three processes, growth, maturation, and development, dominate the daily lives of children and adolescents for approximately the first tw...

Advantages of testosterone nasal gel include ease of administration, low dose, and no risk of secondary transference. The efficacy and safety of testosterone nasal gel was evaluated in hypogonadal males. The ninety-day, randomized, open-label, dose-ranging study, included potential dose titration and sequential safety extensions to 1 year. At 39 US...

Klinefelter syndrome (KS) is the leading genetic cause of primary hypogonadism and infertility in men. The clinical phenotype has expanded beyond the original description of infertility, small testes, and gynecomastia. Animal models, epidemiologic studies, and clinical research of male subjects with KS throughout the lifespan have allowed the bette...

The search for talent is pervasive in youth sports. Selection/exclusion in many sports follows a maturity-related gradient largely during the interval of puberty and growth spurt. As such, there is emphasis on methods for assessing maturation. Commonly used methods for assessing status (skeletal age, secondary sex characteristics) and estimating ti...

Between 1968 and 1999, the International Olympic Committee (IOC) required all female athletes to undergo genetic testing as part of its sex verification policy, under the assumption that it needed to prevent men from impersonating women and competing in female-only events. After critics convinced officials that genetic testing was scientifically an...

To determine the role of endogenous opioid peptides in regulating pulsatile luteinizing hormone (LH) release in the early follicular phase of the menstrual cycle of eumenorrheic women, we evaluated serum LH concentrations in blood collected every 10 min for 12 h in 27 women each studied during two menstrual cycles: (1) without pretreatment and (2)...

In spite of the high prevalence of performance-enhancing drug (PED) use, media attention has focused almost entirely on PED use by elite athletes in order to illicitly gain a competitive advantage in sports, and not on the health risks of PEDs. There is a widespread misperception that PED use is safe or that adverse effects are manageable. In reali...

Titrating the dosage of growth hormone (GH) to serum levels of insulin-like growth factor-I (IGF-I) is a feasible treatment strategy in children with GH deficiency (GHD) and idiopathic short stature (ISS). The objective was to assess the dose-sparing effect and theoretical safety of IGF-I based GH therapy. This was a post-hoc analysis of previously...