Normal puberty
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Official reprint from UpToDate® www.uptodate.com ©2015 UpToDate®
Normal puberty Author Frank M Biro, MD
Section Editors Amy B Middleman, MD, MPH, MS Ed Teresa K Duryea, MD Peter J Snyder, MD Mitchell Geffner, MD
Deputy Editor Alison G Hoppin, MD
Disclosures: Frank M Biro, MD Nothing to disclose. Amy B Middleman, MD, MPH, MS Ed Grant/Research Support: Novartis [immunizations; developing student curricula]. Teresa K Duryea, MD Nothing to disclose. Peter J Snyder, MD Grant/Research/Clinical Trial Support: AbbVie [hypogonadism (Testosterone gel 1% and 1.62%)]; Novo Nordisk [GH deficiency (norditropin)]; Ipsen [Acromegaly
All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Feb 2015. | This topic last updated: Nov 05, 2013. INTRODUCTION — Adolescents experience several types of maturation, including cognitive (the development of formal operational thought), psychosocial (the stages of adolescence), and biological. The complex series of biological transitions are known as puberty, and these changes may impact psychosocial factors. The most visible changes during puberty are growth in stature and development of secondary sexual characteristics. Equally profound are changes in body composition; the achievement of fertility; and changes in most body systems, such as the neuroendocrine axis, bone size, and mineralization; and the cardiovascular system. As an example, puberty is associated with cardiovascular changes, including greater aerobic power reserve, electrocardiographic changes, and blood pressure changes. The normal sequence of pubertal events and perils of puberty are reviewed here. Precocious and delayed puberty are discussed separately. (See "Definition, etiology, and evaluation of precocious puberty" and "Diagnosis and treatment of delayed puberty".) DEFINITIONS — Puberty is the general term for biological maturation into sexual maturity. A number of other terms describe specific antecedents or components of puberty: ● Adrenarche is the activation of the adrenal cortex for the production of adrenal androgens, and typically occurs before the onset of puberty. This process is discussed in detail separately. (See "Normal adrenarche" and "Premature adrenarche".) ● Gonadarche is the activation of the gonads by the pituitary hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH) ● Pubarche is the appearance of pubic hair ● Thelarche is the appearance of breast tissue ● Menarche is the age of onset of the first menstrual period ● Spermarche is the age at first ejaculation (heralded by nocturnal sperm emissions and appearance of sperm in the urine) [1] Precocious puberty is usually defined as the onset of secondary sexual development before the age of eight years in girls and nine years in boys. These limits are chosen to be 2.5 to 3 standard deviations (SD) below the mean age of onset of puberty. (See "Definition, etiology, and evaluation of precocious puberty".) Delayed puberty is defined as the absence or incomplete development of secondary sexual characteristics by an age at
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which 95 percent of children of that sex and culture have initiated sexual maturation. In the United States this corresponds to an upper limit of 12 years for girls (breast development), and of 14 years for boys (for testicular enlargement). (See "Diagnosis and treatment of delayed puberty".) PUBERTAL CHANGES Sexual maturity rating (Tanner stages) — Puberty consists of a series of predictable events that usually proceed in a predictable pattern, with some variation in timing of onset, sequence, and tempo (figure 1A-B). The staging system utilized most frequently is that of sexual maturity ratings (SMR). These are also known as "Tanner stages" because they were initially published by Marshall and Tanner [2,3]. These consist of systematized descriptions of the development of secondary sexual characteristics, consisting of breast changes in females, pubic hair changes in both males and females, and genital changes in males. SMR for pubic hair, breast, and genitalia consists of five categories, with stage one representing prepuberty and stage five representing adult development (table 1). The stages are illustrated by the figure in boys (picture 1) and in girls (picture 2A-B). In girls, estrogen stimulation of the vaginal mucosa causes a physiologic leukorrhea, which is a thin white non foul-smelling vaginal discharge that typically begins 6 to 12 months before menarche. (See "The pediatric physical examination: The perineum", section on 'Preadolescent and adolescent females'.) As is discussed below, the timing of pubertal maturation has an important influence on self-esteem, behavior, growth, and weight. As an example, early maturation is associated with slightly shorter adult stature [4,5] and with greater adult ponderosity and adiposity [5,6]. Details of the physiological changes expected during puberty are discussed below. (See 'Sequence of pubertal maturation' below.) Growth spurt — Approximately 17 to 18 percent of adult height accrues during puberty [7]. The timing of the growth spurt (peak height velocity) varies by gender, occurring approximately two years earlier in girls than in