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Delayed puberty is a relatively common occurrence in the pediatric population and is a common reason for referral to a pediatric endocrinologist. Although it is often benign, potentially serious causes should be considered and excluded when clinically indicated. This activity reviews the evaluation and management of pubertal delay, highlighting the role of interprofessional team members in collaborating to provide well-coordinated care to patients with this condition. Objectives: Identify the underlying etiology of delayed puberty in a child. Assess children with delayed puberty by integrating historical data, physical examination findings, and laboratory results. Apply evidence-based best practices for managing delayed puberty. Collaborate with interprofessional team members, including endocrinologists, pediatric endocrinologists, radiologists, medical geneticists, and pharmacists, to deliver comprehensive and coordinated care for patients with delayed puberty. Access free multiple choice questions on this topic.

Puberty is a period of significant physical and emotional changes, during which a child undergoes substantial hormonal and physiological alterations and develops the capacity to reproduce. The re-emergence of pulsatile gonadotropin-releasing hormone (GnRH) signaling from the hypothalamus is the initial event that triggers normal puberty. This process increases the pituitary secretion of gonadotropins—specifically luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In turn, these hormones stimulate the gonads to secrete sex hormones—testosterone in males and estrogen in females. These sex hormones are responsible for the physical signs of puberty; in females, the first sign of true puberty is breast development (thelarche), whereas in males it is testicular enlargement (testicular volume ≥4 mL or testicular length >2.5 cm). Thus, this sequential activation of the hypothalamic-pituitary-gonadal axis is the hallmark of true puberty.[1] Delayed puberty is defined as the absence of the expected clinical signs at an age at least 2 SDs later than the population mean. Traditional age cutoffs for diagnosing delayed puberty are 13 years for girls and 14 years for boys.[2][3] Importantly, pubic hair development is not a sign of puberty onset, as it may result from adrenal androgen production (adrenarche). Adrenarche is independent of the hypothalamic-pituitary-gonadal axis. Therefore, a child may display signs of adrenarche but still have a diagnosis of pubertal delay.[4]

Delayed puberty is defined as the absence of the expected clinical signs at an age at least 2 SDs later than the population mean. Traditional age cutoffs for diagnosing delayed puberty are 13 years for girls and 14 years for boys.[2][3] Importantly, pubic hair development is not a sign of puberty onset, as it may result from adrenal androgen production (adrenarche). Adrenarche is independent of the hypothalamic-pituitary-gonadal axis. Therefore, a child may display signs of adrenarche but still have a diagnosis of pubertal delay.[4] In girls, delayed puberty is characterized by the absence of breast development by age 13, a delay of more than 5 years (or 4 years according to some authors) between thelarche and menarche, or the absence of menarche by age 16 (15 according to some experts). In boys, pubertal delay is evident by a lack of testicular enlargement by age 14 or by a delay of 4 to 5 years or more between testicular enlargement and completion of puberty. Stalled or arrested puberty refers to a delay in pubertal progression after pubertal onset. In boys, once puberty has begun, a period of 3.2 ± 1.8 years (mean ± SD) has been reported to elapse before achieving adult pubertal status, whereas in girls, this period is 2.4 ± 1.1 years (mean ± SD). Thus, a delay of more than 4 years (some authors say 3 to 5 years) to achieve full puberty in boys and menarche in girls after the onset of the first signs of puberty warrants comprehensive evaluation.[5][6] When signs of puberty are observed before 8 years in girls and before 9 years in boys, it is defined as precocious puberty. Please see StatPearls' companion resource, "Precocious Puberty," for further information.

Delayed or absent puberty can be classified in several ways: by etiology—hypothalamic-pituitary versus gonadal dysfunction; by underlying cause, such as chronic systemic illness or inadequate nutrition (functional); and by expected course, distinguishing temporary conditions (functional causes and constitutional delay of growth and puberty) from permanent ones (hypergonadotropic hypogonadism and permanent hypogonadotropic hypogonadism). Pubertal delay and pubertal failure can be further categorized as follows: Constitutional Delay of Growth and Puberty Constitutional delay of growth and puberty (CDGP) is a subset of otherwise healthy children with a clinical history of delayed linear growth and pubertal development. Functional Hypogonadotropic Hypogonadism Functional hypogonadotropic hypogonadism is characterized by reversible suppression of the hypothalamic-pituitary-gonadal axis secondary to chronic systemic conditions, including: Chronic illnesses Malignancies and their treatments Malnutrition and eating disorders Endocrinopathies Hypogonadotropic Hypogonadism (Central Hypogonadism) Disorders characterized by deficient gonadotropin secretion due to hypothalamic or pituitary dysfunction. Congenital forms Isolated GnRH deficiency Anosmic (Kallmann syndrome): ANOS1/KAL1, FGFR1, PROK2, PROKR2, FGF8, HS6ST1, and CHD7 Non-anosmic (isolated): FGFR1, GNRH1, GNRHR, TAC3, TACR3, GPR54, FGF8, PROK2, PROKR2, HS6ST1, and NSMF/NELF Disorders of hypothalamic-pituitary-gonadal axis development, with or without other pituitary hormone deficiencies: NR0B1/DAX1, NR5A1/SF-1, HESX1, LHX3, and PROP1 Obesity-associated hypogonadotropic hypogonadism: LEP, LEPR, and PCSK1 Syndromic causes: Prader-Willi syndrome, Bardet-Biedl syndrome, CHARGE syndrome, and midline defects, such as septo-optic dysplasia Idiopathic forms Isolated gonadotropin deficiency Multiple pituitary hormone deficiency Acquired causes Tumors and cysts: Craniopharyngioma, astrocytoma, germinoma, and meningioma Infiltrative diseases: Hemochromatosis, granulomatous disease, and histiocytosis Structural or vascular injury to the hypothalamic-pituitary axis, including surgery, radiation, trauma, or pituitary apoplexy (sudden hemorrhage/infarction of the pituitary gland, which can lead to delayed or arrested pubertal development) Hypergonadotropic Hypogonadism (Primary Gonadal Failure) Conditions characterized by primary gonadal dysfunction with elevated gonadotropins

