Precocious Puberty
Navine G. Haworth
When reflecting back to one’s own era of transition into adolescence, some may say it was a very confusing period, with much angst with the rapid changes of physical, emotional, and psychosocial development. Some may remember it as a period of celebration and anticipation, from a child toward becoming an adult. What do we anticipate will be the feelings of our children and the future generations, with the timing of adolescence being pushed further into the period of childhood? Should we expect to see an early elementary school child undergo this period of transition, rather than the later elementary school child or the child in junior high? As more and more children shift toward this trend, will that become the new “norm”? With the trends emerging within adolescent medicine, this is indeed suggested to become the norm.
With this emerging trend, it is only appropriate that chiropractors should become familiar with the area of adolescence and early-onset puberty if they are likely to see a pediatric patient population. We should be familiar with what is considered within normal age range for puberty that is supported by the literature. We should be familiar with guidelines and recommendations for investigating and evaluating the child. Some specialists in the area of adolescent medicine are concerned that we may be subjecting children to extensive investigation, when simply a new goal post has been set for the onset of adolescence. However, if we should change the goal post to an earlier age of onset, is it then possible that we may potentially miss those children with an underlying pathology in which precocious puberty is its expression.
In the area of adolescent medicine, a topic of much controversy and differing views is that of what is considered normal age for onset of puberty. Look at the elementary and junior high school grounds, popular teen icons, and your practice setting; it is astounding as to how our youth seem to be developing compared with one to two decades earlier. What we used to consider children, we are now labelling “tweens,” and the definition of a “tween” is equally confusing. Ages range from 8 to 12 years (1) and 10 to 12 years (2), when you are not quite a teen, and not quite a child; the inbetween stage of childhood and adolescence (1).The pressure of our media encouraging our children to look more like adults and engage in more adult-type behaviors. Aside from just observation, there is scientific documentation of children growing and developing at an earlier stage than in previous decades. Steingraber (3), in her literature review of early onset of puberty in the United States, states that girls get their first period, on average, a few months earlier than girls 40 years ago, but their breasts begin to develop 1 or 2 years earlier. The childhoods of US girls have been significantly shortened. Questions remain as to whether this is a normal variation occurring as we have better health and nutrition (4) or whether many more factors are contributing to this trend.
The following further explores the definition and classification of precocious puberty, some of the proposed causes, and long-term effects of earlier onset puberty. The majority of the focus is on female precocious puberty, as it appears to be the most researched due to predominance and increasing incidence.
Considering this, where to draw the line is more challenging as to when is normal pubertal onset and when is onset “too early,” or “precocious.”
DEFINITION AND CRITERIA
Precocious puberty is often caused by early activation of the gonadotropic axis with pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH), leading to an increase in luteinizing hormone and, to a lesser degree, secretion of follicle-stimulating hormone. This is effectively what occurs with central precocious puberty (CPP). Other forms of precocious puberty can
be caused by autonomous production of sex steroids by the gonads or adrenals; pharmacologic or environmental exposure to sex steroids; or production of human chorionic gonadotropin by tumors.
be caused by autonomous production of sex steroids by the gonads or adrenals; pharmacologic or environmental exposure to sex steroids; or production of human chorionic gonadotropin by tumors.
Whilst there is an established definition and classification for precocious puberty, several researchers and pediatricians have encouraged a review of the accepted definition. The need for review is because of the variation emerging as to pubertal onset and if we are considering these children as having a potential pathology and having them undergo extensive testing because of these emerging changes. Many suggest that, because of our improved nutrition and health care, it is likely we will have variations of pubertal development emerging, just as our life span has increased as a result of these changes. Styne (5) suggests that the secular trend toward an earlier age of puberty implicates health and nutrition as major determinants of the onset of sexual maturation. Girls in the United States are maturing at an earlier age than they did 30 years ago, and the number of them who are diagnosed with precocious puberty is on the rise (6).
The normal age range for puberty in girls is 9 to 16 years of age, and 13 to 15 years of age in boys (7). Precocious puberty has most commonly been defined as the onset of puberty before the age of 8 years in girls and 9 years in boys. It involves not only early physical changes of puberty, but it can also effect growth and acceleration, in particular acceleration of bone maturation. Because of this, the epiphyseal plates have a tendency to close down prematurely, resulting in a shortened stature (8).