boys. In girls, peak height velocity occurs, on average, 0.5 years prior to menarche [8]. The increase in height affects both axial (trunk) and appendicular (limbs) components [9]. The limbs accelerate before the trunk, with the distal portions of the limbs accelerating before the proximal portions; thus, the adolescent in early puberty is "all hands and feet." In later puberty, however, the growth spurt is primarily truncal [9]. Height velocity can be plotted and compared with norms using height velocity growth charts. The most commonly used charts are those published by Tanner and Davies (figure 1A-B) [10]. Although these are used for longitudinal tracking and acknowledge the variation between early, average and late maturers, their accuracy is limited because they were prepared from cross-sectional rather than longitudinal data. Other growth charts were generated from longitudinal data, such as the series of charts published by the Harvard Six-Cities study, but are less widely available [11]. The disparity in mean adult height of men and women results from the timing and peak of the growth spurt in boys and girls. On average, boys are 2 cm taller at the age girls begin their peak height velocity and continue to accrue 3 to 4 cm per year for an additional one to two years, until they enter puberty. Boys experience a greater peak height velocity than do girls (10.3 versus 9.0 cm/year) (figure 2A-B). When calculated over a 12-month span rather than a shorter period of peak growth, these values fall to 9.5 and 8.3 cm, respectively. When evaluating growth, the clinician should look at whole-year changes because of seasonal variability; greater growth typically occurs in spring, although the time of year may vary when a given individual has a seasonal peak. Extremely early onset of puberty (precocious puberty) and earlier peak height velocity is associated with reduced adult height, due to early epiphyseal closure (see "Treatment of precocious puberty", section on 'Decision to treat'). Whether pubertal onset that is early but within the normal range is associated with reduced adult stature is less clear. In girls, early menarche was associated with greater peak height velocity but shorter adult stature, while early thelarche had no effect on adult stature [12]. In boys, those who mature relatively early but within the normal range have a modest reduction in adult height [13]. The diminished adult height is attributable to shorter leg length; sitting height is not reduced. Body weight appears to influence these results: in the same study, boys who were underweight during childhood tended to have longer leg length and no change in adult height. It is probably not appropriate to extrapolate these results to girls, because obesity is sometimes associated with earlier onset of puberty in girls, and obesity may have the opposite effect in boys. (See http://www.uptodate.com/contents/normal-puberty?source=search_result&search=PUBERTAD&selectedTitle=1%7E150
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"Comorbidities and complications of obesity in children and adolescents", section on 'Growth and puberty'.) Bone growth — Bone growth accelerates during puberty, in concert with height velocity, but bone mineralization lags behind. As examples, bone mineralization peaks around the age of menarche in girls, which occurs approximately 9 to 12 months later than peak height velocity [14,15]. Bone growth occurs first in length, followed by width, then mineral content, then bone density [16]. The disparity in the timing of bone growth and mineralization may place the growing adolescent at increased risk for fracture. (See 'Musculoskeletal injuries' below.) Of total body calcium, approximately one-half is laid down during puberty in females, and one-half to two-thirds in males [16,17]; by the end of puberty, males have nearly 50 percent more total body calcium than do females. The increase in bone density during puberty is greater in African-American females than in Caucasian females [18]. The risk for osteoporosis during adulthood may be related to both specific "insults" and the timing of factors impacting bone deposition during puberty [9]. These data suggest that the window of opportunity to maximize peak bone mass may be limited [16]. (See "Prevention of osteoporosis", section on 'Maximizing peak bone mass'.) Weight and body composition — Puberty is associated with significant changes in body weight and alterations in body composition, especially in lean body mass and the proportion of body fat (adiposity), with different patterns in girls as compared with boys. Growth curves for Body Mass Index (BMI) describe the typical increase in body mass that occurs during puberty (figure 3A-B), but do not reflect the differences between early-maturing and late-maturing children, nor do they distinguish between changes in lean body mass versus adipose tissue. In early puberty, the annual increase in BMI is driven primarily by changes in lean body mass. Later, the increase in BMI tends to be driven by increases in fat mass [19]. This general pattern diverges between the genders: boys tend to have a decrease in body fat in early puberty, and then proceed to a substantial increase in lean body mass. Girls