Mini Review

HOR MON E Horm Res Paediatr 2012;77:137–145 Received: September 2, 2011

RE SE ARCH I N DOI: 10.1159/000336325 Accepted: January 6, 2012
Published online: April 12, 2012
PÆDIATRIC S

Recent Secular Trends in Pubertal Timing:

Implications for Evaluation and Diagnosis
of Precocious Puberty
Kaspar Sørensen Annette Mouritsen Lise Aksglaede Casper P. Hagen
Signe Sloth Mogensen Anders Juul
Department of Growth and Reproduction, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen,
Copenhagen, Denmark

Key Words translated into revision of age limits for evaluation of PP due
Precocious puberty ⴢ Pubertal timing ⴢ Pubertal to the risk of misdiagnosing rapid progressive PP as well as
examination ⴢ Orchidometry ⴢ Thelarche intracranial and other underlying pathology.
Copyright © 2012 S. Karger AG, Basel

Abstract
The decline in age at puberty in the general population has Introduction
been paralleled by an increase in the number of girls referred
for evaluation of precocious puberty (PP). In 1999, The Law- Puberty is an important developmental milestone. It
son Wilkins Pediatric Endocrine Society recommended a can be considered as a complex sequence of biological
lowering of the age limit for evaluation of PP in girls. How- events leading to progressive maturation of sexual char-
ever, the limited evidence on which these recommendations acteristics ultimately leading to attainment of full repro-
were based led many experts to question these new sugges- ductive capacity. The timing of puberty has received con-
tions. The emergence of new European pubertal timing data siderable attention during the past decades due to the as-
evaluated by robust clinical as well as biochemical markers sociations with risk of breast cancer and cardiovascular
has broadened our insight on how to interpret the recent disease in adulthood [1].
pubertal changes. The recent pubertal trends have resulted Until the mid-20th century, a gradual decline in age at
in a concomitant lowering of the lower limit of normality of menarche has been reported in most industrialized pop-
the pubertal onset. However, evidence suggests that age at ulations [2]. Thereafter, this trend ceased as a result
the gonadotropin and sex steroid surges have not changed. of increased stability in socioeconomic conditions, im-
Thus, it looks as if an increasing proportion of contemporary proved nutrition and hygiene. In the 1990s, two Ameri-
early pubertal girls may experience isolated gonadotropin- can studies turned our attention towards new secular pu-
independent thelarche rather than central PP, which may not bertal trend in both girls and boys [3–7]. Although data
be discernible on pubertal examination alone. Thus, the from European populations collected in the same period
population-based limits of normality should not be directly failed to show similar trends [8, 9], contemporary studies

