Puberty: Physiology and Abnormalities, 1st ed. 2016

9. Timing of Puberty and Secular Trend in Human Maturation

Anastasios Papadimitriou 

(1)

Third Department of Pediatrics, ‘Attikon’ University Hospital, 1 Rimini Street, Haidari, Athens, 12462, Greece

Anastasios Papadimitriou

Email: anpapad@med.uoa.gr

Keywords

PubertyPubertal maturationSecular trendMenarcheOnset of pubertySpermarche

Introduction

Puberty is a milestone in the transition from the immature child to the mature and capable for reproduction adult. Puberty refers to the physical changes that occur as a result of the reactivation of the hypothalamic-pituitary-gonadal (HPG) axis resulting in gonadal estradiol and testosterone secretion, whereas adolescence refers not only to somatic but the psychological changes that occur as a consequence of the HPG axis activation. The HPG axis is transiently activated during early infancy followed by a long period of relative quiescence. The process of puberty lasts for 3–5 years, and adolescence may last 10 years or more.

The timing of pubertal onset has been related to public health issues, e.g., early onset of puberty has been related to metabolic syndrome , hence increased cardiovascular risk, breast cancer in women, all-cause mortality, and testicular cancer in men [14], whereas delayed puberty has been linked to osteoporosis [5]. Therefore, there is a continuous interest on the timing of pubertal onset in the various populations and whether the age that puberty begins is decreasing.

Definitions

Onset of puberty is defined in girls as the first appearance of breast tissue (breast budding) and in boys as the attainment of a testicular volume more than 3 mL. Breast development must be determined by palpation, to avoid misclassification of fat (lipomastia) as breast, when the examination is only visual. Testicular volume (TV) is reliably determined by the Prader orchidometer, a graded series of ellipsoid beads on a string [6], in experienced hands. Nevertheless, the more accurate method of determining TV is by ultrasonography (US) , because, in the measurements by US, scrotal skin and epididymis are not included [7].

Menarche is a girl’s first menstrual bleeding, and spermarche is the boy’s first conscious ejaculation, which is more appropriate to be called ejacularche that often occurs during sleep, i.e., nocturnal emission. Spermarche, i.e., the onset of sperm production, precedes ejacularche and is usually detected as spermatozoa in a morning urine specimen (spermaturia) [8].

Factors Influencing the Timing of Puberty

The various factors that are influencing the onset of puberty are covered in detail in other chapters of the book.

Here, within the limited space of this review, I refer briefly to the role of genetic and epigenetic, ethnic/racial, and environmental factors. Table 9.1 shows some of the main factors that influence the timing of puberty .

Table 9.1

Factors influencing the onset of puberty

Genetic and epigenetic

Effect

Boys

Girls

Mutations of ESR1

Normal puberty

Delayed puberty

KISS1 and KISSR1

Hypogonadotropic hypogonadism

Hypogonadotropic hypogonadism

MKRN3

Precocious puberty

Precocious puberty

SNP rs314276 of LIN28B

Earlier onset of puberty

Earlier onset of puberty/menarche

Polymorphism of FSHR-29AA

Later onset of puberty

Epigenetic changes in polycomb group proteins (Cbx7 and Eed)

Signal pubertal onset

Ethnic/racial differences

Black race

Early puberty/no effect

Early puberty/menarche

Environmental factors

Low socioeconomic status

Uncertain

Late menarche

Higher parental education

Uncertain

Early puberty

Absence of biological father

Uncertain

Early puberty

Urban environment

Uncertain

Early puberty

Adoption of Third World children

Inconsistent

Early puberty

Chronic stress (e.g., illness, wars)

Delayed puberty

Delayed puberty

Endocrine disruptors

Phthalates

Uncertain

Early puberty/no effect

Bisphenol A

Uncertain

Early puberty/no effect

Pesticides (DDT, DDE)