tend to have a higher proportion of fat mass than boys at each phase, and after 16 years of age, the annual increase in BMI is largely because of increases in fat mass [19,20]. These general patterns are altered by the individual’s nutritional status; either boys or girls may experience an ongoing increase in body fat, regardless of gender or pubertal stage, reflecting developing or worsening obesity. Obesity tracks from adolescence to adulthood, and earlier onset of obesity is associated with increased cardiovascular morbidity and mortality [21-23]. (See "Clinical evaluation of the obese child and adolescent".) SEQUENCE OF PUBERTAL MATURATION — Some variability occurs in a given individual's timing, sequence, or tempo of pubertal maturation. However, most adolescents follow a predictable path through pubertal maturation. Girls — The earliest secondary sexual characteristic in most girls is breast/areolar development (thelarche) (picture 2A), although a substantial minority have pubic hair as the initial manifestation (pubarche) (picture 2B) [24]. Maternal preeclampsia increased threefold the likelihood of pubarche as the initial manifestation of puberty; the likelihood was directly related to the severity of preeclampsia [25,26]. Menarche occurs, on average, 2.6 years after the onset of puberty (figure 1A) [2,8,15]. The initial manifestation predicts body morphology and composition throughout pubertal maturation into early adulthood. As an example, girls with breast development as the initial manifestation of puberty have both an earlier age of menarche and greater body mass index (BMI) throughout puberty and as adults [27]. When menarche occurs before the individual reaches the age of 12 years, it is associated with increases in weight and BMI [28-30]. In addition, girls who mature early are at an increased risk for obesity when compared with late maturers [6]. Boys — The earliest stage of male maturation, which has a mean duration of six months, is an increase in testicular volume (figure 4). Almost all boys have an increase in testicular volume (≥3 mL) prior to the appearance of penile growth and pubic hair (picture 1) [24,31]. Thus, if one considers only pubic hair in the assessment of early male puberty, misclassification and unnecessary testing may result. The appearance of sperm in the urine and the onset of nocturnal sperm emissions occur shortly after the attainment of peak height velocity; many consider these events the male equivalent of menarche (figure 1B). Testicular volume is typically measured using the Prader orchidometer, a series of three-dimensional ellipsoids with a http://www.uptodate.com/contents/normal-puberty?source=search_result&search=PUBERTAD&selectedTitle=1%7E150
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volume from 1 to 25 mL or more. Penile length is measured from the pubic ramus to the tip of the glans while compressing the suprapubic fat pad and applying gentle traction. Mean stretched penile stretch length (measured from the pubis symphysis to the tip of the non-erect penis excluding foreskin) is approximately 3.75 cm (± 0.54 cm) at 1 year of age and gradually increases to 4.84 cm by late childhood, then increases sharply to about 9.5 cm (± 1.12 cm) by late puberty (according to measurements from a predominantly white population) [32]. This measurement is rarely used for monitoring of pubertal progress. In some clinical contexts (eg, when one is concerned about endogenous or exogenous androgens), it is helpful to consider whether a given testicular volume is appropriate for a pubic hair stage. The following figure allows the clinician to evaluate the relationship between testicular volume and pubic hair (figure 4) [31]. TIMING OF PUBERTAL ONSET — The mean age of onset of puberty is about 10.5 years of age in girls and 11.5 years in boys. The normal range for pubertal onset is between 8 and 12 years in girls, and 9 to 14 years in boys. (See 'Definitions' above.) Trends in pubertal timing — Pubertal onset in girls has been trending earlier in the United States and in most other developed countries, as illustrated by the following observations: ● The average age of menarche in the United States declined from 12.53 to 12.34 years (a decline of 2.3 months) between the late 1980s and the early 2000s [33]. In addition, there was an overall decline of 4.9 months since the 1960s through the early 2000s [33,34]. In non-Hispanic White girls, the age of menarche decreased from 12.57 to 12.52 years, non-Hispanic Blacks 12.09 to 12.06 years, and for Mexican Americans 12.23 to 12.09. Changes in the population distribution of race/ethnicity and anthropometric changes in body weight and height may, in part, explain the larger change seen in the overall group compared with changes within each ethnic group. ● In a 1997 study from the United States and Puerto Rico, the mean ages for the onset of breast development were 8.9 years in African-American girls and 8.8 years in white girls; the mean age for pubic hair growth was 10.0 years in African-American girls and 10.5 years in White girls (figure 5) [35]. In this study, the earliest signs of puberty were at ages considerably younger than had been reported previously, and striking racial differences in timing