Which of the following best represents the occurrence of the adolescent growth spurt?

Central Nervous System and Puberty

Two independent but associated processes (controlled by different mechanisms but closely linked temporally) are involved in the increased secretion of sex steroids in the peripubertal and pubertal periods. In the first process, adrenarche, the increase in adrenal androgen secretion301,325 precedes by approximately 2 years the second process, gonadarche, which is a consequence of the pubertal reactivation of the hypothalamic-pituitary gonadotropin-gonadal apparatus.290,325,326

The onset of puberty is a consequence of maturational changes, including the development of secondary sexual characteristics, the adolescent growth spurt, the attainment of fertility, and psychosocial changes, all emanating from the disinhibition or reaugmentation of the hypothalamic GnRH pulse generator and gonadotropin secretion, causing an increase in gonadal steroid secretion256,327 (Table 26.10). The events characterizing the development of gonadal function can be viewed as a continuum extending from sexual differentiation and the ontogenesis of the hypothalamic-pituitary gonadotropin-gonadal system during fetal life and early infancy,126,254,326,327 through a juvenile pause (in which the system is suppressed to a low level of activity,326 discussed later), to the attainment of full sexual maturation and fertility during puberty, leading to the ability to procreate (Fig. 26.21). In this light, puberty does not represent the initiation or first occurrence of pulsatile secretion of GnRH or pituitary gonadotropins but the reactivation or disinhibition of GnRH neurosecretory neurons in the medial basal hypothalamus and the endogenous, apparently self-sustaining oscillatory secretion of GnRH after the period of quiescent activity during childhood. An increase in the pulsatilerelease of GnRH heralds the onset of puberty in primates and other mammals.126,327,328 The CNS, and not the hypothalamic GnRH pulse generator, pituitary gland, gonads, or gonadal steroid target tissues, restrains activation of the hypothalamic-pituitary-gonadal system during the prepubertal years.

Certain CNS lesions involving the hypothalamus and nearby structures can advance or delay the onset of human puberty.256,326 CPP, including cyclic ovulation in girls and spermatogenesis in boys, can result from a variety of CNS disorders. Several regulatory systems control puberty (Fig. 26.22):

In primates, the neural component controlling gonadotropin secretion resides in the medial basal hypothalamus, including the arcuate region. There are about 1500 to 2000 transducer GnRH neurosecretory neurons, which are not segregated into a specific nucleus but are functionally interconnected. These GnRH neurons comprise the GnRH pulse generator, which drives and controls the pituitary gonadal components, stimulates the release of LH and FSH, and translates neural signals into a periodic, oscillatory chemical signal, GnRH, in a coordinated manner. These pulses appear to be generated by a propagated depolarization, the firing of action potentials in individual cells, and the resulting influx of calcium through L-type calcium channels.329

In response to the GnRH rhythmic signal, the pituitary gonadotrophs, which contain the seven-transmembrane domain Gs-coupled LH/hCG receptors (LHCGRs),330 release LH and FSH in a pulsatile manner. Each LH and FSH pulse is induced by a pulse of GnRH.

The gonads, which are modulated primarily by the amplitude of the gonadotropin pulse, transmit the episodic gonadotropin signal into pulsatile secretion of gonadal steroids.331

Abstract

Normal puberty is controlled by the higher centers of the central nervous system which regulate the activity of the hypothalamic–pituitary axis, which in turn stimulates the gonads to secrete sex steroids which bring about the physical changes of puberty. This physiology originates during the fetal stage and ends in senescence. Thus puberty represents one stage in the progression to reproductive maturity. The development of gonadotropin-releasing hormone agonists for delaying pubertal development in transgender youth was based on the normal physiology of the hypothalamic–pituitary–gonadal axis. This chapter outlines this basic control of the onset of puberty and physical changes of puberty, and briefly mentions abnormalities of puberty that may develop with a disturbance in the normal physiology.

Aberrations of Timing of Puberty

Delayed puberty, more common in boys than in girls, is usually assigned to boys when sexual development has not begun by age 14 years. The majority of boys with delayed development have a functional hypothalamic-pituitary disorder and family history of delayed puberty; eventually they attain full sexual maturation. Once initiated, puberty is normally completed within 4.5 years. There are many other causes of delayed puberty including genetics, drugs, chronic illnesses, and diseases of the hypothalamus and pituitary. Careful documentation of changing physical findings and measurement of serum LH, FSH, and testosterone concentrations may provide valuable clues to the beginning of puberty. An increase in testicular size to more than 3 mL usually heralds other signs of pubertal onset. Inquiring and testing for hyposmia or anosmia and other midline defects may indicate a common variant of congenital hypogonadotropic hypogonadism (Kallmann syndrome). The decision to institute early treatment depends on the perceived degree of psychological stress associated with the maturational delay. The major concern is early fusion of the epiphyses induced by treatment with testosterone, which compromises optimal height; however, with judicious dosing and monitoring of bone age, this is unusual. In adolescent boys with delayed puberty and low levels of gonadotropins, periodic withdrawal of treatment is used to determine whether spontaneous puberty has occurred. Many adult men diagnosed with and treated as adolescents for a presumed diagnosis of hypogonadotropic hypogonadism achieve normal reproductive function when they discontinue therapy.