There exist several types of precocious puberty. These include the following:
CPP (also known as true precocious puberty): this type is gonadotropin-dependent and involves early maturation of the entire hypothalamic-pituitarygonadal axis; these children will have the full spectrum of physical and hormonal changes of puberty (9). A large majority (>90%) of CPP are idiopathic. When there is no evidence or cause of CPP seen on magnetic resonance imaging (MRI) or computed tomography (CT), it is considered “idiopathic” (10). Possible nonidiopathic causes are central nervous system (CNS) dysfunctions such as congenital, destructive tumors; excessive pressure hydrocephalus; previous or current infection/inflammation; injury; irradiation; and GnRH-secreting hypothalamic hamartoma (11). The exact pathogenesis is not clear; however, it is speculated that local pressure, abnormal neuronal connections, independent endocrine activity, or a combination of these factors may play a role in CNS abnormalities causing CPP (12).
Pseudoprecocious or peripheral precocious puberty: this is much less common and refers to conditions in which increased production of sex steroids is gonadotropin-independent (9). Some causes include exogenous sex steroids or gonadotrophins, chronic primary hypothyroidism, ovarian tumors, benign ovarian cysts, feminizing adrenal tumors, virilizing adrenal tumors, and McCune Albright syndrome (12).
Most girls (95%) have idiopathic true precocious puberty. Boys (>50%) are likely to have an underlying pathology resulting in precocious puberty (8). Statistics indicate that precocious puberty currently affects 1 in 5,000 children and is 10 times more common in girls (6).
As previously mentioned, new definitions have emerged in adolescent medicine as to when precocious puberty is really to be considered precocious. This has been, in part, because of one very instrumental study in 1997:the Pediatric Research in Office Settings study (13). This study consisted of 17,077 girls and investigated the normal onset of puberty; it was performed across pediatric clinics. These girls were aged 3 to 12 years of age. What they observed from this study was that pubertal onset tended to be earlier than expected. From the study population, the mean age of breast development in African American girls was 8.87 ± 1.93 years and in white girls 9.96 ± 1.82 year. This led to a different appreciation of the normal variation of age of pubertal onset. They concluded that girls who are seen in a sample of pediatric practices across the United States are developing pubertal characteristics at younger ages than currently used norms. Practitioners may need to revise their criteria for referral of girls with precocious puberty, with attention to racial differences. From this study, precocious puberty would be considered before 5 years of age in African American girls and before 6.3 years of age in white girls if you were to consider the 2 standard deviations (SDs) below the average.
Klein (8) further supports that pubertal onset norms need to be reconsidered. The age of normal pubertal development is based on 95% of the population, or 2 SDs below the mean age of pubertal onset in normal girls. Hence, 2.5% of normal girls have onset of puberty before age 8. Klein (8) asks the question of whether puberty is truly precocious when it occurs between the ages of 6 and 8 years, or is it simply the outer limits of normal. Kaplowitz and Oberfield (14) published the Lawson Wilkins Pediatric Endocrine Society guidelines recommending that puberty be considered precocious only when breast development or pubic hair appears before age 7 years in white girls and age 6 years in black girls. From these guidelines, they issued a statement in response to the Pediatric Research in Office Settings study that the current recommendation—that breast development before the age of 8 is precocious—is based on outdated studies. They also recommend lowering the normal age of puberty to 7 years in white girls
and 6 years in black girls. Many practitioners feel that these newer guidelines present a practical, evidence-based approach (15). However, others are of the opinion that if these guidelines are employed, it will lead to a significant under-diagnosis of endocrine conditions (16). Experts, particularly in the field of endocrinology, feel that to change these guidelines will simply result in many children who have pathological causes of early development to go undetected. Midyett et al. (16) believe that the new recommendations were based only on a single epidemiological study that focused on too small of a set of criteria for premature thelarche and adrenarche. It is believed that to use these recommendations will result in the underdiagnosis of endocrine pathologies. The researchers substantiate their argument through a study in an outpatient endocrinology clinic, where they looked at 1,570 patients over a 5-year period. The main groups were black girls aged 6 to 8 years and white girls aged 7 to 8 years. What they found was that a total of 105 of the 223 patients (47.1%) had signs consistent with true precocious puberty (i.e., two signs of puberty); overall, 12.3% of patients had other endocrine conditions that included congenital adrenal hyperplasia, McCune Albright Syndrome, growth hormone deficiency, hypothyroidism, hyperinsulinism, pituitary adenoma, and neurofibromatosis. In addition, a total of 35.2% of girls with true precocious puberty demonstrated bone ages more than 3 SDs above the mean. This often results in reduced growth potential. Hence, they suggest that girls who show signs of puberty at the age of 6 to 8 years should not be considered normal or benign and that potentially accepting new recommendations may only result in failure to identify more serious underlying conditions that may respond to interventions.