were found. Pubertal onset in boys also appears to be occurring earlier in the United States. In a study including more than 4000 healthy boys, the mean age for entering puberty (SMR for genital development stage 2) was 10.14 years for white boys, 10.04 years for Hispanic boys, and 9.14 years for African American boys [36]. These thresholds are 1.5 to 2 years earlier than historical norms. Similar trends have been reported from several European and Scandinavian countries and China [37-41]. The relationship between pubertal onset and obesity in boys is not clear. Some studies suggest that being overweight or obese is associated with later onset of puberty in boys, in contrast to findings in girls [31,42-44]. Conversely, other studies report that increased body mass index (BMI) and fat mass is associated with earlier puberty in boys, similar to findings in girls [36,37,45,46]. However, several studies are inconclusive or demonstrate no relationship [28,47]. The earlier onset of puberty has had important implications for the diagnosis of precocious puberty. Precocious puberty usually has been defined as pubertal onset prior to eight years of age in girls and nine years in boys. Because of the earlier onset of puberty in the United States, it has been suggested that a threshold of seven years in White girls, and six years in African-American girls be used as a threshold for evaluation for precocious puberty [4]. Following these suggestions may lead to under-diagnosis of endocrine disorders, the appropriate threshold for evaluation remains controversial and probably varies among populations [48]. (See "Definition, etiology, and evaluation of precocious puberty".) Determinants of pubertal timing — Genetics accounts for the majority of the variability in the timing of pubertal onset. The timing of puberty and menarche in a girl is best predicted by the timing of menarche in her mother. Other factors that influence pubertal onset include overall health, social environment (such as family stress or the presence of an adult nonbiologically-related male) [49-51], and possibly environmental exposures, such as endocrine disruptors (environmental contaminants that may affect endocrine processes) [52]. Studies have suggested an interaction between genetics and the environment. As an example, age of menarche decreased to a greater extent in Black girls as compared with White girls from the 1970s to the 1990s [53]. The influence of environmental factors, including endocrine disruptors, on timing of http://www.uptodate.com/contents/normal-puberty?source=search_result&search=PUBERTAD&selectedTitle=1%7E150
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pubertal maturation is a subject of active research [54]. (See 'Trends in pubertal timing' above.) Pubertal timing varies substantially between race/ethnic groups. In a 2001 study in the United States, the rates of early maturation (menarche ≤11 years) were 7.8 percent for White, 12.3 percent for Black, 13.6 percent for Hispanic, and 5.2 percent for Asian girls [55]. The frequency of late maturation (menarche ≥14 years) ranged from 15.2 percent among White girls to 27 percent among Asian girls. This relationship appears to be primarily mediated by differences in rates of overweight; within each race/ethnic group, early maturing girls were approximately twice as likely to be overweight as compared with those maturing at an average age. The data in this study did not establish whether the relationship between age of menarche and obesity varies among racial and ethnic groups. (See 'Body fat and leptin' below.) Genetic contributors — Common genetic variants have been identified that appear to be associated with variation in age at menarche. In a meta-analysis of 32 genome-wide association studies that included more than 85,000 women, 32 common variants or single nucleotide polymorphisms (SNPs) associated with age at menarche were identified [56]. One of the genes in the 6q21 region, LIN28B, has emerged as an important candidate for mediating variation in age at menarche. Genetic variation in this region was also associated with age at menarche in several different human populations and was analyzed in a meta-analysis [57,58]. A study employing direct genotyping of LIN28B confirmed that variations in a particular region of this gene were associated with earlier puberty in both boys and girls [59]. LIN28B is a regulator of microRNA processing involved in developmental timing in C. elegans; a common variant in this gene was previously associated with reduced adult height. A few other genetic variants associated with adult height also were associated with age at menarche [56-58]. These observations suggest a genetic basis for previously observed associations between age at menarche and height; in some cases, this association might be mediated by earlier epiphyseal closure caused by earlier exposure to estrogens. Similarly, several genes that are associated with childhood obesity, including FTO (fat mass and obesity associated gene), SEC16B, TRA2B, TMEM18, and NEGR1 (neuronal growth regulator 1), were also associated with earlier age at menarche [56,57]. (See "Pathogenesis of obesity", section on 'Common obesity'.) One of the studies cited above also