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Delayed Puberty


Andrew Calabria

, MD, The Children's Hospital of Philadelphia

Last full review/revision Jul 2020| Content last modified Jul 2020
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Delayed puberty is absence of sexual maturation at the expected time. Diagnosis is by measurement of gonadal hormones (testosterone and estradiol), luteinizing hormone, and follicle-stimulating hormone. Treatment, when necessary, usually involves specific hormone replacement.

Delayed puberty may result from constitutional delay, which often occurs in adolescents with a family history of delayed growth. Such children are often referred to as "late bloomers." Prepubertal growth velocity is normal, but skeletal maturation and adolescent growth spurt are delayed; sexual maturation is delayed but normal.

Other causes include genetic disorders ( Turner syndrome Turner Syndrome In Turner syndrome, girls are born with one of their two X chromosomes partly or completely missing. Diagnosis is based on clinical findings and is confirmed by cytogenetic analysis. Treatment... read more Turner Syndrome in girls, Klinefelter syndrome Klinefelter Syndrome (47,XXY) Klinefelter syndrome is the presence of two or more X chromosomes plus one Y, resulting in a phenotypic male. Diagnosis is based on clinical findings and is confirmed by cytogenetic analysis... read more Klinefelter Syndrome (47,XXY) in boys), central nervous system (CNS) disorders (eg, hypothalamic or pituitary tumors that reduce gonadotropin secretion), CNS radiation, certain chronic disorders (eg, poorly controlled diabetes mellitus Diabetes Mellitus in Children and Adolescents Diabetes mellitus involves absence of insulin secretion (type 1) or peripheral insulin resistance (type 2), causing hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , inflammatory bowel disorders Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal... read more , renal disorders, cystic fibrosis Cystic Fibrosis Cystic fibrosis is an inherited disease of the exocrine glands affecting primarily the gastrointestinal and respiratory systems. It leads to chronic lung disease, exocrine pancreatic insufficiency... read more Cystic Fibrosis ), Kallman syndrome Secondary hypogonadism , undernutrition Overview of Undernutrition Undernutrition is a form of malnutrition. (Malnutrition also includes overnutrition.) Undernutrition can result from inadequate ingestion of nutrients, malabsorption, impaired metabolism, loss... read more / eating disorders Introduction to Eating Disorders Eating disorders involve a persistent disturbance of eating or of behavior related to eating that Alters consumption or absorption of food Significantly impairs physical health and/or psychosocial... read more , and excess physical activity, especially in girls ( 1 General reference Delayed puberty is absence of sexual maturation at the expected time. Diagnosis is by measurement of gonadal hormones (testosterone and estradiol), luteinizing hormone, and follicle-stimulating... read more ).

General reference

  • 1. Howard SR, Dunkel L: The genetic basis of delayed puberty. Neuroendocrinology 106(3):283–291, 2018. doi: 10.1159/000481569

Symptoms and Signs of Delayed Puberty

Adolescents may be noticeably shorter than peers, can be teased or bullied, and often need help in coping with and managing social concerns. Although adolescents are typically uncomfortable about being different from their peers, boys are more likely than girls to feel psychologic stress and embarrassment resulting from short stature and delayed puberty.

Manifestations of possible causes of delayed puberty

Signs of possible chronic disease include an abrupt change in growth, undernutrition, discordant development (eg, pubic hair without breast development), or stalled pubertal development (ie, puberty starts then fails to progress).

Diagnosis of Delayed Puberty

  • Clinical criteria

  • Measurement of testosterone or estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH)

  • Imaging studies

  • Genetic testing

The initial evaluation of delayed puberty should consist of a complete history and physical examination to evaluate pubertal development, nutritional status, and growth. Depending on findings, laboratory tests for other causes of slow growth should be considered:

  • Hypothyroidism (eg, thyroid-stimulating hormone, thyroxine)

  • Renal disorders (eg, electrolytes, creatinine levels)

  • Inflammatory and immune conditions (eg, tissue transglutaminase antibodies, C-reactive protein)

  • Hematologic disorders (eg, complete blood count with differential)

Criteria for delayed puberty

In girls, delayed puberty is diagnosed if one of the following occurs:

  • No breast development by age 13

  • > 3 years elapsed between the beginning of breast growth and menarche

  • Menstruation does not occur by age 16

In boys, delayed puberty is diagnosed if one of the following occurs:

  • No testicular enlargement by age 14

  • > 5 years elapsed between initial and complete growth of the genitals

Short stature, decreased growth velocity, or both may indicate delayed puberty in either sex. Although many children seem to be starting puberty earlier than in past years, there are no indications that the criteria for delayed puberty should change.

