Medical Physiology, 3rd Edition


Although at birth humans have the primary and secondary sex organs necessary for procreation, final sexual maturity occurs only at puberty, the transition between the juvenile and adult states when an individual becomes capable of reproducing.

Puberty involves steroid hormones produced by the gonads and the adrenals

Puberty involves two physiological processes: (1) gonadarche, the physical and functional maturation of the gonads, such that they produce gametes and sex steroids; and (2) adrenarche, the increased production of the androgenic steroids dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione (A4) by the adrenal cortex (see Fig. 50-2). Adrenarche is peculiar to humans and great apes and occurs in both sexes during the prepubertal period (ages 6 to 8 years). The increased levels of adrenal androgens induce pubarche, the growth of pubic hair. The function of adrenarche is unclear, inasmuch as its absence does not prevent gonadarche or the attainment of reproductive competence. The mechanisms that control the timing of adrenarche are also not known.

Gonadarche is induced by increased production of the gonadotropic hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary (see pp. 1094–1095 and 1111–1112). Although a surge in levels of the pituitary gonadotropins occurs during intrauterine life and a second peak takes place in the immediately postnatal period, gonadotropin levels decrease at ~4 months of age and thereafter decline further and remain low until just before puberty. At puberty, the marked increase in FSH and LH production by the hypothalamic-pituitary axis induces gonadarche. The gonadal steroids produced in response to FSH and LH induce growth and maturation of the genitals and secondary sex organs and the development of secondary sex characteristics. The gonadal steroids also participate (with growth hormone and insulin-like growth factors) in the adolescent growth spurt. In males gonadarche leads to spermarche, the initiation of sperm production by the testes (see p. 1092), and in females it leads to folliculogenesis and menarche, the initiation of menstrual cycles, and thelarche, development of breasts (see p. 1108).

Hypothalamic gonadotropin-releasing hormone secretion controls puberty

Gonadotropin production by the anterior pituitary is under the control of gonadotropin-releasing hormone (GnRH), produced by neurons in the hypothalamus (see pp. 1092–1094 and 1111). The activity of hypothalamic GnRH neurons is controlled by higher centers in the brain that integrate multiple physiological signals. One of the earliest events of puberty in males and females is the onset of pulsatile release of GnRH from the hypothalamus and, in turn, FSH and LH from the anterior pituitary, during rapid eye movement sleep. These pulses eventually occur throughout the day (Fig. 53-11A). The appearance of GnRH pulsatility early in puberty is associated with decreased sensitivity of the hypothalamic-pituitary system to circulating sex steroids. The low GnRH and gonadotropin secretion during the prepubertal years appears to be due to high sensitivity of the hypothalamic-pituitary system to negative-feedback inhibition by gonadal steroids (see Fig. 53-11B). Before puberty, even low levels of sex steroids are sufficient to feed back on the hypothalamic-pituitary system and block the release of gonadotropins. After puberty, the levels of steroids required to block gonadotropin release progressively increase. Thus, the sensitivity of the hypothalamic-pituitary system to inhibition by sex steroids falls at puberty to reach the low level that is characteristic of the adult (see Fig. 53-11C). The precipitating event that is responsible for initiating pulsatile GnRH release is unknown, although it may reflect the maturation of hypothalamic neurons. Once a pulsatile pattern of gonadotropin secretion is established, it continues throughout reproductive life.


FIGURE 53-11 Gonadotropin function during life. A, Levels of both LH and FSH peak during fetal life and again during early infancy, before falling to low levels throughout the rest of childhood. At the onset of puberty, LH and FSH levels slowly rise and—in females—begin to oscillate at regular monthly intervals. At menopause, gonadotropin levels rise to very high levels. The four insets show daily changes. B, In childhood, even very low sex steroid levels are sufficient to fully suppress gonadotropin output. In adolescence, higher levels—and, in adults, even higher levels—of sex steroids are required to suppress gonadotropin release. C, This graph is a plot of age versus the midpoints of curves such as those in B.