Structural or vascular injury to the hypothalamic-pituitary axis, including surgery, radiation, trauma, or pituitary apoplexy (sudden hemorrhage/infarction of the pituitary gland, which can lead to delayed or arrested pubertal development) Hypergonadotropic Hypogonadism (Primary Gonadal Failure) Conditions characterized by primary gonadal dysfunction with elevated gonadotropins Chromosomal abnormalities Turner syndrome (45, XO) Klinefelter syndrome (47, XXY) Disorders of sex steroid biosynthesis or action (primarily in males) 17α-hydroxylase deficiency (CYP17A1) 17,20-lyase deficiency (CYP17A1) 5α-reductase deficiency (SRD5A2) 17β-hydroxysteroid dehydrogenase deficiency (HSD17B3) Congenital lipoid adrenal hyperplasia (StAR) Androgen insensitivity syndrome Sertoli cell–only syndrome (Del Castillo syndrome), characterized by the absence of germ cells in the seminiferous tubules Testicular regression syndrome Acquired gonadal injury: Radiation therapy, chemotherapy, or head trauma/neurosurgery affecting the hypothalamic-pituitary region Other causes: Autoimmune polyglandular syndromes and post-infectious etiologies (eg, mumps)[1][7]

Delayed puberty affects approximately 2% of adolescents worldwide and is defined as pubertal onset occurring more than 2 SD later than the population mean. Clinically, it is characterized by the absence of testicular enlargement (testicular volume <4 mL) by age 14 in boys or the absence of breast development by age 13 in girls. CDGP is the most common cause and accounts for the majority of delayed puberty presentations, with a higher prevalence in boys than in girls. Prevalence estimates are similar across countries and populations.[8] Prevalence by Etiology In a 2002 retrospective study of 232 subjects at an academic center in the United States, the prevalence of delayed puberty was categorized by etiology.[9] The most common cause of delayed puberty was CDGP, affecting 53% of adolescents aged 18 or younger. CDGP was more common in males (63%) than in females (30%). Functional hypogonadotropic hypogonadism occurred in 19% of patients. Permanent hypogonadotropic hypogonadism comprised 12% of patients. Primary gonadal failure occurred in 13% of patients. Patients without a clearly defined condition accounted for only 3% of subjects. A 2021 study of a large retrospective cohort of children with delayed puberty found that among 392 eligible girls, the most common causes were constitutional delay (124 girls, 32%), functional hypogonadotropic hypogonadism (113 girls, 29%), and hypergonadotropic hypogonadism (primary gonadal insufficiency; 71 girls, 18%). Idiopathic hypogonadotropic hypogonadism and Kallmann syndrome (idiopathic hypogonadotropic hypogonadism in combination with anosmia) were rare, identified as part of the broader syndrome in 16 girls (4%) and as an isolated condition in 5 girls (1.3%). Other causes included hypothyroidism and hyperprolactinemia (32 girls, 8%), as well as acquired and congenital conditions involving the hypothalamus and pituitary gland (7 girls, 1.8%, and 6 girls, 1.5%, respectively).

A 2021 study of a large retrospective cohort of children with delayed puberty found that among 392 eligible girls, the most common causes were constitutional delay (124 girls, 32%), functional hypogonadotropic hypogonadism (113 girls, 29%), and hypergonadotropic hypogonadism (primary gonadal insufficiency; 71 girls, 18%). Idiopathic hypogonadotropic hypogonadism and Kallmann syndrome (idiopathic hypogonadotropic hypogonadism in combination with anosmia) were rare, identified as part of the broader syndrome in 16 girls (4%) and as an isolated condition in 5 girls (1.3%). Other causes included hypothyroidism and hyperprolactinemia (32 girls, 8%), as well as acquired and congenital conditions involving the hypothalamus and pituitary gland (7 girls, 1.8%, and 6 girls, 1.5%, respectively). Among 683 eligible boys, CDGP was the most prevalent (476 boys, 70%), followed by functional hypogonadotropic hypogonadism (110 boys, 16%). Primary gonadal failure was found in 13 boys (2%), idiopathic hypogonadotropic hypogonadism/Kallmann syndrome with a broader syndrome in 8 boys (1.2%), isolated idiopathic hypogonadotropic hypogonadism/Kallmann syndrome in 14 boys (2.0%), other endocrine conditions secondarily affecting puberty in 33 boys (4.8%), and acquired and congenital conditions involving hypothalamic/pituitary function in 11 boys (1.6%) and 2 boys (0.3%), respectively.[10] A 2022 analysis noted that Klinefelter syndrome is the most common cause of primary hypogonadism, with an incidence rate of 10 to 25:10,000 males, whereas the prevalence of Kallmann Syndrome is likely 1:4000 to 30,000. Traumatic testicular injury and infectious orchitis are relatively rare causes of primary hypogonadism (<1:10,000). The estimated prevalence of pituitary macroadenoma leading to hypogonadism is approximately 1 to 1.5:10,000 men.[11]