and 6 years in black girls. Many practitioners feel that these newer guidelines present a practical, evidence-based approach (15). However, others are of the opinion that if these guidelines are employed, it will lead to a significant under-diagnosis of endocrine conditions (16). Experts, particularly in the field of endocrinology, feel that to change these guidelines will simply result in many children who have pathological causes of early development to go undetected. Midyett et al. (16) believe that the new recommendations were based only on a single epidemiological study that focused on too small of a set of criteria for premature thelarche and adrenarche. It is believed that to use these recommendations will result in the underdiagnosis of endocrine pathologies. The researchers substantiate their argument through a study in an outpatient endocrinology clinic, where they looked at 1,570 patients over a 5-year period. The main groups were black girls aged 6 to 8 years and white girls aged 7 to 8 years. What they found was that a total of 105 of the 223 patients (47.1%) had signs consistent with true precocious puberty (i.e., two signs of puberty); overall, 12.3% of patients had other endocrine conditions that included congenital adrenal hyperplasia, McCune Albright Syndrome, growth hormone deficiency, hypothyroidism, hyperinsulinism, pituitary adenoma, and neurofibromatosis. In addition, a total of 35.2% of girls with true precocious puberty demonstrated bone ages more than 3 SDs above the mean. This often results in reduced growth potential. Hence, they suggest that girls who show signs of puberty at the age of 6 to 8 years should not be considered normal or benign and that potentially accepting new recommendations may only result in failure to identify more serious underlying conditions that may respond to interventions.
Of further interest are the racial differences existing in the United States between white and black girls and pubertal onset that has been discovered from these studies. Current recommendations change the age limit for precocious breast and pubic hair growth to age 6 years for black girls and age 7 years for white girls. However, no current evidence shows that black boys mature earlier than white boys; thus, incidence of precocious puberty among boys is similar between both races (9).
The usual sequence of pubertal events in boys include an increase in penis and testicle size; appearance of straight pubic hair; minor voice changes; first ejaculation (spermarche); appearance of kinky pubic hair; onset of maximum growth; growth of hair in armpits; more detectable voice changes; and growth of facial hair. In girls, puberty commences with either breast enlargement or pubic hair development. Axillary hair is next, and whilst these changes occur, girls obtain height and their hips begin to widen. Menarche occurs late in puberty. Normal range for menarche is 9 to 15 years of age (17). Refer to Tanner staging to reference normal characteristics of development.
It has been observed in the United States that the age of thelarche is also falling more rapidly than the age of menarche. Girls tend to get their breasts, on average, 1 to 2 years earlier than did girls 40 years ago. The mean age of thelarche is about 10 years for white girls and 9 years for black girls (3).
In addition to the onset of puberty occurring earlier in girls, the age of menarche also seems to be decreasing and occurring at a younger age. One study has revealed that from 1973 to 1994 the age of menarche decreased by 9.5 months among black girls and 2 months among white girls. From this study, the authors suggest a combination of genetic as well as environmental and racial factors have produced such variation (17). Anderson et al. (18) investigated whether menarche occurred earlier in the 1990s compared with 25 years earlier. They also assessed whether the occurrence of menarche in relation to weight status and race had changed over time. What they had concluded from their study is that the average age of menarche dropped by 2½ months (from age 12.75 to 12.54 years). This was also in congruence with a rise in body mass index (BMI) above the 85th percentile, from 16% to 27% among girls 10 to 15 years of age, over the 25 years between surveys. In addition, black girls had a lower average age of menarche than did white girls, independent of weight.
Menarche is not a reliable marker for pubertal onset because it is only loosely correlated with the timing of thelarche and pubarche. In addition, the correlation of the onset of puberty with the age of menarche seems to have decreased over the last few decades (3). Kaplowitz (19) suggests that the decoupling of puberty’s onset from menarche suggests environmental signals may be influencing thelarche and menarche in different ways.