Precocious puberty in boys is defined as the onset of pubertal (secondary sexual characteristics) development before 9 years of age. Sexual precocity can be subcategorized as central or true isosexual precocious puberty and pseudo–precocious (peripheral) puberty. Central or true precocious puberty is associated with increases in GnRH-stimulated LH and FSH secretion (hypothalamic-pituitary origin), whereas pseudo–precocious puberty is independent of GnRH stimulation of LH and FSH secretion. Central precocious puberty in boys is often associated with CNS disease (two thirds of boys), including hypothalamic tumors, cysts, inflammatory conditions, and seizure disorders. Diagnostic findings include sexual precocity, inappropriately elevated serum LH levels, and associated elevations of testosterone. Magnetic resonance imaging can localize most lesions. Another cause of central precocious puberty is human chorionic gonadotropin secretory germinomas (testicular, hepatic, hypothalamic, or pineal tumors). Pseudo–precocious puberty is characterized by increased testosterone with suppressed LH. Causes of pseudo–precocious puberty include congenital virilizing adrenal hyperplasia, testicular testosterone-secreting neoplasms. Constitutively active LH receptor mutations result in uncontrolled testosterone secretion (testotoxicosis). Treatment of true precocious puberty is removal or correction (with surgery or radiation therapy) of the CNS lesion, if possible, and treatment with GnRH analogues to temporarily suppress LH and FSH secretion. Treatment of pseudo–precocious puberty depends on the cause but includes glucocorticoids for congenital virilizing adrenal hyperplasia and ketoconazole (to suppress steroidogenesis), with or without antiandrogens (e.g., spironolactone, flutamide).

Puberty

Puberty, as the starting point for adolescence, is often thought of as very stressful. The physical changes are obvious, as is an increased sexual interest. Parents and teachers often attribute all behavioral changes to raging hormones, but the fact is that there are other social, and psychological factors that must be considered as well. Nevertheless, there is a biological effect of puberty on cognitive, social, and emotional development as well. In particular, the timing of puberty can be stressful and does seem to have an impact on academic and psychosocial functioning. Boys appear to benefit academically and socially if they reach puberty early, although they often end up having a shorter stature than their later-developing peers. Early in adolescence, girls seem to have a better body image and are more popular if they develop early. However, as a group, they do not seem to do as well academically. Furthermore, by the time adolescence ends, later developing girls have a better body image than girls who reached puberty earlier do.

This may be related to the fact that girls with a later onset of puberty are more slender, which more closely fits with current cultural standards of attractiveness. More importantly, girls who reach puberty later have had a longer time to anticipate and adapt to these changes and as a result seem better able to cognitively process and cope with pubertal changes when they do occur. Finally, puberty may be most stressful when it is very early or very late, as this leads the adolescent to be markedly different from other peers. This information coincides with Offer's reports that most adolescents are comfortable with, and not distressed by, the changes of puberty, as most adolescents will enter puberty at about the same time as their peers and experience it as a normative process.

Physical Changes at Puberty

Puberty extends from the earliest signs of sexual maturation until the attainment of physical, mental, and emotional maturity. Pubertal changes in girls result directly or indirectly from maturation of the hypothalamic-pituitary-ovarian (HPO) unit.1 Human puberty is characterized hormonally by a resetting of the negative gonadal steroid feedback loop, the establishment of new circadian and ultradian (frequent) gonadotropin rhythms, and the acquisition in the female of a positive estrogen feedback loop controlling the menstrual cycle as interdependent expressions of the gonadotropins and ovarian steroids. In girls, pubertal development generally occurs between 7 and 14 years of age. The age at onset and the rate of progress through puberty are variable and depend on genetic, socioeconomic, nutritional, physical, and psychological factors. It appears that there are racial differences in the onset of pubertal development. In the United States development begins earlier in African American than in white girls.

Physical changes occur in an orderly sequence during a definite time frame in puberty (Fig. 222-1). Breast budding in girls is usually the first pubertal change, followed shortly by the appearance of pubic hair, with menarche occurring late in pubertal development. The time from breast budding (mean age of 10.0 years in white girls and 8.9 years in African Americans) to menarche is 2 years. Breast development results from increasing ovarian estrogen production, and pubic and axillary hair results from increasing androgen production. Estrogens are required for the growth of pubic hair as well.