Delayed Puberty in Males Overall, CDGP is the most common cause of delayed puberty. Typically, affected children present with a height between −2 and −3 SDs from the mean. These children are born with normal length but experience a deceleration in growth (catch-down growth) during the first 2 to 3 years of life, falling below 2 SDs. After this initial deceleration, they continue to grow at a normal rate, but their height remains below the 3rd percentile. As their male peers experience puberty and a growth spurt, the patient continues to have a low growth velocity (2-4 cm/year) and pubertal delay. In normal boys, the growth spurt occurs at a testicular volume of 10 to 12 mL, between Tanner stages 3 and 4. In boys with CDGP and delayed puberty, the growth spurt occurs later, generally between ages 15 and 17.[12] When puberty eventually occurs, catch-up growth continues until the patient reaches his predicted target height, which may not occur until after age 17 or 18. The patient's bone age correlates with his current height and may be delayed by 2 or more years compared to his chronological age.[4] History often reveals a sibling or parent who was a late bloomer. For example, the father may not have experienced a growth spurt until age 15 or 16. CDGP is typically a diagnosis of exclusion. However, it is often challenging to differentiate between CDGP and hypogonadotropic hypogonadism. Despite a strong familial component, the causative genetic basis for this condition remains to be elucidated. CDGP is likely polygenic in origin, reflecting the cumulative effect of variants of small effect.[12]

Overall, CDGP is the most common cause of delayed puberty. Typically, affected children present with a height between −2 and −3 SDs from the mean. These children are born with normal length but experience a deceleration in growth (catch-down growth) during the first 2 to 3 years of life, falling below 2 SDs. After this initial deceleration, they continue to grow at a normal rate, but their height remains below the 3rd percentile. As their male peers experience puberty and a growth spurt, the patient continues to have a low growth velocity (2-4 cm/year) and pubertal delay. In normal boys, the growth spurt occurs at a testicular volume of 10 to 12 mL, between Tanner stages 3 and 4. In boys with CDGP and delayed puberty, the growth spurt occurs later, generally between ages 15 and 17.[12] When puberty eventually occurs, catch-up growth continues until the patient reaches his predicted target height, which may not occur until after age 17 or 18. The patient's bone age correlates with his current height and may be delayed by 2 or more years compared to his chronological age.[4] History often reveals a sibling or parent who was a late bloomer. For example, the father may not have experienced a growth spurt until age 15 or 16. CDGP is typically a diagnosis of exclusion. However, it is often challenging to differentiate between CDGP and hypogonadotropic hypogonadism. Despite a strong familial component, the causative genetic basis for this condition remains to be elucidated. CDGP is likely polygenic in origin, reflecting the cumulative effect of variants of small effect.[12] Hypogonadotropic hypogonadism occurs when maturation of the hypothalamic-pituitary-gonadal axis is delayed or interrupted. There is a partial or complete deficiency of GnRH, leading to reduced secretion of LH and FSH, ultimately resulting in decreased testosterone production.[13] Hypogonadotropic hypogonadism may be congenital, acquired, or functional, secondary to chronic systemic illness or nutrient deficiency. If the patient has anosmia (the absence of smell), Kallmann syndrome warrants strong diagnostic consideration. Kallmann syndrome results from mutations in the KAL1 or FGFR1 (fibroblast growth factor receptor 1) genes.[14] The development of the olfactory system is closely linked to the migration of GnRH neurons during early embryogenesis. Other associated physical findings may include a cleft lip or palate, a single central incisor, hypodontia, eye defects, or hearing impairments. A brain magnetic resonance imaging (MRI) may help support the diagnosis and rule out a tumor or lesion along the hypothalamic-pituitary-gonadal axis. Brain tumors such as adenomas and craniopharyngiomas are relatively uncommon causes of hypogonadotropic hypogonadism in children. Suspicion for a cranial mass is advisable when a child presents with headaches, dizziness, vomiting, and vision changes.

Hypogonadotropic hypogonadism occurs when maturation of the hypothalamic-pituitary-gonadal axis is delayed or interrupted. There is a partial or complete deficiency of GnRH, leading to reduced secretion of LH and FSH, ultimately resulting in decreased testosterone production.[13] Hypogonadotropic hypogonadism may be congenital, acquired, or functional, secondary to chronic systemic illness or nutrient deficiency. If the patient has anosmia (the absence of smell), Kallmann syndrome warrants strong diagnostic consideration. Kallmann syndrome results from mutations in the KAL1 or FGFR1 (fibroblast growth factor receptor 1) genes.[14] The development of the olfactory system is closely linked to the migration of GnRH neurons during early embryogenesis. Other associated physical findings may include a cleft lip or palate, a single central incisor, hypodontia, eye defects, or hearing impairments. A brain magnetic resonance imaging (MRI) may help support the diagnosis and rule out a tumor or lesion along the hypothalamic-pituitary-gonadal axis. Brain tumors such as adenomas and craniopharyngiomas are relatively uncommon causes of hypogonadotropic hypogonadism in children. Suspicion for a cranial mass is advisable when a child presents with headaches, dizziness, vomiting, and vision changes. A transient form of hypogonadotropic hypogonadism is the second most common cause of delayed puberty after CDGP. Known as functional hypogonadotropic hypogonadism, it results from inadequate caloric intake, either due to increased caloric expenditure or to the dissipation of anabolic energy in certain chronic conditions; puberty is a state of high energy demand. Almost all chronic systemic illnesses may cause functional hypogonadotropic hypogonadism if left untreated. This condition is typically reversible with treatment of the underlying condition.