Hormonal testing

LH, FSH, and testosterone or estradiol levels are measured. LH and FSH are gonadotropins secreted by the pituitary, which stimulate production of sex hormones. LH and FSH levels are the most useful initial tests (see also algorithm Evaluation of primary amenorrhea Evaluation of primary amenorrhea [a] Evaluation of primary amenorrhea [a] ).

Elevated serum LH and FSH levels indicate

Low FSH and LH levels along with low testosterone and estradiol levels in children with short stature and delayed pubertal development may indicate

Current assays for testosterone and estradiol levels do not always distinguish early pubertal from prepubertal levels. Constitutional delay of puberty Secondary hypogonadism is more commonly diagnosed in boys, partly because adolescent boys are more distressed if they do not mature at the same rate as their peers and are thus more likely to present for evaluation. It can be difficult to distinguish constitutional delay of puberty from permanent causes of hypogonadotropic hypogonadism. Chronic disorders that cause inadequate nutrition can delay puberty by impairing gonadotropin-releasing hormone release. Permanent forms of hypogonadotropic hypogonadism are more likely if there is a lack of response to one or two short courses of testosterone therapy. If a pituitary disorder is suspected, levels of other pituitary hormones should be measured because hypogonadotropic hypogonadism can be isolated or associated with other hormone deficiencies.

Imaging studies

When growth is abnormal, bone age x-ray should be the first test. Bone age is determined from an x-ray of the left hand (by convention) and can provide an estimate of remaining growth potential and help predict adult height.

Evaluating the pituitary gland with MRI may be indicated to rule out tumors and structural anomalies in suspected hypogonadotropic hypogonadism.

Genetic testing

About one third of cases of hypogonadotropic hypogonadism are genetic, and Kallman syndrome is the most common cause (see Secondary hypogonadism Secondary hypogonadism Male hypogonadism is decreased production of testosterone, sperm, or both or, rarely, decreased response to testosterone, resulting in delayed puberty, reproductive insufficiency, or both. Diagnosis... read more ). If other pituitary hormone deficiencies are noted, specific genetic abnormalities may be present (eg, PROP1).

Treatment of Delayed Puberty

  • Hormone therapy

If boys show no sign of pubertal development or of skeletal maturation beyond 11 to 12 years by age 14, they may be given a 4- to 6-month course of low-dose testosterone enanthate or testosterone cypionate 50 to 100 mg IM once/month. These low doses induce puberty with some degree of virilization and do not jeopardize adult height potential. After the course is complete, treatment is stopped and after several weeks or months testosterone levels are measured; an increase to pubertal levels suggest the deficiency was temporary rather than permanent. If testosterone levels are not higher than the initial value and/or pubertal development does not continue after completion of treatment, a second course of low-dose treatment can be given. If endogenous puberty has not begun after two courses of treatment, the likelihood of permanent deficiency is higher, and patients need to be reevaluated for other causes of hypogonadism. For permanent forms of hypogonadism, the testosterone dose is increased over an 18- to 24-month period towards adult replacement doses (see treatment of male hypogonadism in children Treatment Male hypogonadism is decreased production of testosterone, sperm, or both or, rarely, decreased response to testosterone, resulting in delayed puberty, reproductive insufficiency, or both. Diagnosis... read more ).

In girls, depending on the cause, hormone therapy may be used to induce puberty or, in some cases (eg, Turner syndrome), may be needed for long-term replacement. Estrogen replacement is given in the form of pills or patches, and the dose is increased over an 18- to 24-month period. Girls can be transitioned to combined estrogen-progestin oral contraceptive preparations for long-term treatment.

Key Points

  • Delayed puberty may represent constitutional delay or be caused by a variety of genetic or acquired disorders.

  • Measure levels of testosterone or estradiol, luteinizing hormone, and follicle-stimulating hormone.

  • Do a bone age x-ray as part of initial evaluation.

  • Pituitary imaging and genetic testing may be done to diagnose cause.

  • Hormone therapy may be indicated to induce puberty or as long-term replacement.

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