The ovarian sex steroids join with growth hormone and adrenal androgens to produce the adolescent growth spurt.2 Peak growth velocity is achieved relatively early, with little growth observed after menarche. It has been estimated that more than 50 genes play roles in determining final adult height. It is now clear that estrogen, and not testosterone, is the primary hormone mediating pubertal bone growth in both males and females. Lean body mass, skeletal mass, and body fat are equal in prepubertal boys and girls, but by maturity, women have twice as much body fat as men and less lean body mass and skeletal mass as a result of differences in sex steroid secretion. Estrogens are necessary for the normal formation, mineralization, and maturation of bones. Well-established standards exist for determining whether bone age is appropriate for chronologic age, typically by examining radiographs of the bones of the wrist. Estrogen deficiencies retard, and excesses advance, bone age in relation to chronologic age.3

Pubertal Development and Pubertal Timing

Puberty is associated with important developmental changes in physical appearance, self-image, mood, and interactions with others. Many of the changes associated with puberty are physical, and puberty naturally draws adolescents’ attention more to their own bodies and that of their peers. Pubertal development is usually a positive experience for boys, as the majority of boys move closer to the societal ideal shape for a man. Boys add muscle and their shoulder width increases, which are physical characteristics that fit the ‘ideal’ cultural ideal for male’s body shape and size. However, several studies have not found a direct association between puberty and body image concerns among boys.

The inconsistencies across the studies may be due to the timing of pubertal development, and the interplay between puberty, psychosocial development, role expectations, and social pressures that undergo marked changes during the adolescent years. For example, during the transition to puberty, boys have been found to have higher depressive symptoms than postpubertal boys, and these symptoms are directly associated with boys’ perceptions that they are not as physically large and developed as their peers.

Although puberty is experienced by all adolescents, the timing may differ considerably. In fact, the actual timing of puberty in relation to one’s peers has been shown to be more important than pubertal development per se. From a developmental perspective, experiencing puberty prior to and later than one’s peers can be associated with feelings of alienation and depression. This has been described as ‘the off-time hypothesis’, and it maintains that both early and late maturing adolescents will manifest more social, emotional, and behavioral problems than their on-time age-mates. The off-time hypothesis has been more fully described in the case of early maturing girls, but there is increasing evidence that it also holds for late maturing boys. Several studies have linked late maturation in boys with less social competence, low peer popularity, more conflict with parents, more internalizing tendencies, more drinking problems, and lower school achievement.

Puberty Defined

Physiologically, puberty is a short-term event (taking place over a few weeks) of the central nervous system, which reinitiates positive feedback within the hypothalamic–pituitary–gonadal (HPG) axis and promotes sexual maturation. Puberty is also defined socially, to mean the period of time when sexual development and its related behaviors and emotions are taking place. In this article, we use the physiological definition for puberty and use the term ‘adolescence’ to refer to the period of time for sociosexual maturation between puberty and adulthood.

The hormonal agents

Puberty is a product of the human hormonal system. While virtually all hormonal structures activate and change during adolescence, three important hormonal axes determine the puberty metamorphosis, including the hypothalamic-pituitary-gonadal (HPG) axis, the hypothalamic-pituitary-adrenal (HPA) axis, and the growth hormone (GH) axis (Carswell & Stafford, 2016; Lee & Styne, 2012).

The HPG axis reaches maturation during puberty and is responsible for sexual development, thelarche (onset of breast development) and menarche (onset of menses) through the release of estradiol [E2 (estrogen)] from the ovary and testosterone (T) from the testes, respectively (Carswell & Stafford, 2016; Lee & Styne, 2012). Independent of the HPG axis, the HPA axis oversee the production of androgens from the adrenal glands, leading to the growth of terminal hair in the axillary and pubic areas, development of body odor, and increased sebum production and development of acne (Carswell & Stafford, 2016). As its name suggests, the GH axis—coupled with sex steroids—is responsible for growth spurts during puberty, including bone and muscle growth (Carswell & Stafford, 2016).