© 2012 S. Karger AG, Basel Kaspar Sorensen, MD

1663–2818/12/0773–0137$38.00/0 Department of Growth and Reproduction, GR-5064
Fax +41 61 306 12 34 Copenhagen University Hospital, Blegdamsvej 9
E-Mail [email protected] Accessible online at: DK–2100 Copenhagen (Denmark)
www.karger.com www.karger.com/hrp E-Mail kaspar.Soerensen @ rh.regionh.dk
now suggest similar drastic changes in European girls interplay between metabolic, nutritional, and steroidal
[10, 11] and to lesser extent in European boys [9, 12]. In factors [26].
addition, a parallel increase in the number of girls re- In girls, it is generally accepted that the appearance of
ferred for evaluation of precocious puberty (PP) has re- glandular breast tissue (thelarche) is the most reliable ini-
cently been reported [13]. tial sign of estrogenic activity, whereas appearance of pu-
The repeated American findings supporting an ongo- bic hair is attributable to a hormonally distinct process,
ing secular trend towards earlier pubertal timing elicited onset of adrenal gland androgen production (adrenarche),
a lively debate among pediatric endocrinologist concern- which is not directly related to ovarian activation [31].
ing the possible implication for the evaluation and diag- Visual grading of breast stages is generally uncomplicat-
nosis of PP, and prompted The Lawson Wilkins Pediatric ed in non-obese girls. However, discrimination of actual
Endocrine Society (LWPES) to recommend a lowering of glandular breast tissue from adipose tissue is extremely
the age limit for evaluation of PP in girls [14]. However, difficult in overweight and obese girls due to accumula-
the limited evidence on which these recommendations tion of excessive subcutaneous fat mimicking true glan-
were based as well as concerns of overlooking treatable dular breast development. Thus, in light of the obesity
pathological conditions underlying the precocious onset epidemic, the inherent risk of overclassification of prepu-
of puberty have led many experts to question these rec- bertal girls as being early pubertal needs to be considered.
ommendations [15–18]. However, the emergence of new The addition of breast palpation may partly overcome
European pubertal timing data evaluated by robust clin- this problem, and is therefore recommended in clinical
ical as well as biochemical markers has broadened our settings, as well as in clinical research studies.
insight of how to interpret the recent pubertal changes In boys, a testicular volume of more than 3 ml is gen-
[10, 12]. erally considered to be the most reliable marker of puber-
Genetic factors play a major role in the timing of pu- tal onset [32]. Testicular size is most accurately estimated
berty [19, 20]. However, the rapid advancement in puber- by ultrasonography, but a reliable proxy can be obtained
tal timing over the past decades clearly indicates an envi- by comparing the testicular size with the size-standard-
ronmental etiology. The obesity epidemic has received ized beans of a Prader orchidometer [33]. Due to the re-
special attention [21, 22]. Although consistent evidence quirement of testicular palpation, orchidometry has sel-
supports that higher adiposity is associated with earlier dom been performed in population-based studies, and
pubertal maturation in girls [23, 24], a similar relation- most of the current data, therefore, rely solely on visual
ship in boys remains controversial [12, 24, 25]. In addi- grading of genital development. However, the subtle
tion, changes in fetal nutrition, childhood dietary habits, changes in penile size and scrotal skin texture that be-
physical activity and exposure to endocrine disrupting come evident with the onset of puberty may be difficult
chemicals are other possible candidates that may influ- to appreciate, and the interobserver variation is accord-
ence the endogenous endocrine milieu, and therefore po- ingly substantially higher with genital staging than with
tentially affect maturation of the reproductive system orchidometry [34].
[26].
The present mini-review will focus on (1) secular
trends in pubertal timing evaluated by clinical and bio- Secular Trends in Pubertal Markers in Girls
chemical markers, and (2) implications for the evaluation
and proper diagnosis of PP. The timing of normal puberty has changed remark-
ably over the past centuries. Historical data from Europe
have shown a drastic decline in age at menarche from ap-
Basic Physiology of Puberty proximately 17 years in the early 19th century to approx-
imately 13 years by the mid-20th century (fig.  1) [35].
The activation of the hypothalamic-pituitary-gonadal Comparable downward trends have been reported from
(HPG) axis is the fundamental primary event for initia- the US during the first half of the 20th century [36]. From
tion of puberty. The HPG axis is transiently activated in the 1960s, the trend in age at menarche seems to have lev-
early infancy [27–29] followed by a relative, but not abso- eled off in both Europe and the US [3, 8, 9, 37], although
lute, quiescent period in childhood [30]. The factors re- minor, but statistically significant, decrements of 2.5–4
sponsible for the reactivation of the HPG axis at onset of months have been reported during the past 25 years [10,
puberty are still largely unknown, but involve a complex 11, 38].

138 Horm Res Paediatr 2012;77:137–145 Sørensen/Mouritsen/Aksglaede/Hagen/

Mogensen/Juul
 18 14.0

Age at menarche
Denmark
13.5

(years)
17 Portugal
13.0

Age at menarche (years)

Norway
16 12.5
US
1970 1980 1990 2000 Germany
15 Year of study
Finland
14 Spain
Greece
13
Netherlands
Fig. 1. Secular trend in age at menarche ac-
Belgium
cording to the first year of data collection. 12
Inset shows the past 50 years in which the 1830 1850 1870 1890 1910 1930 1950 1970 1990 2010 Poland
secular trend in age at menarche seems to Year of study
have ceased.

11.5 US 12.5

Age at TV >3 ml (years)

Denmark
Age at B2 (years)

11.0 Netherlands 12.0

Switzerland
10.5 Turkey 11.5
Italy
10.0 Sweden 11.0
Greece
9.5 Iceland 10.5
Fig. 2. Secular changes in age at onset of
breast stage 2 (B2; a) and of testicular vol- 1940 1960 1980 2000 2020 1940 1960 1980 2000 2020
ume of more than 3 ml (TV 13 ml; b) dur- a Year of study b Year of study
ing the last 60 years.