A transient form of hypogonadotropic hypogonadism is the second most common cause of delayed puberty after CDGP. Known as functional hypogonadotropic hypogonadism, it results from inadequate caloric intake, either due to increased caloric expenditure or to the dissipation of anabolic energy in certain chronic conditions; puberty is a state of high energy demand. Almost all chronic systemic illnesses may cause functional hypogonadotropic hypogonadism if left untreated. This condition is typically reversible with treatment of the underlying condition. Hypergonadotropic hypogonadism conditions are characterized by primary gonadal dysfunction and elevated gonadotropins. Low testosterone levels lead to increased secretion of GnRH, LH, and FSH. The etiology of hypergonadotropic hypogonadism can be either acquired or congenital. Acquired causes include radiation exposure to the testes to treat malignancy, gonadotoxic chemotherapy, surgery for cryptorchism or torsion, or infection, such as mumps orchitis.[4] In males, Klinefelter syndrome is the most common congenital cause of primary gonadal insufficiency. Klinefelter syndrome results from aneuploidy of the sex chromosomes, most commonly a 47, XXY karyotype. Affected individuals typically present with tall stature, disproportionately long limbs, eunuchoid body habitus, gynecomastia, and neurological or behavioral problems. However, the hallmark sign is small testes (less than 4 mL) that are firm; this typically leads to infertility due to oligospermia or azoospermia.[15] Lastly, patients with hypergonadotropic hypogonadism may have vanishing testis syndrome, also known as testicular regression syndrome. Testicular regression syndrome occurs in approximately 5% of cases of cryptorchidism. Although the cause of testicular regression syndrome remains unclear, the hypothesis is that vascular thrombosis or torsion occurring in the antenatal or perinatal period causes testicular degeneration. Therefore, a fetus that initially develops normal testes in utero is born with non-palpable testes and a rudimentary spermatic cord.[16] Delayed Puberty in Females

Hypergonadotropic hypogonadism conditions are characterized by primary gonadal dysfunction and elevated gonadotropins. Low testosterone levels lead to increased secretion of GnRH, LH, and FSH. The etiology of hypergonadotropic hypogonadism can be either acquired or congenital. Acquired causes include radiation exposure to the testes to treat malignancy, gonadotoxic chemotherapy, surgery for cryptorchism or torsion, or infection, such as mumps orchitis.[4] In males, Klinefelter syndrome is the most common congenital cause of primary gonadal insufficiency. Klinefelter syndrome results from aneuploidy of the sex chromosomes, most commonly a 47, XXY karyotype. Affected individuals typically present with tall stature, disproportionately long limbs, eunuchoid body habitus, gynecomastia, and neurological or behavioral problems. However, the hallmark sign is small testes (less than 4 mL) that are firm; this typically leads to infertility due to oligospermia or azoospermia.[15] Lastly, patients with hypergonadotropic hypogonadism may have vanishing testis syndrome, also known as testicular regression syndrome. Testicular regression syndrome occurs in approximately 5% of cases of cryptorchidism. Although the cause of testicular regression syndrome remains unclear, the hypothesis is that vascular thrombosis or torsion occurring in the antenatal or perinatal period causes testicular degeneration. Therefore, a fetus that initially develops normal testes in utero is born with non-palpable testes and a rudimentary spermatic cord.[16] Delayed Puberty in Females CDGP is less common in girls. When it does occur, family history typically includes a sibling or parent who was a late bloomer. Functional hypogonadotropic hypogonadism is a common cause of delayed puberty in females. This condition typically develops secondary to conditions that reduce total body fat, which is commonly associated with anorexia nervosa or excessive exercise in females. Both involve a significant reduction in caloric intake, which also lowers leptin levels, leading to gonadotropin deficiency. Decreased LH and FSH secretion, combined with lower body fat, leads to failure of hypothalamic-pituitary-gonadal axis activation and thus delays puberty.

CDGP is less common in girls. When it does occur, family history typically includes a sibling or parent who was a late bloomer. Functional hypogonadotropic hypogonadism is a common cause of delayed puberty in females. This condition typically develops secondary to conditions that reduce total body fat, which is commonly associated with anorexia nervosa or excessive exercise in females. Both involve a significant reduction in caloric intake, which also lowers leptin levels, leading to gonadotropin deficiency. Decreased LH and FSH secretion, combined with lower body fat, leads to failure of hypothalamic-pituitary-gonadal axis activation and thus delays puberty. Kallmann syndrome can cause delayed puberty in females; however, it is relatively uncommon and occurs more frequently in males. This male predominance is mainly attributable to X-linked recessive inheritance, although autosomal dominant and autosomal recessive inheritance patterns have also been described.[13] In females, hypergonadotropic hypogonadism results from primary ovarian failure and is either acquired or congenital. Acquired causes include receiving radiation therapy or gonadotoxic chemotherapy for the treatment of cancers and malignancies. Autoimmune destruction of the ovaries can also lead to hypergonadotropic hypogonadism. However, this is typically associated with other autoimmune disorders in patients who have more than 1 autoimmune diagnosis, such as type 1 diabetes or Hashimoto thyroiditis (eg, autoimmune polyglandular type I or type II syndromes).[4] When hypergonadotropic hypogonadism is associated with short stature, Turner syndrome must be considered. Turner syndrome results from a partial or complete absence of an X chromosome. Patients may present in infancy with nuchal translucency, cystic hygroma, or lymphedema. Common clinical features include a webbed neck, a broad chest with widely spaced nipples, and short stature. Other common associations with Turner syndrome include a bicuspid aortic valve; coarctation of the aorta; autoimmune disorders, such as celiac disease; and congenital kidney malformations, such as horseshoe kidneys. Therefore, the management of Turner syndrome may require an interprofessional team of different specialists.[17][18] Please see StatPearls' companion resource, "Turner Syndrome," for further information.

