Puberty is a vital process in the development of all individuals. The series of hormonal changes during puberty result in the physical development of sexually mature adults. In addition to sexual maturity children also go through other physical and emotional changes such as hair growth, voice changes, and acne. In this article the development, organ systems involved, physiological mechanism, evaluation and testing, pathophysiology, and clinical significance of puberty will be discussed.
GnRH neurons of the hypothalamus control the initiation of puberty. The pulsatile secretion of GnRH by these neurons causes the changes of puberty. Currently, there are increasing amounts of evidence showing that kisspeptin neurons in the arcuate nucleus release neurokinin B and dynorphin to generate the pulsatile secretion of GnRH. GnRH causes the release of LH and FSH from the gonadotropic cells of the anterior pituitary gland. FSH and LH affect the Leydig and Sertoli cells in the testes and the theca and granulosa cells of the ovary. The zona reticularis of the adrenal cortex produced the hormones responsible for adrenarche and function separately from the hypothalamic-pituitary-gonadal axis.
Puberty typically begins around 6 for African American girls and 7 years of age in white girls but can range between 8 and 13 years of age. The first sign of puberty is linear growth, but examiners do not usually notice this growth. The most notable and reliable first sign of puberty in girls is breast development. Other signs of puberty include enlargement of the labia majora and labia minora and clear to white vaginal discharge. The pubertal growth spurt occurs between 9 and 10 years old. Breast development (thelarche) typically occurs between 8 to 12 years old with a mean age of 10 years old. Menarche follows shortly after thelarche about 2.5 years later with a mean age of 12.5 years but can range from 9 to 15 years old. Pubic hair development usually follows along with breast development and occurs due to the production of adrenal androgens. Production of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) by the adrenal gland increases around age 6 to 7 years and is independent of thelarche and menarche. DHEA and DHEAS influence pubic hair development as well as axillary hair development and body odor. Tanner staging is the best way to assess the stage a child may be in; the categorization of each stage can be seen in Table 1.
Puberty in boys begins with testicular enlargement to greater than 2.5 cm in length or greater than 4 mL in volume; this occurs between 9.5 and 14 years of age with an average of 11.5 years of age. Pubic hair development in males is controlled by both adrenal androgens DHEA and DHEAS as well as androgens produced by the testicles, and usually occurs between 7 and 8 years old. These androgens also assist in the development of axillary and facial hair, and voice changes. Male growth spurts typically occur between 11 and 12 years old. Other pubertal changes seen in males include a decrease in total body fat, voice break and change, and an increase in muscle mass. The different stages of pubertal development and what qualifies for each stage can be seen in Table 2.
The reproductive system is the main organ system involved in puberty. The changes of puberty allow the reproductive system to become fully functional. By the end of puberty, both males and females are fertile and able to reproduce. The endocrine system is the other major role player in puberty. The hypothalamus, pituitary gland, adrenal glands, ovaries, and testes all produce hormones involved in the changes of puberty. The hormones produced affect multiple systems within the body. The specific hormones and their involvement in the process of puberty are discussed further in the mechanism section.
The main function of puberty is to produce sexually mature adults. The hormonal changes of puberty allow children to become reproductively viable. Puberty is also a period of increased linear growth; a large portion of an individual’s height is achieved from the growth occurring in puberty.
The mechanism of the initiation of puberty is not entirely understood; however, it is known that the GnRH neurons are the primary role player in the initiation of puberty. The GnRH neurons develop in the olfactory placode and then migrate to the area of the hypothalamus during the gestational period. Puberty begins with the pulsatile secretion of GnRH from these neurons, other neurotransmitters, GABA and NMDA, are also linked with this process. Additionally, the genes KISS1 and neurokinin B have recently been shown to be involved in the regulation of GnRH release. The increased levels of GnRH increase the release of LH and FSH from the anterior pituitary. During puberty, the negative feedback mechanism is less sensitive allowing for higher levels of FSH and LH to circulate within the body. FSH increases estrogen production by the ovaries in girls, and in boys triggers testicular growth and supports maturing spermatozoa. LH initiates ovulation and creates the corpus luteum in females, and in males acts on Leydig cells in the testes to increase testosterone production. The Increased production of adrenal androgens leading to the development of acne, axillary hair, body odor, and pubic hair is also taking place during the onset of puberty. The linear growth seen in puberty is a result of pulsatile increases in growth hormone (GH) secretion, which is secreted by the pituitary gland. Increases in insulin-like growth factor 1 are also present. Estrogen increases the rates of GH secretion and is involved in growth plate acceleration and fusion. Testosterone increases insulin-like growth factor 1 levels and bursts of GH secretion.
