Review of Medical Physiology - William F. Ganong 2002

Endocrine System, Metabolism, and Reproduction
Sex Differentiation and Development
Sex Differentiation and Development - Precocious and Delayed Puberty

Precocious Puberty

The main causes of human precocious puberty are listed in Table 23-2. Early Development of secondary sexual characteristics in the absence of gametogenesis is caused by the pathological action of androgens in immature males and estrogens in immature females. This syndrome is termed pseudoprecocious puberty to distinguish it from true precocious puberty, which is caused by the early, yet normal, pubertal pattern of pituitary gonadotropin secretion (Fig. 23-12). Numerous cases have been described in which the onset of precocious puberty was an endocrine symptom of hypothalamic disease (See Chapter 14). Interestingly, in some experimental animals and humans, lesions of the ventral Hypothalamus near the posterior pituitary cause precocious puberty. The lesion may result from the disruption of Neural Pathways, inhibition of the GnRH pulse generator, or chronic irritation of the GnRH secretory zone through the creation of a focus around the lesion. Pineal tumors are sometimes associated with precocious puberty, but evidence indicates that this occurs only in the event of secondary hypothalamic damage. Precocious maturation caused by these or other hypothalamic lesions occurs with equal frequency in both sexes, although its constitutional form is more common in girls. In addition, premature gametogenesis and steroidogenesis can occur without the pubertal pattern of gonadotropin secretion (gonadotropin-independent precocious puberty). In this condition, at least in some cases, the sensitivity of LH receptors to gonadotropins is increased due to an activating mutation in the G protein coupled to adenylate cyclase-linked receptors.

Class="center">Table 23-2. Classification of causes of human precocious puberty

Delayed puberty or its absence

The normal age range for the onset of adolescent changes is so wide that puberty is not considered pathologically delayed until the age of 17 for menarche or 20 for testicular development. Delayed maturation due to panhypopituitarism is associated with dwarfism and other endocrine disorders. Patients with a 40,X (XO) chromosome Complement and gonadal dysgenesis are also short in stature. In some individuals, puberty is delayed even in the presence of Gonads and the preservation of other endocrine Functions. In males, these clinical abnormalities are termed eunuchoidism; in females, primary Amenorrhea (see below).

Menopause

With advancing age, the Ovaries of women become insensitive to gonadotropin stimulation, their function declines, and ovarian cycles eventually cease (menopause). This insensitivity is associated with, and probably caused by, a depletion in the pool of primordial follicles, which are exhausted by the time of menopause (Fig. 23-13). The ovaries no longer secrete progesterone and 17$eta$-estradiol in adequate amounts; small quantities of estrogens are produced solely through the aromatization of circulating androstenedione (See Chapter 29). The Uterus and Vagina undergo gradual atrophy. Due to negative feedback resulting from decreased estrogen and progesterone levels, the secretion of FSH and LH increases, and their plasma concentrations reach high levels. Older female mice and rats exhibit a prolonged period of diestrus (from Greek dia, between, and oistros, vehement desire, the time between periods of sexual desire in female mammals) and elevated gonadotropin levels, but a distinct menopause has not yet been described in these animals.

Fig. 23-12. Constitutional precocious puberty in a 3-year-old girl. The patient developed pubic Hair and began menstruating at the age of 17 months (Reproduced with permission from Jolly H: Sexual Precocity. Thomas, 1955).

In women, menstruation typically becomes irregular and ceases between the ages of 45 and 55. Since the early 20th century, the average age of menopause has increased and now stands at 52 years. Following the cessation of ovarian function, women frequently experience sensations of warmth spreading from the trunk to the face (hot flashes), night sweats, and a variety of other somatic symptoms. Hot flashes occur in 75% of menopausal women and may persist intermittently for up to 40 years. They are also documented in cases of premature menopause induced by bilateral oophorectomy. This symptom is treated with estrogens. Furthermore, hot flashes occur in men following castration; the underlying mechanism remains unknown, although they coincide with episodic bursts of LH secretion occurring at intervals of 30 to 60 minutes or longer (pulsatile secretion). In the absence of gonadal Hormones, the frequency of these episodes decreases. Each hot flash begins with the onset of secretory discharge. However, LH itself is not responsible for the symptoms, as they can persist following hypophysectomy. It appears that a specific estrogen-sensitive factor in the hypothalamus triggers both LH release and the onset of the hot flash.

Although testicular function declines slowly with age, scientific evidence indicates that there is no male equivalent to the female menopause (Climacteric).

Fig. 23-13. Number of primordial follicles in the ovaries of women of various ages. Open squares represent premenopausal women (regular menses); filled squares, perimenopausal women (irregular menses for at least a year); filled triangles, postmenopausal women (no menses for at least a year). Note that the vertical scale is logarithmic and values are given for one Ovary, not both (Reproduced with permission from Richardson SJ, Senikas V, Nelson JF: Follicular depletion during the menopausal transition: Evidence for accelerated loss and ultimate exhaustion. J Clin Endocrinol Metab 1987;65:1231).