In contrast to menarche, age at onset of breast develop- years, 6.7% of white girls and 27.2% of African-American
ment seems to have declined markedly during the last girls in the PROS study [3] fulfilled the criteria for evalu-
two decades (fig. 2). Before the 1980s, the mean age at on- ation of PP with either breast or pubic hair development.
set of breast development was consistently reported to be These findings prompted The Lawson Wilkins Pediatric
approximately 11 years in both American and European Endocrine Society (LWPES) to re-examine the age limit
studies [32]. However, data from the American popula- for evaluation of PP in the US and recommended that
tion-based Third National Health and Nutrition Exami- evaluation should only be undertaken if clinical signs of
nation Survey (NHANES III) conducted from 1988 to puberty were present before the age of 7 years in white
1994 showed mean ages at onset of puberty in girls well girls and before the age of 6 years in African-American
below 10 years [6]. Although most marked changes were girls [14]. Many pediatric endocrinologists have subse-
observed in non-Hispanic black girls, low ages at onset of quently questioned the evidence on which these recom-
breast development were reported in all ethnic groups. mendations were based and argued that the PROS study
However, data reliability in the NHANES III was criti- was not representative for the general American popula-
cized due to reliance on visual grading of breast stages tion [17, 18]. In addition, it only included girls up to the
alone. Nevertheless, a contemporary large-scale Ameri- age of 12 years, and may therefore have missed the late
can study, the Pediatric Research in Office Settings pubertal girls potentially leading to a slight underestima-
(PROS) study, included breast palpation in 39% of the ex- tion of the true age at pubertal onset. However, based on
aminations and confirmed the NHANES III findings the newest US data by Biro et al. [39], the proportion of
with even marginally lower mean ages at onset of breast white and black girls presenting with breast development
development [3]. Using the classical diagnostic limit of 8 before the age of 8 years seems to be increasing further

Recent Secular Trends in Pubertal Horm Res Paediatr 2012;77:137–145 139

Timing
 recently been reported from other European countries
1.0 [40, 41]. This may indicate that the secular trends towards
0.8 earlier pubertal onset evident in the US during the 1990s
Probability of B2

0.6
may now be evident in Europe with a 15 years’ delay. At
present, the figures from Europe are not as drastic as
0.4
those seen in the US, although the most recent studies
2006–08
0.2
1991–93 indicate that approximately 5% of white girls have onset
0 of breast development before 8 years of age [11, 10, 40].
a 6 8 10 12 14 16 As for onset of later pubertal stages, a secular trend
1.0 analysis between HNANES III and the previous popula-
Probability of menarche

tion-based study, the Third National Health Examina-

0.8
tion Survey (NHES III), did not find evidence for ad-
0.6 vancement in age at onset of breast stage III–V in either
0.4 black or white American girls [7]. In contrast, age at onset
of breast stages III and IV had declined in parallel to the
0.2
decline in age at onset of breast development in The Co-
0 penhagen Puberty Study [10]. However, the evaluation of
b 10 12 14 16 18
these later stages of breast development may be subject to
1.0 considerable interobserver variation, and compatibility
Probability of TV >3 ml

0.8 between studies and time periods should therefore be in-

terpreted with caution. Nevertheless, data clearly suggest
0.6
a secular trend towards earlier onset of breast develop-
0.4 ment, whereas age at menarche has only changed margin-
0.2 2006–08 ally in both American and European girls. Although this
1991–93
may indicate that the pubertal period had lengthened
0
8 10 12 14 16 over the past decades, definite conclusion cannot be made
c Age (years) at present due to the cross-sectional nature of most pop-
ulation-based studies.
Fig. 3. Data on age at puberty in healthy girls and boys collected
in the Copenhagen area in two periods: 1991–1993 and 2006–
2008. Probability of attainment of breast stage B2 (or more) as- Secular Trends in Pubertal Markers in Boys
sessed by visual inspection and breast palpation (a), menarche by
the status quo (yes/no) method (b), and attainment of testicular Pubertal timing has not received the same attention
volume above 3 ml by use of Prader’s orchidometer (c) according in boys as in girls, and consequently fewer and mainly
to chronological age. Thin black lines represent the raw turn-bull
estimates. The 1991–1993 cohort is presented in green and blue smaller studies, many of which are not population-based,
and the 2006–2008 cohort in purple and orange in girls and boys, are available. Dating back to the earliest reports from the
respectively. Modified with permission [10, 12]. 1940s, age at onset of genital development has been con-
sistent around 11.5 years in both American and European
studies [32, 42]. In NHANES III, boys had a markedly
lower age at onset of genital development [4–6] than pre-
(10.4 and 23.4%, respectively), indicating that the secular viously reported from the US [7, 43–45]. However, due to
trends in onset of breast development may have contin- lack of data on pubertal onset from the previous popula-
ued since the NHANES III and PROS data were collected tion-based study (NHES III) [45], some controversies ex-
in the 1990s. ist on how to interpret the NHANES III findings [4, 5, 7,
In Europe, studies from 1990s did not support the 46]. The suggested extreme decline in age at male genital
American findings of earlier onset of breast development development was not supported by a similar secular trend
[8, 9]. However, more recently the Copenhagen Puberty in onset of pubic hair development. In addition, the lack
Study reported a 12-month decline in mean age at onset of strict interobserver policies in NHANES III has led
of breast development over a 15-year period in healthy many pediatric endocrinologist to speculate if the low age
Danish girls (fig. 3) [10]. Similar age at pubertal onset has at onset of genital development was a result of erroneous