Abstract

Puberty, which in humans is considered to include both gonadarche and adrenarche, is the period of becoming capable of reproducing sexually and is recognized by maturation of the gonads and development of secondary sex characteristics. Gonadarche referring to growth and maturation of the gonads is fundamental to puberty since it encompasses increased gonadal steroid secretion and initiation of gametogenesis resulting from enhanced pituitary gonadotropin secretion, triggered in turn by robust pulsatile GnRH release from the hypothalamus. This chapter reviews the development of GnRH pulsatility from before birth until the onset of puberty. In humans, GnRH pulse generation is restrained during childhood and juvenile development. This prepubertal hiatus in hypothalamic activity is considered to result from a neurobiological brake imposed upon the GnRH pulse generator resident in the infundibular nucleus. Reactivation of the GnRH pulse generator initiates pubertal development. Current understanding of the genetics and physiology of the brake will be discussed, as will hypotheses proposed to account for timing the resurgence in pulsatile GnRH and initiation of puberty. The chapter ends with a discussion of disorders associated with precocious or delayed puberty with a focus on those with etiologies attributed to aberrant GnRH neuron anatomy or function. A pediatric approach to patients with pubertal disorders is provided and contemporary treatments for both precocious and delayed puberty outlined.

Puberty

Puberty represents the ‘start’ of adolescence, the onset of sexual maturation, and major changes in the neuroendocrine axes. Starting in the hypothalamus, moving to the pituitary, and then onto the periphery, hormones, such as dehydroepiandrosterone, cortisol, estrogen, and testosterone, all surge during puberty. Such changes may directly or indirectly influence emotional states through rising hormone levels, alterations in the brain's emotional circuitry, or increasing psychosocial challenges associated with a changing behavioral repertoire. Puberty is an important developmental event especially in regard to emotion regulation, as puberty has been linked with changes in arousal and motivation, behavioral adaptation, and vulnerability to psychopathology.

Many aspects of arousal, motivation, and emotion have been linked with pubertal maturation (as opposed to age). For example, adolescents in more advanced stages of puberty seek out excitement and stimulation and may engage in more dangerous behaviors compared to adolescents at earlier stages of puberty. Interestingly, similar trends have been noted in a wide variety of nonhuman animal species, as a natural increase in exploratory and reward-seeking behavior is seen at puberty. In terms of emotions, pubertal development seems to be associated with the functioning of emotional relationships, such as the development of romantic interest and sexual motivation along with increasing parent–adolescent conflict. Variations and early timing in pubertal onset have also been associated with increased moodiness and negative affect such as anger, frustration, aggressive behavior, and delinquency.

Recent research has also found that laboratory studies of emotion regulation are related to pubertal status. For example, adolescents at more advanced pubertal stages show greater emotional reactivity, remember more emotional words, and have higher eye-blink startles compared to less pubertally advanced children. With the strengthening connection between emotional processes and variations in puberty, it is not surprising that emotional dysregulation and increased rates of psychopathology have been associated with aberrant pubertal processes. Pubertal stage has been strongly associated with anxiety and depression, eating disorders, and substance abuse.

Importantly, these effects may or may not be directly a result of rising hormones. Initial research examining the role of pubertal hormones on psychopathology failed to find a relationship between gonadal steroids and depressive symptoms. However, a more recent population-based study found a linear relationship between gonadal steroids (e.g., estrogen or estrogen + testosterone) and symptoms of depression in a large sample of adolescent girls. Many have asserted how gonadal hormones, such as estrogen, testosterone, or DHEA may affect important neurochemical systems involved with affective psychopathology such as γ-aminobutyric acid (GABA), serotonin, and/or dopamine. Alterations in dopamine near puberty may be particular important, as this neurotransmitter has been implicated in motivation and reward, mood, attention, and learning.

Turning to gender differences, research has linked aberrant pubertal development to different outcomes in girls compared to boys. For example, early maturation has been linked to body dissatisfaction, increased rates of self-reported psychological distress and negative mood, and also more psychopathology such as depression in girls. Late maturing girls also have increased social problems. In males, this relationship is more complicated, as early pubertal development has been associated with increased aggression, deviant behavior, and psychopathology. However, earlier timing and advanced pubertal development have also been linked with positive outcomes, such as enhanced self-esteem and body image, and decrease in social problems and attention problems.

In sum, the research reviewed here details the emerging link between emotion dysregulation and pubertal variations. However, there are many major unanswered questions. In particular, the role of intermediary factors and interactive effects is still not clear. For example, one study found that early pubertal maturation did not put girls at risk for increased behavioral problems, but rather it was the interaction of behavioral problems prior to entry into puberty and early timing which was related to increasing behavioral problems. Other studies have found that pubertal status interacts with emotional state in predicting emotional reactivity. In addition, inconsistencies still exist in the literature. As detailed earlier, risk taking, sensation seeking, and novelty seeking are correlated more strongly with puberty than age; while at the same time, levels of fear and emotional reactivity also increase at puberty. Finally, little research in humans has examined exactly how puberty may affect brain development. This area of study is critical to understanding the effects of puberty on behavior, as many gonadal hormones modulate the development of the prefrontal cortex, hippocampus, and amygdala.