In females, hypergonadotropic hypogonadism results from primary ovarian failure and is either acquired or congenital. Acquired causes include receiving radiation therapy or gonadotoxic chemotherapy for the treatment of cancers and malignancies. Autoimmune destruction of the ovaries can also lead to hypergonadotropic hypogonadism. However, this is typically associated with other autoimmune disorders in patients who have more than 1 autoimmune diagnosis, such as type 1 diabetes or Hashimoto thyroiditis (eg, autoimmune polyglandular type I or type II syndromes).[4] When hypergonadotropic hypogonadism is associated with short stature, Turner syndrome must be considered. Turner syndrome results from a partial or complete absence of an X chromosome. Patients may present in infancy with nuchal translucency, cystic hygroma, or lymphedema. Common clinical features include a webbed neck, a broad chest with widely spaced nipples, and short stature. Other common associations with Turner syndrome include a bicuspid aortic valve; coarctation of the aorta; autoimmune disorders, such as celiac disease; and congenital kidney malformations, such as horseshoe kidneys. Therefore, the management of Turner syndrome may require an interprofessional team of different specialists.[17][18] Please see StatPearls' companion resource, "Turner Syndrome," for further information. Another condition that may present as primary amenorrhea in females is Mayer-Rokitansky-Küster-Hauser syndrome, caused by developmental defects of the uterus and upper vagina without any significant hormonal problems. This syndrome occurs in 1 out of 4500 to 5000 female newborns. Affected individuals have normal ovarian development with normal gonadotropin and estrogen levels, leading to normal secondary sexual characteristics; however, they do not have menarche. These individuals may have other extragenital malformations, commonly of the spine and kidneys, and, less commonly, of the ear, heart, and nervous system. The presence of these associated anomalies defines Mayer-Rokitansky-Küster-Hauser type II. Specific patterns include MURCS syndrome (Müllerian agenesis, Renal malformations, and Cervicothoracic Somite dysplasia). No specific etiology has been identified; however, several likely gene-disrupting variants in the PAX8, BMP4, BMP7, TBX6, HOXA10, EMX2, and WNT9B regions have been proposed as linked to this condition in a recent large multicenter study.[19][20][21]

Pertinent History Birth history: Breech presentation, prolonged jaundice, hypoglycemia, and micropenis (in males) may suggest multiple pituitary hormone deficiency associated with hypogonadotropic hypogonadism. Developmental history: Clinicians should assess whether the patient has missed any developmental milestones or has been diagnosed with any developmental delay that may suggest a genetic syndrome. History of present illness: The clinician should inquire about any signs of puberty that the child or the caregivers have noticed, such as breast development, testicular enlargement, body odor, axillary hair, pubertal hair, or acne. The distinction between adrenarche and puberty should be made. A thorough review of systems can help to identify or exclude systemic causes of pubertal delay, as functional hypogonadotropic hypogonadism is the second most common cause of delayed or failed puberty after physiological delay. A young child complaining of headaches and blurry vision/field cuts in vision should undergo evaluation for a brain mass. A history of galactorrhoea may indicate hyperprolactinemia as the cause of delayed puberty. Dietary history and physical activity: Low-calorie intake and high levels of physical activity may be associated with delayed or stalled puberty. Family history: Were any biological siblings or parents considered late bloomers in their family? CDGP versus isolated hypogonadotropic hypogonadism. Medications/treatments: If the patient has a history of malignancy, clinicians should ask about gonadotoxic chemotherapy (commonly alkylating agents) and radiation to the hypothalamic-pituitary area, gonads, or whole body. A history of brain trauma (hypothalamo-pituitary area) or gonads is also relevant. Surgical history: Did the patient undergo a surgical correction of cryptorchidism or brain surgery (hypothalamo-pituitary area), which may result in primary or secondary gonadal failure, respectively? Essential Components of the Physical Examination Tanner staging: This staging should always be documented to assess the current status and progression of puberty (see Tables Tanner Staging for Females and Tanner Staging for Males). In some cases, a normal Tanner stage may obviate the need for extensive testing and provide reassurance to patients and families. Table Table 1. Tanner Staging for Females. Table Table 2. Tanner Staging for Males.

Tanner staging: This staging should always be documented to assess the current status and progression of puberty (see Tables Tanner Staging for Females and Tanner Staging for Males). In some cases, a normal Tanner stage may obviate the need for extensive testing and provide reassurance to patients and families. Table Table 1. Tanner Staging for Females. Table Table 2. Tanner Staging for Males. Anthropometric assessment: Measurements should include height, weight, and body mass index, using current age- and sex-appropriate growth curves to assess associated growth axis defects or systemic illnesses. Segmental length and arm span may provide clues to hypogonadism (arm span >5 cm greater than height; upper-to-lower segment ratio <0.85-0.80). Decreased linear growth with preserved weight gain may indicate pituitary hormone deficiency. Comprehensive physical examination: A thorough examination should include evidence of organ-system involvement and dysmorphic features, which may corroborate or refute the history findings discussed above. Midline defects or a single upper incisor may indicate pituitary involvement. CHARGE (Coloboma, Heart defects, Atresia choana, Growth retardation, Genital abnormalities, Ear abnormalities) syndrome is associated with hypogonadotropic hypogonadism. Turner, Noonan, Bardet-Biedl, and Prader-Willi syndromes are associated with delayed puberty, short stature, and other dysmorphic features.