identified genetic variants associated with age at natural menopause [60]. (See "Ovarian development and failure (menopause) in normal women", section on 'Genetics' and "Clinical manifestations and diagnosis of menopause".) The GPR54 gene on chromosome 19p13.3, which encodes a G-protein coupled receptor, appears to have an important role in the initiation of puberty via its effect on hypothalamic GnRH [61]. Its ligand, kisspeptin, appears to modulate the negative feedback on GnRH secretion exerted by sex steroids. Loss-of-function mutations in GPR54 cause autosomal recessive idiopathic hypogonadotropic hypogonadism in humans and in a GPR54 knockout mouse model. Conversely, gain-of-function mutations in the GPR54 gene are associated with a form of central precocious puberty [62]. Thus, the GPR54-kisspeptin complex, appears to be an important gatekeeper for the onset of puberty and normal reproductive function. (See "Congenital gonadotropin-releasing hormone deficiency (idiopathic hypogonadotropic hypogonadism)".) Body fat and leptin — It has been proposed that a critical body weight [63] or body composition [64] is the most salient issue in the development and maintenance of pubertal events [28,63-65]. However, body weight alone probably is not a sufficient explanation. The overall earlier onset of puberty among the general population has been attributed to the increasing prevalence of obesity. (See 'Trends in pubertal timing' above.) Leptin has been proposed as the hormone responsible for the initiation and progression of puberty. Leptin is produced largely in adipocytes; large fat cells produce more leptin than do small ones, and serum leptin concentrations are highly correlated with body fat content. The potential importance of leptin is illustrated by the observation that mice deficient in leptin fail to undergo pubertal development, whereas the administration of leptin to such animals results in pubertal onset [66]. Furthermore, higher serum leptin concentrations in girls are associated with increased body fat and an earlier onset of puberty [67]. In this study, a 1 ng/mL increase in serum leptin lowered the age at menarche by one month, and a gain in
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body fat of 1 kg lowered the timing of menarche by 13 days. (See "Physiology of leptin".) Leptin appears to be one of several factors that influence the maturation of the gonadotropin-releasing hormone (GnRH) pulse generator, probably as a signal of the availability of metabolic fuel [68]. Serum leptin concentrations increase immediately before puberty in both genders but differ after the initiation of puberty. In males, serum leptin falls after the onset of puberty, returning to baseline 30 to 40 months later [69]. In females, leptin values rise throughout puberty and may be influenced by many factors. In one study, leptin values in pubertal girls were correlated with the sum of skinfolds (abdominal subcutaneous more than abdominal visceral more than peripheral subcutaneous fat), as well as serum free testosterone and free estrogen; these three factors accounted for 74 percent of the variance in leptin levels [70]. PERILS OF PUBERTY — Puberty is associated with a number of complications that present challenges to the patient and family. These "perils of puberty" include anemia, gynecomastia, acne, psychological correlates of puberty, certain types of sports-related injuries, myopia, scoliosis, and dysfunctional uterine bleeding. Anemia — Anemia and iron deficiency are common among adolescent girls as compared with adolescent boys or to school-aged children. The Third National Health and Nutrition Examination Survey (NHANES III) found a 9 percent incidence of iron deficiency and a 2 percent incidence of anemia among American girls between the ages of 12 and 15 years; the respective values were less than 2 percent for boys in this age group (table 2) [71]. Hemoglobin and serum ferritin concentrations increase with advancing pubertal stage in males, but not in females [72,73]. The gender differences are thought to result from biological differences (perhaps androgens), in addition to menstrual bleeding and insufficient iron intake in girls [73]. (See "Iron requirements and iron deficiency in adolescents".) Gynecomastia — Pubertal gynecomastia (in contrast to neonatal or senescence gynecomastia) occurs in approximately one-half of teenage boys at an average age of 13 years, and it persists for 6 to 18 months [74]. Boys with persistent gynecomastia (ie, lasting two years or more) have a diameter of palpable tissue ≥2 cm during the first year (odds ratio 8.7) [75]. Although the underlying diagnosis usually is "idiopathic pubertal gynecomastia," a variety of other etiologies including drugs, hypogonadism, testicular tumors, and hyperthyroidism, must be considered. The underlying mechanisms presumably reflect an imbalance in the effective estrogenic-to-androgenic stimulation, because of an increase in the production or action of estrogens or estrogen-like agents, a decrease in the production or action of androgens, or enhanced breast tissue sensitivity to these hormones [75]. (See "Epidemiology, pathophysiology, and causes of gynecomastia" and "Clinical features, diagnosis, and evaluation