The first-line assessment for any child experiencing issues with pubertal development is a thorough history and physical exam. The history will allow the healthcare practitioner to gain insight as to if there is any possibility of a genetic cause. The history will also provide vital information about the child’s growth pattern and development to date. In addition, it may also point out clues to other causes of pubertal disorders such as poor nutrition, underlying disease, excessive exercise, or the use of exogenous steroids. The physical exam should include an examination of the genitalia and the breasts in girls to determine tanner staging. Tanner staging is a standard system used to categorize the different stages of pubertal development a child has achieved. For boys, Tanner staging includes testes and penile growth, pubic hair distribution, and linear growth. In girls, Tanner staging includes breast development, pubic hair distribution, and linear growth. In addition to tanner categorizations examination of the optic fundus and determining if the sense of smell is intact can be helpful. Standardized growth charts tracking the child’s growth over time are also helpful in determining if a child is developing appropriately. Skin lesions noted on the physical exam can also point toward certain causes of abnormal puberty such as McCune-Albright Syndrome. An x-ray of the left wrist is commonly used to determine bone age and whether the child’s bone maturation is more advanced than their age, suggesting they might be going through premature puberty. In addition to an x-ray of the left wrist, central nervous system (CNS) imaging may be performed if there are signs of CNS involvement. Measurement of hormone levels may also be helpful in the presence of abnormal puberty. Levels of estradiol, testosterone, FSH, and LH can be measured looking for pubertal or prepubertal levels. A GnRH stimulation test is also helpful to determine a central or peripheral cause. The test involves the administration of 100 micrograms of GnRH after overnight fasting and observing the levels of FSH, LH, estradiol, and testosterone at 15, 30, 45, and 60 minutes post-injection. The stimulation test will cause activation of the hypothalamic-pituitary-gonadal axis in central causes resulting in increased levels of the hormones, a peripheral cause will not increase hormone levels. Additional testing that may be done includes, thyroid hormone levels (TSH, T3, T4), blood glucose levels, a complete blood count, liver enzymes, and an erythrocyte sedimentation rate. Another type of testing that can be done is a karyotype which will show the child’s chromosomal pattern and is helpful if there is a suspicion of Turner or Klinefelter’s syndrome. Although there are many other factors that could be evaluated after a history and physical the testing should be tailored individually for each child’s presentation and towards the most likely cause of their abnormal puberty.
The pathophysiology of puberty can be broken down into 3 main categories premature puberty, delayed puberty, and contrasexual development.
Precocious puberty or early development of secondary sexual characteristics is defined as pubertal development before age 6 in African American girls and before 7 years in all other girls; however, an age of anything younger than 8 years is also used. Precocious puberty is defined in boys as the development of secondary sexual characteristics before age nine. Many of the causes of early pubertal development are shared however there are some causes of early puberty unique to each of the sexes.
The causes of precocious puberty shared by either gender include benign premature adrenarche, central nervous system and pituitary lesions, constitutional and idiopathic precocious puberty, McCune-Albright syndrome, and exogenous sex hormones.