Evaluation of delayed puberty builds on the history and physical examination to confirm the diagnosis, define the underlying etiology, and guide appropriate laboratory testing and imaging. Measurements of morning LH, FSH, testosterone/estradiol, preferably using ultra-sensitive assays, provide clues about the current state of pubertal development and etiology (central versus gonadal), which may help determine the diagnosis. Clinical findings should guide additional laboratory tests and typically include a complete blood count, comprehensive metabolic panel, free T4 and thyroid-stimulating hormone, anti-tissue transglutaminase for relevant systemic illnesses, and erythrocyte sedimentation rate and/or C-reactive protein for chronic inflammatory conditions. Serum prolactin is also part of the evaluation, especially if history and examination are suggestive or the initial evaluation suggests hypogonadotropic hypogonadism. If panhypopituitarism or growth hormone deficiency is a concern, insulin-like growth factor 1 and/or growth hormone stimulation testing is required.[22][23] A pediatric endocrinologist may perform a GnRH stimulation test, often to differentiate isolated hypogonadotropic hypogonadism from CDGP or when LH/FSH are inconclusive. There is no single diagnostic test to distinguish between these entities; therefore, longitudinal follow-up is often required and typically clarifies the diagnosis. A recent study suggested that FSH-stimulated inhibin B, with cutoffs of 116.14 pg/mL in males and 116.50 pg/mL in females, had 100% sensitivity and specificity for entry into puberty.[23][4][23] Another study showed that all participants with kisspeptin-stimulated LH of 0.8 mIU/mL or more subsequently progressed through puberty (n = 8). In contrast, participants exhibiting LH responses to kisspeptin ≤ 0.4 mIU/mL did not reach puberty until age 18 (n = 8). In this study, kisspeptin stimulation outperformed GnRH-stimulated LH, inhibin B, and genetic testing in predicting pubertal outcomes.[24] Genetic testing: When there is suspicion of a syndrome or a genetic cause, karyotype/array/next-generation sequencing-based testing should be considered, as appropriate.[4]

A pediatric endocrinologist may perform a GnRH stimulation test, often to differentiate isolated hypogonadotropic hypogonadism from CDGP or when LH/FSH are inconclusive. There is no single diagnostic test to distinguish between these entities; therefore, longitudinal follow-up is often required and typically clarifies the diagnosis. A recent study suggested that FSH-stimulated inhibin B, with cutoffs of 116.14 pg/mL in males and 116.50 pg/mL in females, had 100% sensitivity and specificity for entry into puberty.[23][4][23] Another study showed that all participants with kisspeptin-stimulated LH of 0.8 mIU/mL or more subsequently progressed through puberty (n = 8). In contrast, participants exhibiting LH responses to kisspeptin ≤ 0.4 mIU/mL did not reach puberty until age 18 (n = 8). In this study, kisspeptin stimulation outperformed GnRH-stimulated LH, inhibin B, and genetic testing in predicting pubertal outcomes.[24] Genetic testing: When there is suspicion of a syndrome or a genetic cause, karyotype/array/next-generation sequencing-based testing should be considered, as appropriate.[4] Imaging: A bone age assessment (x-ray of the non-dominant wrist and hand) may help predict adult height and assist in determining the condition's chronology. An ultrasound of the testicles can help evaluate cryptorchidism or a palpable mass. When there is suspicion of a brain mass, such as a craniopharyngioma, the clinician should obtain a brain MRI.[22] Brain MRI with olfactory cuts also helps diagnose Kallmann syndrome, in which the absence of the olfactory sulcus and aplasia or hypoplasia of the olfactory bulb are suggestive of this diagnosis.

CDGP Following a diagnosis of CDGP, treatment is typically guided by the patient's and parental goals. Close observation and reassurance are appropriate, especially if there is no significant psychosocial distress. A short course of treatment with low doses of testosterone for males or estrogen for females is often initiated when puberty and growth cause substantial psychosocial stress and low self-esteem for a child. Indicators such as a history of bullying, declining academic performance, or withdrawal from athletic activities may support the decision to initiate treatment. Treatment can improve growth velocity, sexual maturation, and mental well-being without producing adverse effects or significantly affecting the final target height.[1] In boys with CDGP, testosterone therapy may be administered orally, transdermally, or intramuscularly (IM); however, the IM route is most commonly used due to extensive clinical experience and predictable efficacy and safety. Testosterone enanthate injection (or cypionate/propionate) at a dosage of 50 to 100 mg IM monthly for 3 to 6 months is sufficient to initiate pubertal development. Subcutaneous injections may also be considered for ease of administration by family members at home, although experience with this route is limited. In girls with CDGP, 17β-estradiol administered orally or via a transdermal patch is the preferred therapy. Treatment is typically initiated at one-fourth to one-eighth of the adult replacement dose. A commonly used regimen involves a 25-µg estradiol transdermal patch divided into 4 pieces and applied twice weekly for 4 to 6 months. Once treatment has begun, patients should be monitored regularly for signs of pubertal development, including testicular enlargement in males and breast development in females. If they do not show any signs of puberty by the end of treatment, further management is individualized, with discussion with the family about whether to repeat the course or to wait.[4][17] For patients who are more concerned about short stature than about delayed puberty, growth hormone therapy has been used to increase height. However, it has not been shown to significantly affect final adult height in adolescents with CDGP and is therefore not recommended for this indication by pediatric endocrine societies.[1] Hypogonadotropic Hypogonadism

Once treatment has begun, patients should be monitored regularly for signs of pubertal development, including testicular enlargement in males and breast development in females. If they do not show any signs of puberty by the end of treatment, further management is individualized, with discussion with the family about whether to repeat the course or to wait.[4][17] For patients who are more concerned about short stature than about delayed puberty, growth hormone therapy has been used to increase height. However, it has not been shown to significantly affect final adult height in adolescents with CDGP and is therefore not recommended for this indication by pediatric endocrine societies.[1] Hypogonadotropic Hypogonadism The most common causes of hypogonadotropic hypogonadism are temporary, namely, CDGP and functional hypogonadotropic hypogonadism. In cases secondary to an underlying systemic illness, treatment of the primary condition often results in spontaneous resumption of pubertal development. Sometimes these children need external hormone support when the underlying illness is difficult to treat and the child is significantly lagging behind peers in pubertal development. Hormonal support in this situation helps alleviate the child's psychosocial distress and limits the deficit in bone mass relative to age- and gender-appropriate peak bone mass. Permanent Hypogonadism Patients diagnosed with permanent hypogonadism, either from primary gonadal failure or secondary to a permanently non-functioning hypothalamic-pituitary-gonadal axis (organic cause/idiopathic), require lifelong hormone supplementation. In males with primary gonadal failure, IM testosterone is the treatment of choice. A low dose of testosterone is started and gradually increased over time until adult levels are achieved. An example is starting replacement with testosterone enanthate or cypionate at 50 mg monthly, which can be increased every 4 to 6 months. The final adult dose varies individually, but approximately 200 mg fortnightly is sufficient for most males. This dose can be reached in approximately 3 years after starting testosterone. Once the patient is on adult replacement doses, a 12-weekly depot injection of testosterone undecanoate can be used. Therapy can be monitored by serum testosterone levels, which should be targeted to the mid-range for age and pubertal stage.