Uncertain

Early puberty/no effect

Genetic and Epigenetic

Although almost half of the variance in the age at menarche has been attributed to heritability [910], knowledge of the specific factors regulating the onset of puberty is limited. Rare mutations have been identified as the cause of disordered pubertal timing, e.g., ESR1KISS1KISSR1, and MKRN3; however, these genes do not seem to determine the timing of puberty in the population. Genome Wide Association Studies (GWAS) examining genetic variations using large numbers of data explain only about 15 % of the variance in menarcheal age [11]. It is notable that for a single nucleotide polymorphism rs314276 in intron 2 of LIN28B on chromosome 6, each major allele was associated with 0.12 years earlier menarche. In girls there was also association of this allele with earlier breast development and in boys with earlier voice breaking, suggesting earlier pubertal maturation . In line with early timing of puberty were the associations of LIN28B with a faster tempo of growth and shorter adult height in both sexes [12]. In a recent large-scale meta-analysis of 57 GWAS including data from 182.416 women, the authors found robust evidence for 123 signals at 106 genomic loci associated with age at menarche. Moreover, menarche signals were enriched in imprinted regions, with three loci (DLK1/WDR25MKRN3/MAGEL2, and KCNK9) demonstrating parent-of-origin specific associations concordant with known parental expression patterns [11]. Further analysis implicated retinoic acid and gamma-aminobutyric acid-B2 receptor signaling pathways as novel mechanisms regulating pubertal timing in humans.

The stronger genetic influence on pubertal onset in girls, so far, has been a polymorphism related to follicle-stimulating hormone receptor (FSHR) [13]. In girls homozygous for FSHR-29AA (reduced FSH receptor expression) pubertal onset occurred 7.4 months later than those with the common genotype variants FSHR-29GG+GA. Furthermore when FSHR-29GG+GA was combined with FSHB-211G>T (reduced FSH production), the age at pubertal onset increased with the number of minor alleles across the genotypes.

The role of epigenetic modification of genes in the control of pubertal onset has only recently been unraveled. Lomnizci et al. [14] demonstrated that increased promoter methylation and decreased expression of two polycomb group proteins (Cbx7 and Eed) leads to disinhibition of kiss1 expression signaling pubertal onset. In the same study administration of 5-azacytidine, a pharmacological inhibitor of DNA methylation , prevented the increase of Kiss1expression that occurs prior to pubertal onset, resulting in pubertal delay.

Ethnic/Racial Influences

Several studies have shown the existence of ethnic/racial differences in the timing of pubertal maturation or menarche. Most of these studies refer to children in the USA and have been performed mostly in girls.

In a longitudinal 10-year study, which begun in 1986–1987 [15], black or white girls were examined annually. Mean onset of puberty in the white girls was 10.2 and in the black girls was 9.6 years. In the same study the age at menarche was 12.6 and 12.0 years, for the white and black girls , respectively.

In the Bogalusa Heart Study, black girls experienced menarche, on average, at the age of 12.3 years, 3 months earlier than did white girls experiencing menarche at 12.6 years [16]. Anthropometric differences, such as weight and height, which could be a confounding factor were controlled for; however, menarche remained significantly earlier among black girls, suggesting that race is an independent factor of pubertal development and timing of menarche . Black girls present higher insulin response to a glucose challenge and also have increased IGF1 levels compared to white girls [17]. Probably these biological differences have a genetic basis and are related with the more advanced skeletal and sexual maturation of the black compared to the white girls.

Contrary to the girls, only a few studies evaluated the existence of ethnic differences in the timing of puberty in boys. In the NHANES III study, conducted by the National Center for Health Statistics between 1988 and 1994, the median age at onset of pubertal maturation was approximately 9.2 years for black boys, 10.0 years for white boys, and 10.3 years for Mexican American boys, suggesting that, as African American girls do, African American boys enter puberty earlier than their peers of other origins [18].