140 Horm Res Paediatr 2012;77:137–145 Sørensen/Mouritsen/Aksglaede/Hagen/

Mogensen/Juul
classification of prepubertal boys as being in early puber- pants had blood samples available for the analyses of go-
ty [46, 47]. In support of the above-mentioned concerns, nadotropin and sex steroid levels [10, 12]. Surprisingly,
a contemporary American study using orchidometry the marked downward secular trend in age at breast de-
found that age at pubertal onset was compatible with pre- velopment was not paralleled by an earlier increase in go-
viously American and European studies [43]. Unfortu- nadotropin and estradiol levels in this study (fig. 4) [10].
nately, orchidometry was not performed in any of the US In contrast, lower estradiol levels were found in some of
population-based studies [32]. In Europe, few population- the pubertal age groups [10]. Although evaluation was
based studies are available, but in contrast to the contem- done solely by single non-stimulated gonadotropin and
porary American studies, some of these have performed estradiol levels with the risk of missing true pubertal
orchidometry in addition to genital staging for possible HPG axis activation during the early stages of puberty in
secular trend analysis (fig.  2) [8, 9, 48]. In general, no some girls [13], this potential bias would have affected
marked secular trend towards earlier age at pubertal onset both time periods equally in the Copenhagen Puberty
in boys was evident from the mid-1960s to the late 1990s Study. Thus, the lack of secular trends in gonadotropin
[8, 9], although slight indications have been reported [9]. and estradiol levels indicates that the recent advancement
However, The Copenhagen Puberty Study recently docu- in age at thelarche is not caused by earlier central gonad-
mented a decline of 3 months in age at onset of puberty otropin-dependent gonadal pubertal activation, but rath-
during a recent 15-year period [12] (fig. 3) evaluated by er suggests a gonadotropin-independent phenomenon
both genital staging and orchidometry. Thus, pubertal with possible increased estrogenic bioavailability or sen-
onset may be decreasing in boys, although to a much less- sitivity inducing isolated breast development. This may
er extent than seen in girls. In addition, the age limit of 9 also provide a plausible explanation for the lack of similar
years classically used to define precious puberty in boys marked secular changes in age at menarche [3, 10, 38], in
still seems to be valid from these population-based data. that attainment of menarche is dependent on a fully acti-
In accordance, the LWPES did not find evidence to sup- vated HPG axis, the timing of which does not seem to
port a lowering of the diagnostic age limit in boys [14]. have changed significantly during the last decades. How-
As for attainment of later pubertal stages, a secular ever, the exact gonadotropin-independent mechanisms
trend analysis between NHES III and NHANES III did involved in the isolated earlier thelarche are still un-
not find persuasive evidence in favor of the existence of known. Although the obesity epidemic is most likely in-
earlier age among boys entering genital stages 3–5, al- volved in the recent pubertal changes in girls [21, 50], ad-
though some indications were present in non-Hispanic vancement in age at puberty has been reported without
white boys [7]. In The Copenhagen Puberty Study, onset significant changes in BMI [10]. Thus, other environmen-
of later pubertal stages was attained at earlier ages just as tal factors that can modify sex steroid bioavailability and
yearly increment in testicular volume was greater now sensitivity such as changes in physical fitness [51] and nu-
compared with 15 years before [12]. However, as most trition as well as exposure to endocrine disruption chem-
studies on pubertal timing are conducted cross-section- icals [52] need to be considered.
ally, the possible changes in the progression of puberty In contrast to the findings in girls, the modest secular
should be interpreted with caution before they are con- trend towards earlier onset of puberty in boys was paral-
firmed by longitudinal studies. leled by a secular increase in age-adjusted LH levels in
The Copenhagen Puberty Study (fig. 4) [12]. In addition,
these changes seemed to be related to secular changes
Secular Trends in Reproductive Hormone Levels in BMI. Thus, the earlier timing of pubertal testicular
growth seems to be, at least partly, due to an earlier reac-
The clinical onset of puberty is preceded by reactiva- tivation of the HPG axis possibly driven by changes in
tion of the HPG axis leading to increasing circulating lev- body composition. However, the influence of adiposity
els of the gonadotropins and the sex steroid hormones on pubertal timing is still controversial in boys with obe-
[49]. Thus, if centrally mediated, one would expect the sity associated with both early [25] and late pubertal onset
secular trends in clinical onset of puberty to be paralleled [24]. This disparity may be related to differences in the
by secular trends towards declining age of the pubertal BMI cutoff used to define obesity as well as the degree of
gonadotropin surge. However, such data have not been adiposity in the reference groups in that both extremes of
available from previous population-based studies. In the the adiposity spectrum may be associated with a relative
Copenhagen Puberty Study, the majority of the partici- delay in pubertal timing [12, 24, 25].

