Secondary Sexual Characteristics in Boys: Data from the Pediatric Research in Ofﬁce Settings Network

Secondary Sexual Characteristics in Boys: Data From the Pediatric Research in Ofﬁce Settings Network

WHAT’S KNOWN ON THIS SUBJECT: Recent investigations of AUTHORS: Marcia E. Herman-Giddens, PA, MPH, DrPH,a pubertal onset in US girls suggest earlier maturation. The Jennifer Steffes, MSW,b Donna Harris, MA,b Eric Slora, situation for US boys is unknown, and existing investigations are PhD,b Michael Hussey, MS,c Steven A. Dowshen, MD,d , , outdated and lack information on a key physical marker of male Richard Wasserman, MD, MPH,b e Janet R. Serwint, MD,f g h,i j puberty: testicular enlargement. Lynn Smitherman, MD, and Edward O. Reiter, MD Departments of aMaternal and Child Health, and cBiostatistics, WHAT THIS STUDY ADDS: US boys appear to be developing Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; bPediatric secondary sexual characteristics and achieving testicular Research in Office Settings, Department of Research, American enlargement 6 months to 2 years earlier than commonly used Academy of Pediatrics, Elk Grove Village, Illinois; dDepartment of norms, with African American boys entering Tanner stages 2 to 4 Pediatrics, Alfred I. DuPont Hospital for Children, Wilmington, earlier than white or Hispanic boys. Delaware; eDepartment of Pediatrics, University of Vermont, College of Medicine, Burlington, Vermont; fDepartment of Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, Maryland; gContinuity Research Network, Academic Pediatric Association, McLean, Virginia; hChildren’s Hospital of Michigan, Wayne State University School of Medicine/Detroit Medical Center, Detroit, Michigan; iNMA PedsNet, National Medical abstract Association, Silver Spring, Maryland; and jBaystate Children’s BACKGROUND: Data from racially and ethnically diverse US boys are Hospital, Tufts University School of Medicine, Springfield, needed to determine ages of onset of secondary sexual character- Massachusetts istics and examine secular trends. Current international studies sug- KEY WORDS secondary sexual characteristics, growth and development, gest earlier puberty in boys than previous studies, following recent Tanner staging, testicular volume, PROS, secular changes, trend in girls. puberty METHODS: Two hundred and twelve practitioners collected Tanner ABBREVIATIONS stage and testicular volume data on 4131 boys seen for well-child AAP—American Academy of Pediatrics CI—confidence interval care in 144 pediatric offices across the United States. Data were HHANES—Hispanic Health and Examination Survey analyzed for prevalence and mean ages of onset of sexual maturity NHANES—National Health and Nutrition Examination Survey markers. PROS—Pediatric Research in Office Settings SSCIB—Secondary Sexual Characteristics in Boys RESULTS: Mean ages for onset of Tanner 2 genital development for non- Dr Herman-Giddens is the principal investigator and primary Hispanic white, African American, and Hispanic boys were 10.14, 9.14, author; Dr Reiter is the co-principal investigator; Dr Reiter, Ms and 10.04 years and for stage 2 pubic hair, 11.47, 10.25, and 11.43 years Steffes, Ms Harris, Dr Slora, and Dr Wasserman have made respectively. Mean years for achieving testicular volumes of $3mL substantial contributions to the conception and design of this study, the acquisition of data, participated in drafting and were 9.95 for white, 9.71 for African American, and 9.63 for Hispanic critically revising this article for intellectual content, and given boys; and for $4 mL were 11.46, 11.75, and 11.29 respectively. African final approval of the version to be published; Mr Hussey, Dr American boys showed earlier (P , .0001) mean ages for stage 2 to 4 Serwint, and Dr Smitherman have made substantial contributions to the analysis and interpretation of data, genital development and stage 2 to 4 pubic hair than white and participated in drafting and critically revising this article for Hispanic boys. No statistical differences were observed between intellectual content, and given final approval of the version to be white and Hispanic boys. published; and Dr Dowshen has made substantial contributions to the conception and design of this study, interpretation of CONCLUSIONS: Observed mean ages of beginning genital and pubic data, participated in drafting and critically revising this article hair growth and early testicular volumes were 6 months to 2 years for intellectual content, and given final approval of the version to earlier than in past studies, depending on the characteristic and race/ be published. ethnicity. The causes and public health implications of this apparent shift in US boys to a lower age of onset for the development of (Continued on last page) secondary sexual characteristics in US boys needs further exploration. Pediatrics 2012;130:e1058–e1068