However, in another US study, two hundred and twelve practitioners across the USA, in 144 well-child care pediatric offices, collected, cross-sectionally, Tanner stage and TV data on 4131 boys [19]. The data were collected between 2005 and 2010. Mean ages for attainment of TVs of ≥3 mL were reported to be 9.95 years for white, 9.71 years for African American, and 9.63 years for Hispanic boys and for ≥4 mL were 11.46, 11.75, and 11.29 years, respectively. Therefore, the latter data do not support the suggestion that African American boys mature earlier than European American boys. In line with this is an older observation in American children in which no difference was found at a testicular volume of 3 mL that usually heralds the onset of puberty (indeed most boys had attained a testicular volume of 4 mL within the next 6 months) between black and white children [20].

Environmental Factors

Environmental factors that impose a health hazard to the human are numerous and include air, water and food quality, waste disposal, hazardous substances, unsafe public space, and conditions within the house, e.g., stressful family environment.

Environmental factors that have been related to the timing of puberty include socioeconomic factors, place of residence, and endocrine-disrupting chemicals. More studies refer to females, and furthermore the results on boys are inconsistent or do not show a clear impact of the environmental factors to pubertal timing . Girls from families of low socioeconomic status experience menarche later than girls from affluent families [2122]. Parental education has been associated with the timing of puberty, higher education related to earlier onset of puberty. The absence of biological father, especially in the first 5 years of life, is also related to earlier puberty, and the association becomes stronger when the absence of biological father is combined with the presence of a stepfather and a stressful family environment [2324]. The place of residence during childhood is also important for the timing of puberty, urban girls experiencing menarche earlier than rural girls [2526].

Adoption of Third World children in Western Europe has been related to early puberty, especially in girls. The early sexual maturation may be triggered by the catch-up growth that is the usual growth pattern of these children after undernutrion [27] or recovery from psychosocial deprivation [28].

On the other hand, chronic illnesses , conditions of war [29], and in general conditions related to chronic stress result in suppression of HPG axis and delay in pubertal onset.

Endocrine Disruptors

Endocrine disruptors or endocrine-disrupting chemicals (EDCs) are mainly man-made, exogenous compounds (chemicals) that can interfere with the activity of endogenous hormones or disturb hormone signaling systems. EDCs mimic or block hormone signaling through the relevant hormonal receptor or modulate the synthesis, metabolism, and binding or elimination of natural hormones. EDCs are mainly used in industry , as solvents/lubricants [polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), dioxins], plastics [bisphenol A (BPA)], plasticizers (phthalates), pesticides [methoxychlor, chlorpyrifos, dichlorodiphenyltrichloroethane (DDT)], fungicides (vinclozolin), and also as pharmaceutical agents [diethylstilbestrol (DES)] [30]. EDCs may also be made by nature, e.g., phytoestrogens that interfere with endogenous endocrine function are produced by plants.

EDCs may affect the reproductive system via peripheral actions. Endocrine disruptors may have estrogenic activity , e.g., BPA; thus, their action is exerted through estrogen receptor; others, e.g., vinclozolin, interact with the androgen receptor, while other EDCs, e.g., fadrozole and ketoconazole, inhibit aromatase or steroidogenesis, respectively. On the other hand EDCs may affect puberty via CNS regulation . Atrazine delays puberty, reducing circulating LH and prolactin, in Sprague-Dawley (SD) and Long-Evans hooded (LE) rats [31]; phthalates and PCBs have been associated with earlier breast development and menarche, respectively [32].

The most commonly used and studied endocrine-disrupting chemicals are phthalates, bisphenol A, and pesticides.