Recent Secular Trends in Pubertal Horm Res Paediatr 2012;77:137–145 141

Timing
 Girls Boys
30 2006–08 10 2006–08
1991–93 1991–93
24 8

18 6

LH (IU/l)

LH (IU/l)
12 4

6 2

0 0
6 8 10 12 14 16 18 20 6 8 10 12 14 16 18 20

2.0 50
2006–08 2006–08
1991–93 1991–93
Fig. 4. Reproductive hormone levels ac- 1.6 40

Testosterone (nmol/l)
cording to chronological age in 1,276
Estradiol (μmol/l)

healthy girls and 965 healthy boys collect- 1.2 30

ed in the Copenhagen area in two periods:
1991–1993 and 2006–2008. LH and estra- 20
0.8
diol levels are presented in girls, and LH
and testosterone in boys. Black lines repre-
sent the median, 2.5th and 97.5th percen- 0.4 10
tiles. The 1991–1993 cohort is presented in
green and blue, and the 2006–2008 cohort 0 0
in purple and orange in girls and boys, re- 6 8 10 12 14 16 18 20 6 8 10 12 14 16 18 20
spectively. Modified with permission [10, Age (years) Age (years)
12].

Precocious Puberty prevalence in Denmark of approximately 0.2% in girls

and below 0.05% in boys [56]. However, the secular trends
In girls, PP is defined as attainment of breast or pubic towards earlier pubertal timing in the general population
hair development before the age of 8 years, whereas at- have been paralleled by an increase in the prevalence and
tainment of genital development, pubic hair development incidence of PP in girls (fig. 5) [13]. Although the inci-
or testicular enlargement of more than 3 ml before the age dence of gonadotropin-dependent PP is increasing, the
of 9 years defines PP in boys. In around 90% of cases in sudden increase in all variants of precocious pubertal dis-
published series [10, 13, 53], the precocious onset of pu- orders during the recent decade may be an indication that
berty is centrally mediated by an early reactivation of a greater proportion of early pubertal girls get medical
HPG axis, termed central PP (CPP). In addition to ad- attention than previously. Thus, higher referral rates
vanced pubertal development, patients with CPP present rather than a true increase in these conditions may play
with growth acceleration, advanced skeletal maturation a substantial role in the recently observed trend in PP.
and elevated gonadotropins during GnRH testing [54].
Although CPP is idiopathic in the majority of girls, 10– Definition of Pubertal Precocity – Is It Time for a
20% of girls and the majority of boys have an underlying Redefinition?
organic etiology. In most of these cases, CPP results from The age limits for the diagnosis of PP is classically de-
pathology within the hypothalamus [55], and brain MRI fined by the lower limit of the 95% prediction interval
is therefore generally indicated as part of the routine (equal to –2 SD or the 3rd percentile) based on the distri-
workup in all patients with CPP. bution of ages at normal puberty for a given population.
The prevalence of PP is about 10 times higher in girls Importantly, the recent decline in mean age at pubertal
than in boys with an estimated register-based population onset has resulted in a parallel decline in the lower age