of gynecomastia".) Acne — Acne, a disorder of the pilosebaceous unit, is characterized by follicular occlusion and inflammation caused by androgenic stimulation. If the opening of the comedone is widely dilated, oxidation of keratinous material leads to the development of a blackhead without inflammatory acne. With a small opening, a closed comedo (whitehead) forms and may lead to inflammatory acne if the comedo ruptures into the dermis. With pubertal maturation in both boys and girls, the number of acne lesions increases, with a greater number of comedones than inflammatory lesions at all stages [76]. In girls, the severity of acne in later puberty is associated with higher serum levels of dehydroepiandrosterone sulfate (DHEAS) and a greater number of acne lesions in early puberty [77]. Although acne is common during puberty, moderate or severe acne in early puberty, usually with other signs of androgen excess, should alert the clinician to the possibility of an endocrinologic disorder, such as non-classical congenital adrenal hyperplasia. (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris".) Psychological changes — Pubertal maturation has an impact on psychological and social issues [78]. Puberty does not affect cognitive development [79], although the timing of pubertal maturation may affect psychosocial functioning. Prior to adolescence, no gender differences in depression occur; during adolescence, however, the prevalence of depression is twice as great in girls compared with boys [80]. As puberty progresses, boys develop a more positive selfimage and mood. By contrast, girls tend to become less satisfied with their physical appearance, and this tendency is more pronounced in Caucasian as compared with African-American girls. Caucasian girls also exhibit diminished self-worth as they pass from early to mid-adolescence [81]. Pubertal development may have an especially negative impact when a lack of synchrony between the timing of pubertal http://www.uptodate.com/contents/normal-puberty?source=search_result&search=PUBERTAD&selectedTitle=1%7E150
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development and chronologic age exists. For example, the early-maturing girl may experience a greater decrease in selfesteem and body satisfaction when compared with on-time or late-maturing girls [82]. In a large cross-sectional study, girls who were early-maturing and boys who were late-maturing were more likely to have psychopathology. Girls who matured early were more likely to have a lifetime history of disruptive behavior (attention-deficit, hyperactivity, oppositional, or conduct disorders) and suicide attempts, whereas boys who were late-maturing were more likely to have internalizing behaviors and emotional reliance on others [83]. Girls with early maturation are more likely to have older friends [84] and to be more vulnerable to peer pressures [85]. Certain cognitive characteristics have long been observed in adolescents, in which they make very different decisions when under the influence of strong emotions ("hot" cognition) as compared with decisions made under conditions of low emotional arousal ("cool" cognition) [86]. Recent observations suggest that adolescents display these cognitive characteristics because the dorsolateral prefrontal cortex, an area of the brain involved in impulse control, matures later than the remainder of the brain [87]. Thus, in times of stress, the brain of the adolescent may be less able to modulate the affective component as compared with adults. Musculoskeletal injuries — Pubertal status may help predict the specific type of musculoskeletal injuries that adolescents may encounter during participation in sports [88]. The greatest risk of damage to epiphyseal growth plates occurs during periods of peak height velocity, which also is the time of greatest change in bone mineral content [14] (see 'Bone growth' above). The asynchronous growth of body parts may result in a limited range of motion of some joints; when combined with the increase in muscle mass that occurs shortly after peak height velocity, the limited range of motion may lead to sprains or strains. (See 'Growth spurt' above.) A common overuse injury in teens is Osgood-Schlatter disease, which is an inflammation of the tibial tubercle apophysis. Not surprisingly, the age of peak incidence of distal radius fractures matches the age of peak height velocity in both boys and girls [89]. (See "Osgood-Schlatter disease (tibial tuberosity avulsion)".) Gynecologic consequences — Once a girl reaches menarche, rapid maturation of the reproductive axis ensues. By one year after menarche, 65 percent of girls have regular menstrual cycles, with 10 or more periods per year [90]. Girls with later onset of menarche progress more slowly to regular ovulatory cycles; when menarche occurs after the age of 13, only one-half will ovulate regularly within 4.5 years [91]. Dysfunctional uterine bleeding (DUB) refers to excessive, prolonged, and/or irregular endometrial bleeding. In adolescents, anovulation accounts for approximately 80 percent of cases of DUB. With anovulatory cycles, unopposed estrogen stimulates the endometrium, leading to a sustained proliferative phase rather than maturing to a secretory