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The secular trend toward ayoungerage METHODS through 16 years of age presenting for of onset of puberty in girls in many Characteristics of Practice well-child care for eligibility; each en- countries is now generally accepted.1–3 Participants rolled up to 30 consecutive boys (15 from An expert panel convened in 2003 by 6–12 years of age and 15 from 13–16) Serono Symposia International, Inc, Clinicians were recruited from PROS from English- or Spanish-speaking fami- concluded that US girls were entering practices, the National Medical Asso- lies. Informed consent was obtained puberty at an earlier age than 40 years ciation Pediatric Research Network, from parents/guardians and assent and the Academic Pediatric Associa- ago.1 One of the key studies leading to from boys 7 and older before examination’s Continuity Research Network. this conclusion, conducted by the tion. Data for each subject were collected Participating clinicians comprised 196 American Academy of Pediatrics (AAP), on a form with numbered drawings and (93%) pediatricians, 1 family medicine found girls were typically developing verbal anchors to maximize accuracy. physician, and 15 (7%) nurse practi- about a year earlier than previously The physical examination included tioners. Practices from 41 states and 1 assumed.4 For boys, the panel con- height and weight, using each clini- Canadian province enrolled subjects cluded secular evidence was in- cian’soffice equipment, Tanner staging, between July 2005 and February 2010. sufficient and further studies were testicular volume measurement from 1 Seventeen percent of practices were needed. The most recent data on US through 4 mL, and breast palpation for located in the Midwest, 24% in the boys comes from several analyses of gynecomastia. Testicular volume was Northeast, 31% in the South, and 28% in the National Health and Nutrition collected for each testis as a categori- the West. Approval was obtained from – cal variable: #1, 2, 3, or $4 mL. Examination Survey (NHANES) III 1988 the AAP’s Institutional Review Board 19941,5–7; however, the data are 20 Examiners graded down the Tanner and 54 local institutional review boards stage or testis volume if either years old, the accuracy of the affiliated with participating practices. genital staging has been questioned, appeared to fall between categories. Additional demographic data were and testicular volumes were not Data Collection Process obtained.5,8,9 No recent studies repre- ascertained by observation, question- sentative of US boys or with large Before the main study, Secondary Sex- ing, and medical chart review. ual Characteristics in Boys (SSCIB), we numbers in varied locales have been established trained clinicians’ inter- published. Data on male puberty are Data Analysis rater reliability for Tanner staging and more difficult to obtain than female orchidometry.10 Tanner staging is a 5- We defined continuous age (years) as data because of the absence of an stage visual method for assessing the number of days between the month easily determined marker, such as development of secondary sexual of birth, (assuming the subject was menarche. Male pubertal stages are characteristics (genital and pubic hair born on the first of the month), and the harder to assess visually than girls’ growth for males) from prepubertal examination date divided by 365.25. stages, and orchidometry, an intrusive (stage 1) to fully mature (stage 5).11 When necessary, continuous age was procedure, is not part of well-child Using the study training manual,12 categorized as age rounded to the exams. participating clinicians learned Tanner nearest year. We classified subjects as Consequently, the AAP’s Pediatric staging and how to use a Prader African American if African American Research in Office Settings (PROS) orchidometer modified to contain only was indicated on the study form (re- practice-based research network un- the 1-mL to 4-mL beads. Clinicians gardless of any other race/ethnicity dertook this cross-sectional study to demonstrated competency by passing indication), Hispanic if Hispanic eth- determine the current ages of onset of a question-and-photograph qualifying nicity was indicated (regardless of any sexual maturity stages 2 to 5 and early examination. Intraclass correlations in other indication other than African testicular