Figure 29.6 Increases (± standard error) in circulating levels of gonadotropins and adrenal and gonadal steroids through puberty in girls. DHEA, dehydroepiandrosterone; DHEAS, dehydroepiandrosterone sulfate. (From Emans SJH, Goldstein DP. The physiology of puberty. In: Emans SJH, Goldstein DP, eds. Pediatric and adolescent gynecology. 3rd ed. Boston, MA: Little, Brown, 1990:95, with permission.) act as an endogenous pulse generator. At puberty, the GnRH pulse generator is reactivated (i.e., disinhibited), leading to increased amplitude and frequency of GnRH pulses. In turn, the increased GnRH secretion results in increased gonadotropin and then gonadal steroid secretion. What causes this “disinhibition” of GnRH release is unknown.
The relationship between body mass and the onset of puberty focused attention on leptin, produced by adipocytes, as a candidate for the factor initiating puberty. In the infertile leptin-deficient mouse, leptin therapy can induce sexual maturation and maintain fertility. Observations of two patients with leptin receptor mutations who failed to enter puberty suggest that leptin may have a similar role in humans (25).
Longitudinal studies of leptin secretion noted that there is increased leptin secretion around the time of pubertal onset. Leptin levels are increased throughout puberty in girls but not in boys. There is speculation that leptin is a trigger for pubertal onset, but a more widely held view is that leptin plays a more permissive role in regulating pubertal onset (25).
Aberrations of Pubertal Development
Classification Several aberrations of pubertal development, as detailed in Table 29.1, can occur in girls. Pubertal aberrations can be classified in four broad categories: 1. Delayed or interrupted puberty exists in girls who fail to develop any secondary sex characteristics by age 13, have not had menarche by age 15 (95th percentile is 14.5 yr), or have not attained menarche 5 or more years since the onset of pubertal development.
Table 29.1 Aberrations of Pubertal Development
I. Delayed or interrupted puberty
A. Anatomic abnormalities of the genital outﬂow tract 1.
2.
a.
b.
B.
1.
Gonadal dysgenesis with stigmata of Turner syndrome 2.
a. 46,XX b. 46,XY 3. Early gonadal “failure” with apparent normal ovarian development
C. Hypogonadotropic (luteinizing hormone and follicle-stimulating hormone <10 mIU/mL) hypogonadism 1.
2.
a.
Associated with midline defects (Kallmann syndrome) b.
Independent of associated disorders c.
d.
e.
Table 29.1 Continued 3.
Associated with multiple hormone deficiencies 4.
Neoplasms of the hypothalamic–pituitary area a.
b.
c.
5.
6.
After irradiation of the central nervous system 7.
Severe chronic illnesses with malnutrition 8.
9.
10.
Antidopaminergic and gonadotropin-releasing hormone–inhibiting drugs (especially psychotropic agents, opiates) 11.
12.
13.
Use of chemotherapeutic (especially alkylating) agents
II.
A.
B.
III.
A.
1.
2.
3.
4.
5.
6.
7.