endometrium. Estrogen levels ultimately cannot sustain the hyperplastic endometrial lining, leading to irregular, sometimes heavy, menstrual bleeding. (See "Abnormal uterine bleeding in adolescents: Definition and evaluation", section on 'Abnormal uterine bleeding (AUB) in adolescents' and "Abnormal uterine bleeding in adolescents: Management".) Myopia — The greatest incidence of myopia occurs during puberty and is caused by growth in the axial diameter of the eye [92]. (See "Refractive errors in children", section on 'Refractive errors'.) Scoliosis — Accelerated progression of the degree of scoliosis occurs during puberty because of growth in the axial skeleton. (See "Adolescent idiopathic scoliosis: Clinical features, evaluation, and diagnosis", section on 'Natural history'.) Sexually transmitted disease — Sexually active adolescents represent the highest-risk age group for nearly all sexually transmitted diseases [93]. Both behavioral and biological factors are important. (See "Adolescent sexuality", section on 'Adolescent development' and "Sexually transmitted diseases: Overview of issues specific to adolescents", section on 'Epidemiology'.) Behavioral issues that increase risk for sexually transmitted diseases include younger age at onset of intercourse, the number of lifetime partners, and the perceived prevalence of sexually transmitted infections [94]. Biological factors include age of menarche (which influences behavioral factors) and gynecologic maturation. In the first year or two after menarche, a persistence of both columnar epithelial cells on the exocervix (cervical ectopy) and the http://www.uptodate.com/contents/normal-puberty?source=search_result&search=PUBERTAD&selectedTitle=1%7E150
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transformation zone of columnar to squamous epithelial cells on the exocervix occur. These factors may enhance infection with Chlamydia [95] and genital human papillomavirus [96,97]. INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.) ● Basics topics (see "Patient information: Normal sexual development (puberty) (The Basics)" and "Patient information: Early puberty (The Basics)" and "Patient information: Late puberty (The Basics)") SUMMARY — Puberty consists of a series of predictable events that usually proceed in a predictable pattern, with some variation in timing of onset, sequence, and tempo. ● The mean age for the first signs of puberty is about 10.5 years of age in girls, with a range from 8 to 12 years, In boys, the mean age of pubertal onset is 11.5 years, with a range from 9 to 14 years. Precocious puberty is usually defined as the onset of secondary sexual development before the age of eight years in girls and nine years in boys. (See 'Timing of pubertal onset' above.) ● Sexual maturity ratings (Tanner stages) for pubic hair, breast, and genitalia consists of five categories, with stage one representing prepuberty and stage five representing adult development (table 1). These stages are illustrated by the figure in boys (picture 1) and in girls (picture 2A-B). (See 'Sexual maturity rating (Tanner stages)' above.) ● The timing of the growth spurt (peak height velocity) occurs approximately two years earlier in girls than in boys (figure 1A-B). Extremely early onset of puberty (precocious puberty) and earlier peak height velocity is associated with reduced adult height, due to early epiphyseal closure. Whether pubertal onset that is early but within the normal range is associated with reduced adult stature is less clear. (See 'Growth spurt' above.) ● In most girls, the earliest secondary sexual characteristic is breast/areolar development (thelarche) (picture 2A), although a substantial minority have pubic hair as the initial manifestation (picture 2B). Menarche occurs, on average, 2.6 years after the onset of puberty and 0.5 years after peak height velocity (figure 1A). (See 'Girls' above.) ● In boys, the earliest stage of maturation is an increase in testicular volume, followed by penile growth and the appearance of pubic hair (picture 1). The appearance of sperm in the urine and the onset of nocturnal sperm emissions occur shortly after the attainment of peak height velocity; many consider these events the male equivalent of menarche (figure 1B). (See 'Boys' above.) ● In the United States and most other developed countries, the average age of onset of puberty has declined during the past four decades. Between 5 and 12 percent of girls have menarche younger than 11 years of age; this rate varies by race/ethnic group and weight status. (See 'Trends in pubertal timing' above.) ● The age at onset of puberty and the age of menarche are influenced by several factors. Genetics accounts for the majority of the variability; other factors include overall health, body weight, and possibly environmental exposures, such as endocrine disruptors. (See 'Body fat and leptin' above and 'Genetic contributors' above.) ● Typical thresholds for evaluating children for precocious puberty are signs of pubertal development before age eight years in girls and nine years in boys. Given the increasing frequency of earlier pubertal onset, some authorities suggest that these thresholds are too high. (See 'Trends in pubertal timing' above.)