Tables 22.1 and 22.2 list the different studies that have characterized the ages of pubertal onset for boys and girls.
CAUSES OF PRECOCIOUS PUBERTY
There are numerous theories as to the causes of the increasing incidence of precocious puberty. Though some causes seem quite plausible, such as increasing use of endocrine-disrupting chemicals in the environment, other causes seem intriguing with regard to the psychological and social aspects that can be contributing to early pubertal onset.
Environmental Influences
Though some have argued that environmental exposures are too transient to cause any such long-term
effects as early pubertal onset (20), many researchers have found compounding evidence to suggest that short-term exposures can have convincing effects to cause precocious puberty.
effects as early pubertal onset (20), many researchers have found compounding evidence to suggest that short-term exposures can have convincing effects to cause precocious puberty.
TABLE 22.1 | |||||||||||||||||||||||||||||||||||||||||||||
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There is much information available in the literature regarding environmental causes such as the use of pesticides, contaminations, and hormones utilized for growth and maturation of livestock and the potential effect on pubertal onset. A study by Colón et al. (21) described in their investigation the use of phthalate esters being widely used in Puerto Rico, where there is also the highest incidence of early thelarche (breast development) ever reported. In this study, blood analysis was performed on 41 girls with premature thelarche, as well as 35 control subjects. Significantly higher levels of these phthalates were found in 68% of the experimental group. Only one elevated level was detected in the control group. They concluded that a possible association between plasticizers with known estrogenic and antiandrogenic activity and the cause of premature breast development in a human female population may exist.
In another study investigating environmental causes (22), this time in the form of pesticides, a retrospective study was performed on migrating children. In particular, the study looked into a link between children migrating from developing countries into Belgium who presented with precocious puberty. They were drawn to the hypothesis that these children may have had exposure to estrogenic endocrine disrupters in the form of pesticides. A toxicologic screening derived an organochlorine derivative of dichlorodiphenyltrichloroethane. They concluded that a relationship between transient exposure to endocrine disrupters and sexual precocity has been suggested.
In a more dramatic case (23), a known large-scale industrial accident occurred in Michigan in 1973, in which a fire retardant was accidentally mistaken for a nutrient and added to livestock feed. As a result, dairy and animal products were consumed and contaminated with polybrominated biphenyls (PBBs). It has been estimated that more than 4,000 people were exposed, and the PBB exposure is suspected to have caused endocrine disruption. Pubertal development of girls aged 5 to 24 years of age (n = 327) who were exposed to PBB in-utero and through breast milk were investigated. The study found that girls who were exposed to high levels of PBB in-utero (>7 parts per billion) had an earlier age of menarche (mean age, 11.6 years) compared with girls who were breast-fed and exposed to lower levels of PBB in-utero (mean age, 12.2 to 12.6 years) or girls who were not breast-fed (mean age, 12.7 years). In addition, perinatal exposure to PBBs was associated with earlier pubarche (pubic hair stage) in breast-fed girls. From this study they hypothesized that organohalogens during prenatal and postnatal exposure can potentially affect pubertal events.
A study from Italy (24) involving three pre-pubertal girls aged 17 months, 7 years, and 9 years of age presented with a somewhat transient precocious puberty. All three girls presented with enlarged breasts, areolar
and vaginal hyperpigmentation, as well as vaginal bleeding. All three girls also presented with Tanner stage 2 breast development with no pubic hair and no accelerated bone growth. These features were congruent with episodic estrogen intake. It was concluded that accidental estrogen intake had occurred from contaminated food because there had been no drug contamination or dermatologic preparation that caused contamination. The authors concluded that this seems particularly common in Italy because of widespread consumption of meat from very young animals that had been fed with estrogen to accelerate bone growth.
and vaginal hyperpigmentation, as well as vaginal bleeding. All three girls also presented with Tanner stage 2 breast development with no pubic hair and no accelerated bone growth. These features were congruent with episodic estrogen intake. It was concluded that accidental estrogen intake had occurred from contaminated food because there had been no drug contamination or dermatologic preparation that caused contamination. The authors concluded that this seems particularly common in Italy because of widespread consumption of meat from very young animals that had been fed with estrogen to accelerate bone growth.
TABLE 22.2 | ||||||||
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