Patients diagnosed with permanent hypogonadism, either from primary gonadal failure or secondary to a permanently non-functioning hypothalamic-pituitary-gonadal axis (organic cause/idiopathic), require lifelong hormone supplementation. In males with primary gonadal failure, IM testosterone is the treatment of choice. A low dose of testosterone is started and gradually increased over time until adult levels are achieved. An example is starting replacement with testosterone enanthate or cypionate at 50 mg monthly, which can be increased every 4 to 6 months. The final adult dose varies individually, but approximately 200 mg fortnightly is sufficient for most males. This dose can be reached in approximately 3 years after starting testosterone. Once the patient is on adult replacement doses, a 12-weekly depot injection of testosterone undecanoate can be used. Therapy can be monitored by serum testosterone levels, which should be targeted to the mid-range for age and pubertal stage. In females, a low-dose 17-beta estradiol preparation (oral or transdermal patch) is the preferred initial treatment. Estrogen is also used incrementally over time until breakthrough vaginal bleeding occurs or 12 to 24 months of treatment have passed. The recommendation is then for patients to start combination estrogen and progesterone therapy to maintain normal monthly withdrawal bleeding. The transition helps the body experience more normal physiological menstrual cycles.[4] Commonly used hormone replacement therapies include oral estrogen plus progesterone or transdermal estrogen patches with oral progesterone; both combinations are more physiological than oral contraceptive pills. Pubertal induction in females may follow established protocols used for patients with Turner syndrome. Please see StatPearls' companion resource, "Turner Syndrome," for further information.

In females, a low-dose 17-beta estradiol preparation (oral or transdermal patch) is the preferred initial treatment. Estrogen is also used incrementally over time until breakthrough vaginal bleeding occurs or 12 to 24 months of treatment have passed. The recommendation is then for patients to start combination estrogen and progesterone therapy to maintain normal monthly withdrawal bleeding. The transition helps the body experience more normal physiological menstrual cycles.[4] Commonly used hormone replacement therapies include oral estrogen plus progesterone or transdermal estrogen patches with oral progesterone; both combinations are more physiological than oral contraceptive pills. Pubertal induction in females may follow established protocols used for patients with Turner syndrome. Please see StatPearls' companion resource, "Turner Syndrome," for further information. There is increasing evidence supporting the use of human chorionic gonadotropin and recombinant FSH in various combinations. Typically, human chorionic gonadotropin doses range from 500 to 3000 IU twice weekly. Doses can be adjusted based on serum testosterone levels. Recombinant FSH is used at doses of 75 to 225 IU 2 to 3 times weekly to achieve fertility in males with hypogonadotropic hypogonadism.[25][26] When families choose this treatment, clinicians must provide careful counseling to set realistic expectations, avoid disappointment in unsuccessful cases, and discuss the advantages (eg, possible fertility) and disadvantages (eg, more frequent injections and higher costs).

The differential diagnosis of delayed puberty focuses on identifying the underlying etiology, as outlined in the preceding section, and distinguishing between constitutional, functional, hypogonadotropic, and hypergonadotropic causes. Delayed Puberty in Males and Females Chronic illnesses: Anemia, inflammatory bowel disease, cystic fibrosis, untreated congenital heart disease, celiac disease, malabsorption syndromes, chronic liver or kidney disease, tubular dysfunctions, nutritional deprivation, and chronic infections. Psychological factors: Depression and anxiety Endocrinopathies: Hypothyroidism, Cushing syndrome, and other endocrine disorders Delayed Puberty in Males Constitutional delay of puberty and growth Hypogonadotropic hypogonadism Acquired Chronic illness: Cystic fibrosis, sickle cell anemia, and celiac disease Psychosocial factors: Anxiety and depression Genetic Kallmann syndrome and Prader-Willi syndrome Brain mass or tumor Hypergonadotropic hypogonadism Acquired Infection/trauma Radiation therapy Testicular surgery Genetic Klinefelter syndrome Testicular regression syndrome Delayed Puberty in Females Constitutional delay in puberty and growth Hypogonadotropic hypogonadism Acquired Chronic illness: Cystic fibrosis, sickle cell anemia, and celiac disease Psychosocial factors: Anorexia nervosa, excessive exercise, depression, and anxiety Genetic Kallmann syndrome Brain mass or tumor Hypergonadotropic hypogonadism Acquired Radiation therapy Surgery on the ovaries Genetic Autoimmune ovarian failure Turner syndrome