volumes in US boys seen for the clinical setting, where 2 practi- American), and white if only white was well-child care and to assess whether tioners in 8 practices rated a total of 79 indicated. there has been a shift in what is seen in boys, ranged from 0.61 for left testis We calculated descriptive statistics, office practice as compared with older size to 0.94 for pubic hair stage (all with exact binomial 95% confidence studies. Puberty is complex, including significant at P , .001), which indicate intervals (CIs) for prevalence of Tanner many dynamic components. This study moderate to substantial agreement stage2orgreaterpubichairandgenital was designed to report only physical depending on the variable being mea- development within each age category. changes, and not hormonal or other sured.10 For the main study, SSCIB, 212 We used stratified Mantel-Haenszel changes. qualifying clinicians screened boys 6 row mean score statistics to assess

PEDIATRICS Volume 130, Number 5, November 2012 e1059 Downloaded from www.aappublications.org/news by guest on September 26, 2021 homogeneity of prevalences by race/ ethnicity adjusted for age group. Median ages and SDs for transition into Tanner stages 2 to 5 were estimated by using probit regression, which links a linear combination of covariates to the cumulative normal probability of having achieved a stage. In probit analysis, the median age is assumed to equal the mean. For testicular volume analysis, we used the larger of the testes if there was a right-left difference.8 For each outcome, the probit model adjusted for continuous age, categorical race/ethnicity (ref- FIGURE 1 erence group: whites), and their Derivation of the SSCIB study population. interaction. Model coefficients were used to jointly test (a = 0.05) for equality of the mean ages of transition TABLE 1 Demographic and Clinical Characteristics of Study Subjects by Race/Ethnicity across the 3 race/ethnicity groups. Characteristic White African American Hispanic Pairwise comparisons of race/ethnicity groups were conducted with Bonfer- n (%) n (%) n (%) roni correction for multiple testing (ie, Payment status significance level a = 0.05/3 = 0.017). Medicaid 349 (17.5) 673 (65.9) 607 (63.0) Insurance 1618 (80.9) 340 (33.3) 333 (34.6) We calculated 95% CIs for the mean Self-pay 32 (1.6) 9 (0.8) 23 (2.4) ages of transition using Fieller’s Theo- Total 1999 1022 963 rem.13 All analyses used SAS 9.2 (SAS Chronic disease None 1691 (81.8) 775 (73.3) 806 (80.7) Institute, Inc, Cary, NC). Asthma only 137 (6.6) 149 (14.1) 82 (8.2) Other only 217 (10.5) 115 (10.9) 101 (10.1) RESULTS Asthma and other 22 (1.1) 18 (1.7) 10 (1.0) Total 2067 1057 999 We enrolled 5355 participants from 144 Chronic disease and medications None 1647 (79.8) 756 (71.7) 796 (79.9) sites between 2005 and 2010. After ex- Disease, no chronic medications 43 (2.1) 16 (1.5) 9 (0.9) clusion for chronic conditions or Medication, no chronic diseases 196 (9.5) 151 (14.2) 119 (11.9) medications that could affect puberty, Chronic diseases and chronic medications 179 (8.6) 134 (12.6) 73 (7.3) missing data, or “other racial” cate- Total 2065 1060 997 History of genital abnormalities gory, 4131 boys remained for analysis None 1961 (95.9) 1011 (96.8) 957 (97.9) (Fig 1). Of these, 2070 (50%) were Undescended testes 28 (1.4) 13 (1.3) 8 (0.8) classified as white, 1062 (26%) African Hypospadias 12 (0.6) 3 (0.3) 2 (0.2) Varicocele 16 (0.8) 3 (0.3) 4 (0.4) American, and 999 (24%) Hispanic. Undescended testes+hypospadias 3 (0.2) 1 (0.1) 0 (0) Demographic and clinical character- Other 26 (1.1) 12 (1.2) 7 (0.7) istics of the study population are pre- Total 2046 1043 978 sented in Table 1. There were 147 missing values for payment status, 8 missing for chronic disease, and 64 missing for history of genital abnormalities. Fig 2 shows the proportion of boys (95% CIs) entering Tanner stage 2 or greater genital development and pubic boys had higher proportions at a given Table 2 presents estimates of the mean hair growth by race/ethnicity and age. age for both genital and pubic hair age of transition to stages 2 to 5 for Adjusted for age, the proportion for development than white (both P , genital development and pubic hair both genital and pubic hair de- .001) and Hispanic boys (both P , growth. Entry into stage 2 genital development was found to be statistically .001), but white and Hispanic boys velopment occurred at 10.14 years for different among the 3 race/ethnicity showed no difference (P = .54 and P = white boys, 9.14 for African American groups (P , .001). African American .16, respectively). boys, and 10.04 for Hispanic boys.

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Overall, these were statistically different (P , .0001). Pairwise differences were found between African American and white boys (P , .0001), African Ameri- can and Hispanic boys (P , .001), but not between white and Hispanic boys (P = .48). For pubic hair, mean ages of entry into stage 2 were 11.47, 10.25, and 11.43 years respectively; overall, these were statistically different (P , .0001). Pairwise differences were found between African American and white boys (P , .001), and African American and Hispanic boys (P , .001), but not between white and Hispanic boys (P =.69). Because earlier pubertal studies assessing testicular volume have used volumes of 3 mL, $3 mL, .3 mL, and $4mL8,14–17 as indicative of central pubertal take-off, we present mean ages of transition for both $3 mL and $4 mL (Table 2). Data on Cincinnati boys15 and Swedish boys16 show that the transition from 2 to 3 mL indicates pubertal take-off. White boys in this study reached a mean age of transition to 3 mL at 9.95 years, African American boys at 9.71, and Hispanic boys at 9.63, with no significant difference (P = .11). Mean ages for reaching volumes of $4 mL were 11.46, 11.75, and 11.29 years, respectively. Overall, these were found to be statistically different (P = .008), with pairwise significance only between African American and Hispanic boys (P = .002). Data on progression to full sexual maturity present a slightly different pattern. For stages 3 and 4, statistical differences by race/ethnicity were observed, but not for stage 5. Pairwise differencesbetweenwhiteandHispanic boys were found for stages 3 and 4 pubic hair and stage 4 genital development. Estimated ages for entry intostage5(sexualmaturity)forgenital FIGURE 2 development were 15.57, 15.51, and Percentages (95% confidence intervals) of white non-Hispanic, African American non-Hispanic, and Hispanic boys with secondary sexual characteristics at sexual maturity Stage 2 or greater. 15.58 years, and 15.83, 15.72, and 15.89 for pubic hair for white, African Amer- ican, and Hispanic boys, respectively.

PEDIATRICS Volume 130, Number 5, November 2012 e1061 Downloaded from www.aappublications.org/news by guest on September 26, 2021 TABLE 2 Median (Mean) Ages of Transition for Secondary Sexual Characteristics and Testicular increase in BMI, and that existing BMI Volume Among White Non-Hispanic, African American Non-Hispanic, and Hispanic Boys standards for youth are based on Median, y SD 95% CI P value of Overall chronologic age, our cross-sectional Race/Ethnicity Differences data limit the assessment of cause- Genital development. and-effect relationships between BMI Stage 2 ,.0001 White 10.14 2.18 (9.97–10.31) and pubertal timing. African American 9.14 2.10 (8.88–9.39) Hispanic 10.04 1.83 (9.81–10.26) Stage 3 ,.0001 DISCUSSION White 12.49 1.44 (12.36–12.61) African American 11.58 1.65 (11.38–11.77) We observed that onset of secondary Hispanic 12.31 1.18 (12.14–12.47) sexual characteristics in US boys as Stage 4 ,.0001 seen in office practice appears to occur White 13.72 1.23 (13.61–13.83) African American 13.04 1.72 (12.85–13.23) earlier than in previous US studies and Hispanic 13.45 1.37 (13.28–13.61) the 1969 British study commonly used Stage 5 .9368 for pubertal norms.1,11 In addition, we – White 15.57 1.53 (15.42 15.73) found significant differences in the age African American 15.51 2.33 (15.21–15.87) Hispanic 15.58 1.64 (15.34–15.86) of onset of stage 2 genital and pubic Pubic hair hair growth between African American Stage 2 ,.0001 boys as compared with white and His- White 11.47 1.62 (11.33–11.61) African American 10.25 1.79 (10.03–10.46) panic boys and transition to testicular Hispanic 11.43 1.53 (11.23–11.62) volumes $4 mL (but not 3 mL). The Stage 3 ,.0001 meaning of this finding is unclear, as no White 12.89 1.18 (12.77–12.99) African American 11.79 1.56 (11.60–11.97) existing studies inform differences in Hispanic 12.57 1.15 (12.41–12.73) mean testicular size at given ages, by Stage 4 ,.0001 race/ethnicity, and sexual maturity – White 13.76 1.23 (13.65 13.87) stage; or in racial/ethnic differences in African American 13.06 1.67 (12.87–13.24) Hispanic 13.38 1.22 (13.22–13.54) the rate of advancement through the Stage 5 .6772 Tanner stages over time. White 15.83 1.49 (15.68–16.01) African American 15.72 1.97 (15.44–16.05) Of consequence are the differences we Hispanic 15.89 1.58 (15.64–16.22) found comparing our results with the Testicular volume 40-year-old data from Marshall and $3 mL .1109 ’ White 9.95 2.44 (9.76–10.13) Tanners landmark study on 228 white African American 9.71 2.43 (9.43–9.96) institutionalized boys in London.11 Hispanic 9.63 2.39 (9.36–9.89) White boys in our study entered stage 2 $ 4 mL .0079 genital growth 1.5 years earlier than White 11.46 1.97 (11.30–11.62) African American 11.75 1.83 (11.54–11.95) the British boys (10.14 vs 11.60 years of Hispanic 11.29 1.83 (11.07–11.50) age). Comparing ages of onset of stage 2 pubic hair growth from the British study (estimated at 13.4 years of age) Table 3 shows the ages of onset of BMI and ages of onset of sexual matu- is not possible because, as the authors secondary sexual characteristics from rity stages. Pooling race/ethnicity (be- stated, the age “was not accurately the Marshall and Tanner study, earlier cause of small sample size) and determined,” because assessments US studies, and our own. In particular, controlling for age, boys with BMI were from photographs.11 Their ob- SSCIB white and Hispanic boys entered ,15th percentile had later mean ages servation for entry into stage 3 pubic stage 2 genitalia 1.5 years earlier than of transition to stages 2 to 4 for genital hair, 13.9 years, is likely more reliable, the boys studied by Marshall and Tan- and pubic hair growth than boys with as stage 3 hair would be visible in ner. African American boys are more BMI .85th percentile (data not shown). photographs. White SSCIB study sub- than 2 years earlier. No other comparisons for stages or BMI jects entered stage 3 pubic hair de- Because data are conflicting on the categories were significantly different. It velopment at a mean of 12.89 years, effect of obesity on boys’ puberty,9,18–20 must be noted that because pubertal a full year earlier. For stage 2 pubic we examined relationships between development itself is associated with an hair, US studies from 1948 to 1995

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TABLE 3 Ages of Pubertal Events in Males in US and the British Marshall and Tanner Studies Study/ Data Type Country Subjects Age Mean Age, y Authors Collected, of Range, $ $ Year Span Study y TV 3mL TV 4mL G2 G3 G4 G5 PH2 PH3 PH4 PH5 Marshall 1950s– Mixed England 228 White $8 __ __ 11.6 White 12.9 White 13.8 White 14.9 White __ 13.9 14.4 White 15.2 White and 1970s Tanner11 Fels 1930s– L United 59 White 9–21 __ __ 11.5 White 12.7 White 13.4 White 17.3 White 12.2 White 13.3 13.9 White 16.1 White Downloaded from Institute21 1940s States NHES II/III22 1963– C-S United 3047 White 12–17 __ __ “similar to Marshall & Tanner, white and “similar to Marshall & Tanner, white and 1970 States African American” African American” Lee Study38 1969– L United 36 Not 9–17 __ __ 11.9 White 13.2 White 14.3 White 15.1 White 12.3 White 13.9 14.7 White 15.3 White 1974 States clearly speciﬁed www.aappublications.org/news Bogalusa 1973– C-S United 1153 White; 5–14 __ __ 11.8 White; ______12.5 White; ______Heart 1974 States 676 11.2 11.7 Study23 African African African American American American HHANES24 1982– C-S United 704 Mexican 10–17 __ __ 12.4 Mexican 13.5 14.6 16.3 Mexican 12.8 Mexican 13.6 Mexican 14.6 Mexican 16.1 Mexican 1984 States American American Mexican Mexican American American American American American American American NHANES III5 1988– — United 536 White; 8–19 __ __ 10.1 White; 12.4 White; 13.5 White; 15.9 White; 12.0 White; 12.6 White; 13.5 White; 15.7 White; 1994 States 797 9.5 African 11.8 13.4 14.9 11.2 12.5 13.7 15.4 African American; African African African African African African African byguest on September26, 2021 American; 10.4 American; American; American; American; American; American; American; 781 Mexican 12.5 13.7 15.7 12.3 13.1 14.1 15.8 Mexican American Mexican Mexican Mexican Mexican Mexican Mexican Mexican American American American American American American American American Biro Study15 1984– L United 278 White; 10–18 12.18 ______12.8 White/ 13.7 White/ 14.6 White/ 15.2 White/ 1987 States 237 White; African African African African African 12.18 American American American American American African American Susman 2000– L United 364 White; 9.5– __ __ 10.4 White; 12.4 White; 13.6 White; 14.9 White; 11.5 White; 12.8 White; 13.7 White; 15.1 White; Study25 2006 States 63 African 15.5 9.6 African 11.6 12.8 14.3 10.5 11.9 13.0 14.5 African American American African African African African African African American American American American American American American SSCIB 2005– C-S United 2070 White; 6–16 9.95 White; 11.46 10.14 White; 12.49 White; 13.72 White; 15.57 White; 11.47 White; 12.89 White; 13.76 White; 15.83 White; 2010 States 1062 9.71 White; 9.14 11.58 13.04 15.51 10.25 11.79 13.06 15.72 African African 11.75 African African African African African African African African American; American; African American; American; American; American; American; American; American; American; 999 9.63 American; 10.04 12.31 13.45 15.58 11.43 12.57 13.38 15.89 Hispanic Hispanic 11.29 Hispanic Hispanic Hispanic Hispanic Hispanic Hispanic Hispanic Hispanic

Hispanic ARTICLE

e1063 C-S, cross-sectional; G, genital; L, longitudinal; NHES, National Health Examination Survey; PH, pubic hair; TV, testicular volume. found a mean age of onset from 12.0 to found very early onset of genital stage to measure testicular volumes on 12.8 years of age5–7,15,21–23 for white 2 for all groups and noted that the 2- widely distributed boys, it can serve as boys. Results from SSCIB boys demon- year span between genital stage 2 and a baseline for future studies. strate this is occurring 6 months to pubic hair stage 2 was longer than that We also note the pattern presented by a year earlier than previously repor- found in any other puberty study. Thus, our data on progression to stage 5 ted. genital Tanner stage misclassification genital development and pubic hair Although comparison of ourresultswith may have occurred and the genital data growth indicating sexual maturity. Our those of earlier studies is limited be- may be unreliable. Stage 2 pubic hair subjects reached stage 5 at ages 15.7 to cause of lack of early data on minorities onset for Mexican American boys be- 15.8 forall racial/ethnic groups, similar and differences in methodologies, so- tween HHANES and NHANES III declined to the NHANES III data5; however, our cioeconomic status, age at enrollment, from 12.8 to 12.3 years. SSCIB Hispanic stage 5 probit model estimates (in- and small numbers of subjects in most boys reached stage 2 pubic hair at cluding comparisons of race/ethnicity) studies,1,4,18 the 6-month to 2-year ear- a mean of 11.43 years of age. Non- should be interpreted with caution lier development of secondary sexual Hispanic white and African American because they are artificially bounded characteristics or testicular enlarge- boys in SSCIB reached stage 2 pubic by SSCIB’s maximum enrollment age of ment as documented in our study is hair 0.53 and 0.95 years earlier than 16 years. It is interesting that the 2010 notable. Few older studies on African the NHANES III boys. Comparisons of US longitudinal study found boys’ age American or Hispanic boys exist. