(See also puberty in males Sexual Differentiation, Adrenarche, and Puberty Male sexual development and hormonal function depend on a complex feedback circuit involving the hypothalamus-pituitary-testes modulated by the central nervous system. Male sexual dysfunction... read more , puberty in females Puberty Hormonal interaction between the hypothalamus, anterior pituitary gland, and ovaries regulates the female reproductive system. The hypothalamus secretes a small peptide, gonadotropin-releasing... read more , and constitutional delay of puberty Secondary hypogonadism .)
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 
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 
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 
), 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).
Neurologic symptoms (eg, headaches, vision problems), polydipsia, and/or galactorrhea Galactorrhea Galactorrhea is lactation in any men or in women who are not breastfeeding. It is generally due to a prolactin-secreting pituitary adenoma. Diagnosis is by measurement of prolactin levels and... read more could suggest a CNS disorder. Hyposmia or anosmia Anosmia Anosmia is complete loss of smell. Hyposmia is partial loss of smell. If unilateral, anosmia is often unrecognized. Most patients with anosmia have normal perception of salty, sweet, sour, and... read more could indicate Kallman syndrome.
Gastrointestinal symptoms could suggest an inflammatory bowel disorder 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 . An abnormal body image (eg, false belief in being overweight) suggests the need to evaluate for an eating disorder 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 .
Primary amenorrhea Evaluation of primary amenorrhea [a] ![Evaluation of primary amenorrhea [a]](/-/media/manual/professional/images/g/y/n/gyn_primary_amenorrhea_algorithm_no_fnts_change.gif?sc_lang=en&mh=160&mw=160)
could suggest 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 .
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] ).
Elevated serum LH and FSH levels indicate
Gonadal failure caused by defects of the gonads themselves ( primary hypogonadism Primary 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 [hypergonadotropic hypogonadism])
In such cases, karyotype analysis should be done to investigate for 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 in boys and Turner syndrome Diagnosis 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 in girls. If karyotype is normal, girls with severe pubertal delay should be further investigated for other causes of primary ovarian insufficiency Diagnosis In primary ovarian insufficiency, ovaries do not regularly release eggs and do not produce enough sex hormones despite high levels of circulating gonadotropins (especially follicle-stimulating... read more .
Low FSH and LH levels along with low testosterone and estradiol levels in children with short stature and delayed pubertal development may indicate
Constitutional delay
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.