The prognosis of delayed puberty depends on the underlying condition. CDGP generally has an excellent prognosis with either expectant therapy or treatment. One extensive analysis showed the probability that a child with idiopathic delayed puberty at a given age enters puberty within a specific time interval. In girls, the likelihood of entering puberty in the next year was 40 ± 5% (estimate ± SE) for a 12-year-old, 62 ± 13% for a 13-year-old, and 74 ± 36% for a 15.5-year-old girl. In boys, the probability of entering puberty in the next year increased from about 40% at 13.5 years to 68% (±22%) at 16 years, but fell to 48% (±32%) if a boy had not entered puberty by 16.5 years. The same analysis also predicted the probability of not having entered puberty by 18 years. If a child has not entered puberty by a certain age, the likelihood of not entering puberty increases progressively from 3 ± 2% at 12 years to 49 ± 32% by 15 years. Similarly, in boys, the probability rose from 4 ± 1% at 13.5 years to 84 ± 36% by 17 years. These findings suggest that it is prudent to wait for spontaneous puberty onset in likely CDGP children until approximately 15 to 15.5 years in girls and approximately 16 years in boys, after which the chances of spontaneously entering puberty become progressively lower.[10] Although patients with hypergonadotropic hypogonadism develop normal appearing secondary sexual characteristics in both genders with appropriate hormone replacement, fertility prospects remain minimal for this group. Patients with hypogonadotropic hypogonadism have satisfactory fertility outcomes with combined gonadotropin treatment.[25][26]

Delayed puberty can have substantial psychosocial and emotional consequences during adolescence, a developmental period in which physical maturation strongly influences self-image and peer relationships. Affected adolescents may experience social withdrawal, bullying, low self-esteem, anxiety, depressive symptoms, and academic stress related to feeling different from peers. In CDGP, it is important to reassure patients and families that this is a normal variation in pubertal timing and that treatment may not significantly alter predicted adult height, which can help mitigate anxiety and distress.[12] In contrast, hypogonadism is associated with potential medical complications beyond psychosocial effects, including adverse musculoskeletal outcomes such as reduced bone mineral density and altered body composition. The full spectrum of complications varies by etiology and may reflect underlying genetic syndromes, chronic systemic disease, or sequelae of prior medical therapies. When clinicians initiate treatment for delayed puberty, potential therapy-related adverse effects may occur. For example, testosterone therapy may be associated with erythrocytosis, weight gain, prostate hypertrophy, premature epiphyseal closure at high doses, and priapism, particularly in patients with sickle cell disease. Intramuscular administration may also cause local injection-site reactions, including pain, erythema, and inflammation.

Most adolescents with delayed puberty initially present to their primary care clinician or practitioner. The initial evaluation includes a detailed history, a thorough physical examination, growth assessment, and basic laboratory testing. Referral to an endocrinologist or pediatric endocrinologist is appropriate when pubertal delay is marked, pubertal development does not progress with observation, growth velocity is abnormal, laboratory findings suggest hypogonadism or another endocrine disorder, or there is concern for an underlying systemic or genetic condition. The pediatric endocrinologist or endocrinologist serves as the primary specialist, coordinating the evaluation and long-term management of delayed puberty and consulting other disciplines as needed. A medical geneticist and genetic counselor may become involved when a genetic or specific syndrome is suspected. Neurosurgical consultation is warranted when an intracranial space-occupying lesion is identified as the cause of hypogonadism. Psychologists and licensed clinical social workers can help address psychosocial distress related to delayed pubertal development. Pharmacists assist with the safe selection, dosing, and delivery of hormone therapies and other treatments, whereas radiologists play a key role in neuroimaging, particularly in cases of hypogonadotropic hypogonadism.

Clinicians should counsel patients and families on the typical sequence and earliest signs of puberty in both sexes, including breast development and pubic hair growth in girls and testicular enlargement and genital growth in boys. Education should also include the expected age range for pubertal onset, approximately 8 to 13 years in girls and 9 to 14 years in boys, so that families have appropriate expectations for normal variation. Caregivers should be advised to seek medical evaluation when pubertal development appears unusually early, delayed, or arrested, as timely assessment can distinguish benign variants from pathologic causes. Primary care clinicians play a key role in recognizing the broad etiologic spectrum of delayed puberty, identifying red flags for serious underlying disease, and providing reassurance when findings are consistent with constitutional or transient causes. In selected patients, treatment options such as gonadotropin therapy may be discussed by endocrinologists to induce pubertal development and, when appropriate, preserve fertility, which can also help alleviate psychosocial distress associated with delayed puberty.

Delayed puberty has consequences that extend well beyond the delayed development of secondary sexual characteristics, affecting emotional well-being, self-esteem, social interactions, and academic performance. For this reason, optimal care requires an interprofessional approach that addresses both physical maturation and the psychosocial impact of delayed development. Delayed puberty is often first identified by a caregiver or the child's primary care clinician. When concern arises, referral to a pediatric endocrinologist is typically warranted for further evaluation and longitudinal management. Diagnostic testing, including laboratory studies and imaging, is performed in collaboration with laboratory personnel, radiologic technologists, radiologists, and, when indicated, medical geneticists to clarify the underlying etiology. Management may require additional specialty involvement depending on the cause. For example, suspected intracranial pathology requires coordination with neurosurgery and oncology teams. Patients experiencing low self-esteem, depression, or social withdrawal benefit from referral to mental health professionals for counseling and support. Social workers play an essential role in ensuring families have access to appropriate social, educational, and financial resources and in helping families navigate complex care pathways. Education of parents and caregivers regarding the condition, expected course, and prognosis is essential. Nurses play a central role in reinforcing education, monitoring pubertal progression, and maintaining communication between the family and the clinical team. Although CDGP often requires reassurance alone, many other etiologies necessitate pharmacologic intervention. In these cases, pharmacists support the safe selection, preparation, and administration of therapies such as sex steroids and gonadotropins. Ongoing monitoring of clinical response and laboratory parameters is critical, and coordination among primary care clinicians, nurses, and specialists ensures timely management adjustments when expected outcomes are not achieved.