142 Horm Res Paediatr 2012;77:137–145 Sørensen/Mouritsen/Aksglaede/Hagen/

Mogensen/Juul
limit of normality. In girls, but not boys, the 3rd percen-
tile is now far lower than the diagnostic age limit of pu- 90 ENV
80 PA
bertal precocity defined by the classical work by Marshall PT
and Tanner from the late 1960s [42, 57]. This fact has 70 ICPP

Number of girls
60
opened a lively debate among pediatric endocrinologist
50
concerning the necessity of a revision of the age limit for
40
what is considered pubertal precocity requiring further
30
diagnostic evaluation. Although the great majority of re-
20
cent data consistently indicate that age at pubertal onset 10
is becoming earlier in both Europe [10, 11] and the US [3, 0
6], extrapolation from these population-based findings to 1993 1995 1997 1999 2001 2003 2005 2007
redefine the age limit for evaluation of PP may not be ap- Year of referral
propriate. If the recent secular trends in puberty are driv-
en primarily by an increase in isolated gonadotropin-in-
Fig. 5. Number of girls per year diagnosed with early normal pu-
dependent thelarche, lowering of the age limit for evalu- berty (ENV), premature adrenarche (PA), premature thelarche
ation of PP will overlook some girls with true rapid (PT), and idiopathic CPP (ICPP) according to year of referral
progressive PP from the age of 6 or 7 years leading, if un- (1993–2008) in a single tertiary pediatric endocrine center. Repro-
treated, to menarche by age 8 or 9, which by population- duced with permission [13].
based standards will be 1–2 years below the 3rd percentile
for normal-timed menarche in both black and white girls.
Another point of concern for a lowering of the age lim-
it for evaluation of PP in girls addressed by many pediat- limit for referral based solely on trends in age at breast
ric endocrinologists is the possible misdiagnosis of po- development in the general population.
tentially treatable underlying pathology. In the wake
of the LWPES recommendations, several independent
groups have undertaken retrospective evaluations of pa- Conclusion
thology in girls with CPP with pubertal onset after the
age of 6 years. The general conclusion from these studies The trend towards earlier mean age at onset of breast
is that implementation of the LWPES recommendations development in girls is accompanied by a downward shift
will lead to misdiagnosis of CNS abnormalities in 2–30% in the entire age distribution at pubertal onset, resulting
of the girls, some of whom needing surgery and chemo- in a concomitant lowering of the lower limit of normality
therapy [15, 53, 58, 59]. In addition to intracranial pathol- of breast development. However, these findings are based
ogy, Midyett et al. [16] reported that 12% of the girls eval- on population-based studies of healthy girls who did not
uated for PP with pubertal onset after the age show associated secular trends in timing of the pubertal
of 6 years manifested pathologic endocrine conditions. LH and estradiol surges. Thus, it appears as if we may
However, two thirds of these patients presented with hy- primarily be witnessing a phenomenon of isolated gonad-
perinsulinemia that, although girls with CPP may have otropin-independent thelarche among our contempo-
an increased risk of insulin resistance [60], could be a rary girls. It remains to be seen whether or not this ear-
normal finding considering the high obesity prevalence lier breast development will advance the entire sequence
(45%) in that cohort. Thus, 5–10% of girls with CPP may of sexual maturation processes, and if it will have possible
be misdiagnosed if the age limit for evaluation is lowered long-term side effects in the majority of early maturing
according to the LWPES recommendations. girls, or only in the small subset of those with rapid pro-
Altogether, the cutoff values for ages at which diagnos- gressive pubertal development leading to early menarche.
tic evaluation is needed should not be lowered at present, Due to the risk of overlooking rapid progressive PP as well
as this would result in a failure to identify children with as the risk of misdiagnosing intracranial and other un-
rapid progressive PP as well as failure to detect underly- derlying pathology, we do not believe that the population-
ing pathology that would respond to early intervention. based limits of normality should be translated into revi-
The criteria for evaluation of PP should rely on addition- sion of age limits at which girls with PP should be referred
al evaluation of pubertal progression, skeletal maturation for diagnostic workup including brain MRI.
or growth tempo, rather than simply lowering the age

Recent Secular Trends in Pubertal Horm Res Paediatr 2012;77:137–145 143

Timing
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