Multiple factors control the timing of puberty

In girls, adrenarche leading to pubarche occurs between 8 and 13 years of age, and gonadarche leading to menarche and thelarche occurs between 12 and 13 years of age. The earliest physical manifestation of puberty in boys is an increase in testicular volume, which usually occurs between 9 and 14 years of age (Table 53-1).

TABLE 53-1

Tanner Stages in Male and Female Puberty






Preadolescent. No pubic hair is present, only vellus hair, as on the abdomen.

Preadolescent. The penis, scrotum, and testes are the same size—relative to body size—as in a young child.

Preadolescent. Breasts: only papillae are elevated.


Pubic hair is sparse, mainly at the base of the penis (boys) or along labia majora (girls).

Scrotum and testes are enlarged.

Breast buds begin to develop. Breasts and papillae are both elevated, and the diameter of the areolae increases.


Pubic hair is darker, coarser, and curlier and spreads above the pubis.

Penis is enlarged, predominantly in length. Scrotum and testes are further enlarged.

Breasts and areolae further enlarge.
Vagina enlarges and begins producing a discharge.
Menstrual periods may begin.


Pubic hair is of the adult type, but covers an area smaller than in most adults.

Penis is further enlarged in length and also in diameter. Scrotum and testes are further enlarged.

Areolae and papillae project out beyond the level of the expanding breast tissue.
Menstruation and ovulation begin. Periods will most likely be irregular.


Adult pattern.

Adult pattern.

With further enlargement of the breast, the areolae are now on the same level as the rest of the breast. Only the papillae project. Adult pattern.

*The official Tanner stages for females include pubic hair and breast development.

The precise cause of the onset of puberty is not completely understood. Multiple intrinsic (genetic) and extrinsic (environmental) factors play a role. Genetic factors appear to be major determinants of pubertal onset. Other factors, such as nutrition, geographic location, and exposure to light, also play a role. Over the last century, the age of girls at menarche in the United States and Europe has gradually decreased. The reason that menarche now occurs at a younger age is incompletely understood. It could be due to improved nutrition. However, better nutritional status alone cannot completely explain the decreased age of pubertal onset. Proximity to the equator and lower altitudes are also associated with early onset of puberty. A loose correlation is also seen between the onset of menarche in the mother and the onset of menarche in the daughter. The onset of puberty is also related to body composition and to fat deposition. Severe obesity and heavy exercise delay puberty.

Androgens and estrogens influence secondary sex characteristics at puberty

Profound alterations in steroid hormone secretion during the peripubertal period cause changes in the primary sex organs and secondary sex characteristics. In both sexes, the process of puberty can be divided into five developmental stages—referred to as the Tanner stages—based on the extent of pubic hair growth and genital and breast development. In males and females, Tanner stage 1 is the prepubertal state and Tanner stage 5 is the adult state (Fig. 53-12 and Table 53-1).


FIGURE 53-12 Tanner stages of puberty based on pubic hair, genital, and breast development in boys and girls. Pubic hair and genital/breast development may not be synchronous and are usually scored separately. For example, a girl may be at breast stage 3 but pubic hair stage 2. (Data from Carel JC, Léger J: Clinical practice. Precocious puberty. N Engl J Med 358:2366, 2008.)


The range of onset of normal male puberty extends from 9 to 14 years. Boys complete pubertal development within 2 to image years. In a normal male, the first sign of puberty (Tanner stage 2) is enlargement of the testes to >2.5 cm (see Fig. 53-12B). Testicular enlargement is mainly due to growth of the seminiferous tubules with some contribution by Leydig cell growth. imageN53-3 In normal boys, pubic hair generally develops 1 to image years after genital development. Pubic hair growth can be due to adrenarche or gonadarche and therefore can occur independently of genital growth.


Testicular Size

Contributed by Ervin Jones

Testicular size is generally determined using a ruler or calipers. It is expected that a length of >2.5 cm is compatible with the onset of normal pubertal development. The testicular volume index is defined as the sum of the product of length × width for the left and right testes. An orchidometer allows direct comparison of the patient's testes with an ovoid of measured volume. A popular method uses the Prader orchidometer, a set of solid or hollow ovoids encompassing the range of sizes from infancy to adulthood (1 to 25 mL). The volumes of the testes are then recorded; a volume of 3 mL closely correlates with the onset of pubertal development.