Human exposure to phthalates is extremely prevalent and may occur through oral, inhaled, and topical routes. In a study on 129 Danish children and adolescents, the authors determined the concentrations of 11 phthalate metabolites of five different phthalate diesters on 24 h urine samples [33]. They found that phthalate metabolites were detectable in the urine of almost all children; younger children and boys were more exposed than older children and girls. The effect of phthalate exposure on the timing of puberty is controversial. In Puerto Rico high phthalate levels have been linked to premature thelarche [34]. In a study of 725 healthy Danish schoolgirls, it was demonstrated that high phthalate excretion in urine was associated with delayed pubarche, but not thelarche, which suggests antiandrogenic actions of phthalate [35]. Similar results were obtained in a study of US girls [36]. Some studies report early or precocious puberty, whereas others do not find such an association [37]. Moreover, in a study performed in China, elevated levels of phthalates were associated with constitutional delay of growth and puberty [38]. Therefore more studies are warranted to explore the effect of phthalate exposure on pubertal timing.

BPA is found in plastics (e.g., bottles, food cans, Tupperware, etc.), humans being exposed mainly through food contamination from plastic packaging. BPA is the most commonly found estrogen-like endocrine disruptor in the environment. Although it has been shown, in experimental animals, that BPA advances puberty [39], results on humans are inconsistent. In a study of 1151 girls, BPA had no influence on breast development [40]; however, in a Turkish study idiopathic central precocious puberty was associated with higher levels of BPA than control girls [41]. Thus, more studies are needed to clarify the existence of an association between BPA and pubertal maturation.

Pesticides are classified in various classes, e.g., insecticides are used for killing insects, and herbicides and fungicides are used against unwanted plants and fungi, respectively. Pesticides enter the human body through water, air, and food, and also, they can pass from the mother to the fetus via placenta and to the infant through mother’s milk. Most of these substances cannot be broken down by the body, are lipophilic, and accumulate in adipose tissue, where they remain for long periods of time. The most widely studied pesticide compounds are DDT and its metabolite dichlorodiethyl dichloroethane (DDE) . Although the agricultural use of DDT has been banned worldwide, in some developing countries, it is still used against the mosquitoes, as vectors of malaria.

Vasiliu et al. reported decrease in menarcheal age to girls exposed in utero to DDE [42]. However, when weight at menarche was controlled for, the significance of the association disappeared. In a Danish study of mothers who worked in greenhouses in the first trimester of pregnancy , the mothers were prenatally categorized as exposed or unexposed to pesticides. The female offspring of the exposed greenhouse workers had a significantly decreased age at onset of breast development at 8.9 years, compared with 10.4 years in the unexposed, and 10.0 years in a Danish reference population [43]. In a study examining the prenatal DDT exposure in relation to anthropometric and pubertal measures in adolescent males, no associations between prenatal exposure to any of the DDT compounds and any pubertal measures were noted [44]. Adopted or immigrant girls in Belgium, who presented central precocious puberty (CPP) , had increased plasma levels of pesticides (DDE); thus, the authors suggested that CPP could be attributed to pesticide exposure [45]. However, other studies did not find an association between DDE levels and timing of menarche [46]. Also, in inner-city girls DDE , Pb, and dietary intakes of phytoestrogens were not significantly associated with breast stage [47].

The inconsistency of the results of the various studies examining the association of pesticides with onset of puberty makes imperative that more studies on the subject are needed.

Secular Trend in Human Maturation

Historical Data

One of the oldest inscriptions relating to age at menarche was from India, mainly by legislators, and they usually referred to upper-class girls . It is remarkable that from 500 BC until 500 AD, the age at menarche was reported to be 12 years [48].

At about the same time, the Greek philosopher and biologist Aristotle (384–322 BC) in his writings “Historia Animalium ” reported the age at menarche to occur at 14 years and that at the same age ejacularche occurred in boys. Other physicians of the Greek-Roman era, i.e., Soranus of Ephesus (second half of first century AD), Galen (129–199 AD), and Oribasius (325 ca 400 AD), the personal physician of Julian the Apostate, also reported that in the majority of girls, menarche occurred at 14 years. However, these writings should be considered with care, since the age at menarche of 14 years may be related to the traditional mystical number 7.