Premature adrenarche correlates with the premature presence of pubic or axillary hair and possibly increased sebaceous gland activity without other signs of puberty present, usually before 6 years of age. This is usually an isolated abnormality, and most children go on to develop the other signs of puberty at a normal age. Plasma DHEAS is usually elevated to pubertal levels. Other sex hormones such as FSH, LH, estradiol, and testosterone are typically at levels found in children before puberty. Other studies such as a GnRH stimulation test will show prepubertal results, and an ACTH stimulation test may be used to exclude congenital adrenal hyperplasia which can have similar presenting symptoms.
CNS and pituitary lesions will typically present with normal stages of puberty but occurring prematurely. Children may have a bone age greater than their chronological age. Additionally, these lesions may come with other problems such as visual field defects. If a central nervous system lesion or a pituitary lesion is suspected, an MRI of the brain can determine the presence of a lesion in these areas.
Constitutional/idiopathic precocious puberty tend to present more often in females but can occur in both boys and girls. Precocious or premature puberty is considered idiopathic when a child has no familial links to premature development and there is no other cause that can be found for the premature development of puberty. Constitutional precocious puberty can be linked to a familial tendency toward early development. Children with these disorders will respond to a GnRH stimulation test with pubertal levels of sex hormones as well as FSH and LH. These children may have a bone age that is much higher than their chronological age. Additionally, all other causes of premature puberty must be ruled out such as CNS pathology and elevated adrenal hormones.
McCune-Albright syndrome is associated with cafe-au-lait spots, polyostotic fibrous dysplasia, and precocious puberty. McCune-Albright syndrome is also associated with other endocrine disorders. The cafe-au-lait spots can be large and have been described as resembling the coast of Maine.
Exogenous sex hormones in substances such as oral contraceptives and anabolic steroids can cause secondary sexual characteristics to develop. These causes can usually be ruled in or out as a cause rather quickly by running a urinalysis. The metabolites of exogenous hormones can be found in the urine. Additionally, children who have an exogenous hormone source and are not undergoing natural puberty will lack pubic hair. Girls may have darkened areolae, and boys will have small testicles of a prepubertal child.
Causes of premature puberty unique to males include gonadotropin secreting tumors, benign gynecomastia of adolescence, and familial gynecomastia.
The causes of the signs of premature puberty unique to females include premature menarche, and premature thelarche.
Delayed puberty is the lack of physical evidence of puberty by 2 to 2.5 standard deviations above the mean age for the initiation of puberty. In boys, this is considered a period longer than four years between the first signs of testicular enlargement and the end of puberty, or the absence of testicular growth by 14 years old. Delayed puberty in girls is considered the absence of breast growth by 13 years old or more than four years between thelarche and menarche. The causes of delayed puberty include hypogonadotropic hypogonadism, hypopituitarism, constitutional delay, chromosomal abnormalities, and hypothalamic dysfunction due to secondary causes.
Contrasexual development occurs when male or female children develop physical features of the opposite gender. This condition tends to be more common in girls and is commonly caused by polycystic ovaries and increased responses by the adrenal gland. Girls will have a male like distribution of hair and may develop hirsutism. Girls can also develop clitoromegaly and lose contour of the breast mass. The possible causes include Cushing syndrome, acromegaly, exogenous androgens, adrenal tumor, ovarian tumor, and hyperprolactinemia. Although contrasexual development is less common in boys, the cause is typically estrogen-secreting tumors.
Puberty is an extremely significant process and a part of all children’s development into functional adults. During this time children begin to gain the capacity for reproduction, which is essential to discuss with children as they progress through puberty. Discussion of sexual practices is an important aspect of well-child visits and is pertinent to identify children that may be having unsafe or high-risk sexual encounters. The discussion of the sexuality by pediatricians or other medical caregivers with young teens as they progress into adulthood provides a chance for them to speak to someone under confidentiality and ask specific questions to understand better their sexuality as well as what is considered safe sexual practices. Puberty also coincides with a child’s psychosocial development. Children who may be early or behind in attaining the milestones of puberty in comparison to their peers are at a much higher risk of emotional distress and low self-esteem. The ability to monitor the progression of puberty in the pediatric population is vital as it is essential to their reproductive development but also because of the many physical and psychological risks children face during this time in their development.