The male sex steroids, which are known as androgens, affect nearly every tissue in the body, including the brain. The changes that occur in male puberty are induced mainly by testosterone secreted by the testes. Testosterone stimulates adult maturation of the external genitalia and accessory sex organs, including the penis, the scrotum, the prostate, and the seminal vesicles. It also induces the male secondary sexual characteristics, which include deepening of the voice, as well as evolving male patterns of hair growth. imageN53-4 Testosterone also has anabolic effects, including stimulation of linear body growth, nitrogen retention, and muscular development in the adolescent and mature male. The biological effects of testosterone and its metabolites can be classified according to their tissue sites of action. Effects that relate to growth of the male reproductive tract or development of secondary sexual characteristics are referred to as androgenic, whereas the growth-promoting effects on somatic tissue are called anabolic.


Male Secondary Sex Characteristics

Voice and Hair Patterns

Contributed by Ervin Jones

Androgens also determine the male secondary sexual characteristics, which include deepening of the voice as well as evolving male patterns of hair growth. The changes in the voice are a result of androgen-dependent effects on the size of the larynx as well as the length and thickness of the vocal cords. In boys, the length of the vocal cords increases by ~50% during puberty, whereas girls have little increase in vocal cord length. The surfaces of the human body that bear secondary sexual hair include the face (particularly the upper lip, chin, and the sideburn areas), the axilla, and the pubic region. Temporal hair recession and male-pattern balding—beginning above the temples (i.e., receding hairline) and at the vertex of the scalp—are also androgen-dependent phenomena.

The pubertal growth spurt, a marked increase in growth rate (total body size), occurs late in puberty in boys. The acceleration of growth appears due to the combined effects of increased secretion of growth hormone and testosterone. In boys, height increases by an average of 28 cm during the pubertal spurt. The 10-cm mean difference in adult stature between men and women is due to a greater pubertal growth spurt in boys and to greater height at the onset of peak pubertal height velocity in boys compared with girls. Before puberty, boys and girls have the same mean body mass, skeletal mass, and body fat. However, men have 150% of the average woman's lean and skeletal body mass, and women have 200% of the body fat of men. Men have twice the number of muscle cells of women, and 1.5 times the muscle mass.


The first physical sign of puberty in girls is usually the onset of thelarche that begins between 10 and 11 years of age (see Fig. 53-12A). During the next 3 to 5 years, the breasts continue to develop under the influence of several hormones. Progesterone is primarily responsible for development of the alveoli (see Fig. 56-11C). Estrogen is the primary stimulus for development of the duct system that connects the alveoli to the exterior. Insulin, growth hormone, glucocorticoids, and thyroxin contribute to breast development, but they are incapable of causing breast growth by themselves.

During puberty, the uterus and cervix enlarge, and their secretory functions increase under the influence of estrogens (mainly estradiol). The uterine glands increase in number and length, and the endometrium and stroma proliferate in response to estrogens. The mucous membranes of the female urogenital tract respond to hormones, particularly estrogens.

Menarche usually occurs around 2 years after the initiation of thelarche. In the United States, most girls experience menarche between the ages of 11 and 13 years, the average age is 12.5 years, and the normal range is between 8 and 16 years. During puberty, a girl's body shape changes in response to rising levels of estradiol. The hips and pelvis widen and the proportion of body fat increases (compared with males) and distributes mainly to the breasts, hips, buttocks, thighs, upper arms, and pubis to produce the typical adult female body shape.

The appearance of secondary sex characteristics at puberty completes sexual differentiation and development

Although at birth humans have the primary and secondary sex organs necessary for procreation, final sexual maturity occurs only at puberty. Profound alterations in hormone secretion during the peripubertal period cause changes in the primary and secondary sex organs. In the following chapters the events occurring in puberty are discussed in more detail for both males (see Chapter 54) and females (see Chapter 55).