Sasha Lu

Puberty is the normal physical transitional process that leads to reproductive maturity. Precocious affects about 1% of children in the US with most cases being a variant of normal. [Eugster: 2006] Delayed puberty is estimated to occur in about 3% of children with most being constitutional delay. Children with special health care needs can have increased risk of either early or delayed puberty and evaluation may be necessary to determine the cause and potential need for intervention. This page provides guidance for clinicians about puberty-related topics that are addressed in the medical home.

Definitions

• Adrenarche: Often used synonymously with pubarche - a detectable increase in the secretion of adrenal androgens (may occur years before pubarche)
• Gonadarche: Onset of puberty due to activation of hypothalamic-pituitary-gonadal (HPG) axis
• Gynecomastia: Growth of glandular breast tissue in males
• Menarche: Onset of menstruation
• Pubarche: Onset of pubic hair development
• Puberty: Onset of secondary sexual characteristics
• Thelarche: Onset of breast development
• Sexual maturity rating, or Tanner staging: System of assessing physical characteristics during sexual maturation. See excerpt from AAP’s Bright Futures Pocket Guide

Puberty usually starts between the ages of 8-13 for girls and 9-14 for boys with some variations based on family/genetic factors, nutritional status, race, and ethnicity. Some consider the onset of breast development and pubic hair in girls at ages 7 or 8 to be the new lower limit of normal because 15-20% of African American girls and 5-10% of Caucasian girls (and Hispanic in between) develop 1 or both of these signs by 7-8 years. [Hillard: 2013]

Gonadarche is the onset of central puberty leading to production of sex steroids by the ovaries (estrogen) or testes (testosterone). It is NOT defined by isolated pubic hair, axillary hair, body odor, or acne. [Palmert: 2012] These isolated signs can be related to adrenal androgen secretion (as discussed in adrenarche section) and develop independently from the hypothalamic–pituitary–gonadal (HPG) axis.

• Pubertal changes in girls: thelarche, pubarche, growth, and menarche
• Pubertal changes in boys: testicular enlargement, pubarche, and growth

The primary care clinician should watch for early or late development of secondary sexual characteristics and provide relevant anticipatory guidance and medical care including appropriate evaluations and referral. Children with obesity may start puberty earlier (more often seen in girls) or later (more often seen in boys) than children with a normal body mass index. [Kleber: 2011] [Rosenfield: 2009]

Early (precocious) puberty is classically defined as the onset of secondary sexual characteristics tempered by the family history of maturation patterns. For girls, these changes include breast development or pubic or axillary hair before age 8 (as discussed in Normal Puberty, above, the age may be slightly younger than 8). For boys, these changes include testicular, scrotal, or penile enlargement and pubic or axillary hair before the age of 9. Precocious puberty can lead to more rapid growth, advanced bone age, and early fusion of growth plates leading to reduced adult height, as well as behavioral issues relating to early body maturation and sexual development. [Berberoğlu: 2009]

If concern for precocious puberty arises, the clinician must consider whether the change is due to a benign variant (e.g., isolated premature thelarche or adrenarche) or a central (intracranial mass or idiopathic) or peripheral (adrenal or gonadal) cause. Benign pubertal variants can be followed in the medical home; refer to endocrinology (see below) for evaluation and treatment of precocious puberty when there are concerning signs.

Algorithms to help clinicians evaluate girls and boys with early onset of secondary sexual characteristics: [Berberoğlu: 2009]

• Early Breast Development in Girls
• Early Genital Development in Boys

While pelvic ultrasound is included in the evaluation algorithm of early breast development in girls, the involvement of a technician and radiologist experienced with pediatrics is strongly advised.

Premature Thelarche

Premature Adrenarche

• Girls with premature adrenarche have increased risk of polycystic ovary syndrome, insulin resistance, and metabolic syndrome in late adolescence. [Oberfield: 2011]
• Severe acne, hirsutism, linear growth spurt, or enlarged clitoris or penile length, or increased testicular volume would merit additional workup in consultation with a pediatric endocrinologist. [Hillard: 2013]

Delayed puberty is classically defined as absence of thelarche in girls at age 13, absence of menarche within 4 years of thelarche, or lack of testicular enlargement in boys at age 14. [Palmert: 2012] By far, the most common cause of delayed puberty is constitutional growth delay, which is a diagnosis of exclusion. An individual with delayed puberty is often referred to as a “late bloomer.” [Palmert: 2012]

Diagnosis & Evaluation

• Labs to consider: First morning LH, FSH, estradiol (girls) or testosterone (boys), TSH +/- free T4, bone age. Karyotype, especially in girls with delayed puberty along or in conjunction with short stature to evaluate for Turner Syndrome
• Family history of age at onset of puberty/menarche, heights of biological parents
• History of CNS or gonadal insults, including trauma, infection, irradiation, or chemotherapy
• Pubertal exam: Palpable breast tissue in girls and testicular volume >3mL indicates onset of puberty
• Evaluate growth rate. Normal prepubertal growth rate in childhood is 4-7cm/year.
• Evaluate weight gain/nutritional status. Underweight children are at risk of delayed puberty.
• Examine for signs of genetic syndromes associated with delayed puberty, such as Klinefelter, Turner, Prader-Willi, Noonan and other rare syndromes

Differential Diagnoses

• Constitutional delay
• Functional hypogonadotropic hypogonadism: Underlying chronic disease, severe emotional stress, malnourished
• Hypogonadotropic hypogonadism (low LH, FSH, sex hormone): Prader Willi Syndrome, Noonan syndrome, CNS lesions
• Hypergonadotropic hypogonadism (high LH, FSH, and low sex hormone): Testicular failure including Klinefelter syndrome, testicular injury/infection, ovarian failure including Turner syndrome, primary ovarian failure due to autoimmunity

Management

• Constitutional delay: Observation is most common; consider referral for possible treatment after a complete workup has been performed if there are significant psychosocial stressors.
• Hypogonadotropic and hypergonadotropic hypogonadism: Hormone replacement aimed at mimicking normal physiology exam

Breast development in boys is common and usually benign. There are several types:

• Lipomastia (pseudogynecomastia): Excess adipose tissue in breast area without true glandular breast tissue that is distinguishable only by palpation
• Infantile gynecomastia: Same mechanism of premature thelarche in infant girls and typically resolves in a few months, but it may persist up to 12 months
• Physiological pubertal gynecomastia presents in boys in sexual maturity rating/Tanner stage 3-4 (ages 13-14 years is the peak) and has an incidence as high as 50%. The mechanism in adolescents is caused by a relative imbalance of estrogen to testosterone, which leads to preferential estrogen effects until later in puberty when androgens/testosterone levels rise further. Typical resolution occurs within 1-3 years in 90% of boys.
  • More common in obese males – increased aromatization of androgens to estrogen by fat tissue
• Pathologic gynecomastia: Possible causes include:
  • Increased estrogen from tumors (germ cell, Sertoli cell and Leydig cell, liver, and adrenal), drugs, substance abuse, hyperthyroidism, liver dysfunction, exogenous estrogen, or increased aromatase [Diamantopoulos: 2007]
  • Decreased androgens from primary gonadal dysfunction, androgen insensitivity, or problems with testosterone synthesis
• Idiopathic gynecomastia mostly occurs in puberty or adulthood; however, it can occur before puberty in some. It is a diagnosis of exclusion and usually a benign condition, but psychological and cosmetic concerns may arise in some males. [Diamantopoulos: 2007]
  • Presence of obesity increases risk

Diagnosis & Evaluation

• Labs to consider: Workup (LH, FSH, estradiol, testosterone, DHEAS, bHCG, LFTs ) for gynecomastia in prepubertal boys when there is rapid progression or nipple discharge
• Assessment for abnormal growth patterns, eunechoid habitus, developmental delays, vision defects, neurological deficits, liver mass or abdominal mass
• Palpation of the tissue (asymmetric or unilateral common), pubertal exam
• Testicular exam: Look for testicular volume that is discrepant with sexual maturity rating/ Tanner stage or difference between testicles.

Co-occurring Conditions

• Hypogonadism can occur in Klinefelter syndrome in association with a characteristic phenotype (sparse facial/pubic hair, eunuchoid body habitus) and behavioral problems.

Management

• Physiological pubertal gynecomastia: Since most spontaneously resolve, no treatment is necessary. Cosmetic surgery is an option for particularly large/bothersome breast tissue.

Infant girls may have spotting of blood (like a “mini-period”) and discharge after birth, known as neonatal withdrawal bleeding. Other causes of prepubertal girls can be trauma, foreign bodies, infection, urethral prolapse, or abnormalities of the vagina or uterus. Recurrent/cyclic vaginal bleeding, or premature menarche, is rare.

Diagnosis & Evaluation

• Labs to consider: LH, FSH, estradiol, bone age as well as a pelvic ultrasound to investigate for tumors or ovarian cyst [Long: 2015]
• Young girls may have 1-2 occasions of vaginal bleeding without any other clinical signs of precocious puberty. They have a normal prepubertal evaluation. [Kaplowitz: 2016]

Co-occurring Conditions

• McCune-Albright syndrome, acquired central precocious puberty, or severe primary hypothyroidism

Management

• For isolated prepubertal vaginal bleeding that occurs after the first 1-2 weeks of life, a good history and physical examination are necessary.
• Consider consultation with a pediatric gynecologist to evaluate and manage structural causes.
• For cyclic vaginal bleeding, consult with a pediatric endocrinologist to identify and address the underlying cause.

Many children with chronic medical conditions undergo pubertal development at approximately the same age as typically developing children, but there is often more variation in the onset, rate, and duration of this process.

• Children born small for gestational age have a tendency for earlier pubarche and faster progression of puberty when compared to children born average for gestational age. [Verkauskiene: 2013]
• Children with cerebral palsy may start into puberty earlier than typically developing children and take slightly longer to reach full pubertal development. [Worley: 2002]

Delayed pubertal development is often given less priority when a child has severe impairments; however, the lack of pubertal development may be a sign of underlying pathology that needs treatment (e.g., malnutrition, thyroid dysfunction, pituitary adenoma). In cases of hypogonadism, intervention will depend on the particular situation.

Pubertal development is essential for normal bone health in both males and females. Estrogen or testosterone deficiency places a child at risk for pathologic fractures so must be addressed.

Menstruation