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Normal puberty
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● Puberty is associated with a variety of physiologic changes which may come to medical attention, including acne and scoliosis, gynecomastia in boys, and anemia and dysfunctional uterine bleeding in girls. Psychological and emotional changes are common, with increased rates of depression and risk-taking behaviors. (See 'Perils of puberty' above.) Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Laron Z. Age at first ejaculation (spermarche)--the overlooked milestone in male development. Pediatr Endocrinol Rev 2010; 7:256. 2. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969; 44:291. 3. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970; 45:13. 4. Kaplowitz PB, Oberfield SE. Reexamination of the age limit for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment. Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society. Pediatrics 1999; 104:936. 5. Biro FM, McMahon RP, Striegel-Moore R, et al. Impact of timing of pubertal maturation on growth in black and white female adolescents: The National Heart, Lung, and Blood Institute Growth and Health Study. J Pediatr 2001; 138:636. 6. Garn SM, LaVelle M, Rosenberg KR, Hawthorne VM. Maturational timing as a factor in female fatness and obesity. Am J Clin Nutr 1986; 43:879. 7. Abbassi V. Growth and normal puberty. Pediatrics 1998; 102:507. 8. Biro FM, Huang B, Crawford PB, et al. Pubertal correlates in black and white girls. J Pediatr 2006; 148:234. 9. Bass S, Delmas PD, Pearce G, et al. The differing tempo of growth in bone size, mass, and density in girls is regionspecific. J Clin Invest 1999; 104:795. 10. Tanner JM, Davies PS. Clinical longitudinal standards for height and height velocity for North American children. J Pediatr 1985; 107:317. 11. Berkey CS, Dockery DW, Wang X, et al. Longitudinal height velocity standards for U.S. adolescents. Stat Med 1993; 12:403. 12. Huang B, Biro FM, Dorn LD. Determination of relative timing of pubertal maturation through ordinal logistic modeling: evaluation of growth and timing parameters. J Adolesc Health 2009; 45:383. 13. Lorentzon M, Norjavaara E, Kindblom JM. Pubertal timing predicts leg length and childhood body mass index predicts sitting height in young adult men. J Pediatr 2011; 158:452. 14. McKay HA, Bailey DA, Mirwald RL, et al. Peak bone mineral accrual and age at menarche in adolescent girls: a 6year longitudinal study. J Pediatr 1998; 133:682. 15. Taranger J, Engström I, Lichtenstein H, Svennberg- Redegren I. VI. Somatic pubertal development. Acta Paediatr Scand Suppl 1976; :121. 16. Magarey AM, Boulton TJ, Chatterton BE, et al. Bone growth from 11 to 17 years: relationship to growth, gender and changes with pubertal status including timing of menarche. Acta Paediatr 1999; 88:139. 17. Lloyd T, Rollings N, Andon MB, et al. Determinants of bone density in young women. I. Relationships among pubertal development, total body bone mass, and total body bone density in premenarchal females. J Clin Endocrinol Metab 1992; 75:383. 18. Gilsanz V, Roe TF, Mora S, et al. Changes in vertebral bone density in black girls and white girls during childhood and puberty. N Engl J Med 1991; 325:1597. 19. Maynard LM, Wisemandle W, Roche AF, et al. Childhood body composition in relation to body mass index. Pediatrics 2001; 107:344. 20. Gasser T, Ziegler P, Kneip A, et al. The dynamics of growth of weight, circumferences and skinfolds in distance, velocity and acceleration. Ann Hum Biol 1993; 20:239. 21. Tirosh A, Shai I, Afek A, et al. Adolescent BMI trajectory and risk of diabetes versus coronary disease. N Engl J Med 2011; 364:1315. http://www.uptodate.com/contents/normal-puberty?source=search_result&search=PUBERTAD&selectedTitle=1%7E150
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