For Chinese female , life is dominated by the number 7, first teeth erupting at 7 months of age and puberty, as marked by menarche, at 14 years. For boys the dominant number was 8, teeth erupting at 8 months and puberty, presumably ejacularche, occurring at 16 years [49].

In the medieval years, the age at menarche is generally reported to be similar to the classical years, i.e., 14 years, with a range from 12–15 years [50].

The age at menarche started to delay at the beginning of the modern era, especially after the industrial revolution , due to deterioration of hygiene and increasing population density that resulted in the spread of diseases. From available data it is estimated that in the second half of the eighteenth century, menarche occurred at 15–16 years of age. By mid-nineteenth century, the age at menarche in France was 15 years, whereas in Scandinavia was 17 years, suggesting the existence of a north to south gradient in pubertal maturation [5152].

Girls

Onset of Puberty in Girls

In the twentieth century the improvement of the socioeconomic conditions and the hygiene of the population resulted in increased somatic growth and earlier pubertal maturation of the children. The latter was most clearly evident in the age at menarche, which decreased substantially during the previous century. Although there is an abundance of studies on menarche and its secular trend in many countries, the studies that report on the timing of onset of puberty, i.e., breast development-B2 (thelarche), are much fewer. As far as pubic hair development is concerned, most experts believe that the onset of pubic hair development (PH2) is highly variable, depending on the individual, ethnicity, and race; therefore, the data are insufficient to establish a secular trend for PH2 [53].

Most studies on the secular trends of the onset of puberty refer to American or European girls.

In a developed country like Denmark, in a study performed in Copenhagen, onset of puberty, i.e., B2, occurred significantly earlier in the year 2006 (estimated mean age 9.86 years) compared to 1991 (estimated mean age 10.88 years), the difference remaining significant after adjustment for BMI [54]. In the Netherlands in a study examining the secular trend in three time points, i.e., in 1965, 1980, and 1997, it was shown that there was a decrease in the age of B2 between 1965 and 1980, but afterward the trend tended to stabilize, and median B2 was 11.0 years in 1965, 10.54 in 1980, and 10.7 years in 1997 [55]. In Krakow, Poland, age of thelarche declined between 1983 and 2010 from 10.9 to 10.3 years, respectively, that may be related to the socioeconomic changes that took place in Poland in the late twentieth century [56]. In Istanbul, Turkey, in a transitional society , i.e., a society undergoing large socioeconomic changes, the age at B2 decreased from 10 years in 1973 to 9.65 in 2009 [57]. In Athens, Greece, our group, in the 1990s, performed two studies, one cross-sectional and one longitudinal , examining the age of onset of female puberty [58]. In the cross-sectional study in 1995, we reported mean age at B2 to occur at 10.3 years, and in the longitudinal study, from 1990 to 1997, median age of onset of puberty was 10.0 years, and mean age was 9.9 years. In a study of Athenian girls in 1979, breast development occurred at 10.6 years [59]. These studies suggest a secular trend toward earlier onset of puberty between 1979 and 1995.

In 1997 in the USA, Herman-Giddens et al. [60] published a study performed by the Pediatric Research in Office Settings (PROS) network aiming to determine, by inspection, Tanner stages for breast and pubic hair development in 3-year-old to 12-year-old girls. The authors collected data on more than 17,000 girls (90 % white and 10 % black). The main finding of the study was that the mean age of onset of B2 was 10.0 years in white and 8.9 years in black girls, with a similar trend for pubic hair appearance that was 10.5 years for white and 8.8 years for black girls. All these estimates were earlier than those of previous studies. In the small longitudinal study of Nicolson and Hanley [61], children born in Berkeley, California, in 1928 and 1929, were followed yearly and when 8 years old half yearly until they reached the age of 18 years. Mean age of breast development in this sample was at 10.6 years and of pubic hair 11.6 years. In the Bogalusa Heart Study (9/1973-5/1974) mean age (±2 SE) of breast development in white girls was 10.37 (0.21) years and in black girls 10.22 (0.25) [61].

Age at Menarche

The studies examining the secular trend of age at menarche in various populations are numerous. Some of these studies are shown in Table 9.2. In general, for the most part of the twentieth century and the beginning of the twenty-first century, there is a trend for earlier ages at menarche. A secular change for earlier menarche is still occurring in developing and also in developed countries, e.g., Canada [62], China [63], Denmark [54], India [64], Israel [65], Korea [66], South Africa [67], Spain [68], and the UK [69].

Table 9.2

Secular changes in the age at menarche (AAM)

 

Time period

AAM (years)

Time period

AAM (years)

References

Decreasing AAM

Canada

Year of birth <1933

13.2

Year of birth 1986–1990

12.5

[62]

China

Year of birth 1955–1960

15.7

Year of birth 1981–1985

14.7

[63]

India

Year of birth 1955–1964

13.8

Year of birth 1985–1989

13.6

[64]

Denmark

Year of study 1991

13.4

Year of study 2006

13.1

[54]

Israel

Year of birth 1969

13.4

Year of birth 1995

12.8

[65]

Korea

Year of birth 1920

16.8

Year of birth 1986

12.7

[66]

S. Africa (blacks)

Year of birth 1956

14.9

Year of birth 1990

12.4

[67]

UK

Year of birth 1945–1949

12.6

Year of birth 1990–1993

12.3

[69]

Slowing down or leveling off in AAM

USA

Year of birth 1980

12.3

Year of birth 1993

12.3

[72]

France

Year of study 1994

12.6

Year of study 2009–2010

12.5

[75]

Greece

Year of study 1996

12.27

Year of study 2006

12.29

[77]

Netherlands

Year of study 1997

13.15

Year of study 2009

13.05

[78]

In the USA, the mean age at menarche was more than 14 years in the nineteenth century [70], and in the NHANES III, in the late twentieth century (between 1988 and 1994) [71], it decreased to 12.43 years. The Fels Longitudinal Study of girls born in 1980 showed that menarche was at a slightly younger age at 12.34 years [72]. Comparing the data of NHANES III to those of NHES II/III [73], there was a decrease in menarcheal age of 4 months from 1963–1970 to 1988–1994. In the latest report on age at menarche in US girls [74], it was shown that girls born in 1993 had menarche at 12.3 years of age, at is similar to those born in 1980.

As in the latest report from the USA, and in some other countries, this trend is slowing down or has stabilized, e.g., France [75], Germany [76], Greece [77], and the Netherlands [78].

Furthermore, it is noteworthy that in Israel [65] and the UK [69], there is a recent decline in the age at menarche after decades of stabilization.

Menarche is often used as a proxy for the onset of puberty. However, studies from the USA and Denmark have shown that the decrease in onset of puberty (B2) is not accompanied by an analogous decrease in age at menarche. This discrepancy may be due to maturational tempo differences.

Maturational Tempo Differences and Age at Menarche

Early studies on the correlation between menarche and onset of puberty, in women born between 1920 and the 1960s, showed high correlations (0.64–0.86), whereas data from women born between 1977 and 1979 showed only a moderate correlation (0.37–0.38) [15]. An explanation of this may be a change in maturational tempo in girls born in the last part of the twentieth century. Several studies performed during the last two decades showed early-maturing girls to present a compensatory delay in pubertal progression [7981] that is associated with greater pubertal height gain and a longer period of pubertal growth, thus explaining the moderate correlation between onset of puberty and age at menarche.

Boys

Onset of Puberty in Boys

The studies referring to the onset of puberty of boys are much fewer than those referring to girls. This may be due to refusal of the boys to be examined in the genital area or because of less interest in male puberty reflecting less cultural awareness for male pubertal maturation compared with girls [53]. Therefore, the secular trend of pubertal onset is less well studied in boys. In general, whereas the secular trend for earlier maturation is well established in girls, that is not the case for boys.

A substantial number of studies do not show secular trends in male pubertal onset. In the Netherlands in a study on pubertal maturation between 1965 and 1997, the authors did not detect a secular trend after 1980, attainment of TV of 4 mL being at 11.5 years [55]. In Istanbul, Turkey, in a longitudinal study from 1989 to 1999, TV of 4 mL was attained at a mean age of 11.6 years, whereas pubic hair development was at 12.3 years [82]. In an older Turkish study of boys born between 1955 and 1960, pubic hair was reported to develop at 11.8 years (no TV was measured), indirectly suggesting no secular trend [83]. In Athens, Greece, we did not find a significant change in the attainment of genital stage 2 (G2) between 1996 and 2007–2009, mean ages of G2 being 11.4 and 11.3 years, respectively [84]. In the USA, an expert panel that examined in 2005 possible secular trends in boys’ puberty had the unanimous opinion that the data are insufficient to suggest or establish a trend for earlier puberty. This opinion was based on the lack of data quality, quantity, and marker reliability [53]. Many studies did not assess the more meaningful measure of pubertal onset, i.e., TV >3 mL. In 2012 the PROS network published their findings on male pubertal onset. The attainment of a TV of ≥4 mL was 11.46 for white, 11.75 for African American, and 11.29 for Hispanic boys and for PH2 was 11.47, 10.25, and 11.43 years, respectively. The authors concluded that testicular growth and pubic hair development were 6 months to 2 years earlier than in the past [19]. A secular trend for earlier onset of puberty was observed also in Copenhagen, Demark [85]. Between 2006–2008 and 1991–1993, mean onset of puberty decreased by 3 months, i.e., from 11.92 to the older to 11.66 years to the latest study.

Spermarche (Ejacularche)

If the data on pubertal onset in boys are relatively few, the age of the first conscious ejaculation (ejacularche) is scarcely examined. In boys, ejacularche may be considered analogous to menarche in girls. The term spermarche, in some studies, defines the first appearance of spermatozoa in urine samples (spermaturia), whereas other studies by spermarche define the first conscious ejaculation; however, the latter is best defined by the term ejacularche. Tanner in “Normal Growth and Growth assessment” [86] reports that ejacularche occurs about a year after the acceleration of penile growth, based on the work of Laron [87]. In their study Laron et al. found that despite a wide variation in the chronological age, the first ejaculation occurred, bone age, i.e., biological age, was 13.5 (±0.5) years, even in boys with delayed puberty.

In a longitudinal study , about 30 years ago, in Denmark [88], spermaturia occurred at a median age of 13.4 years (range 11.7–15.3 years), median TV being 11.5 mL (range 4.7–19.6 mL). In most boys spermaturia preceded peak height velocity. In a Mexican cross-sectional study, published in 1992, median age at spermaturia was 13.4 years, spermaturia occurring at a genital stage 2 [89], whereas in another Mexican study of teenagers and young adults (10–25 years of age) interviewed in 1987, the average age of ejacularche was 14 years [90]. In a Bulgarian study conducted in the 1990s, mean age of ejacularche was reported to occur at 13.27 (±1.08) [91]. In that study the authors reported a clear secular trend when their data were compared to studies of the year 1914, ejacularche occurring at 17 years, and of 1953, when ejacularche occurred at 15 years of age. In a Chinese study conducted in the year 1995, schoolchildren were interviewed about ejacularche. In urban males median age of ejacularche was 13.8 and in rural males 14.24 years [92]. In a study of urban Chinese boys conducted between 2003 and 2005, ejacularche was reported to occur at a median age of 14.05 years [93]. In 2004 it was reported that boys in Estonia presented ejacularche at a mean age of 13.35 (±0.99) years [94].

Therefore, from the limited available studies, it can be deduced that ejacularche in European boys occurs at around the age of 13.5 years. It is of historical interest that Aristotle wrote that, in Athenian boys in the fourth century BC, ejacularche occurred at 14 years of age!

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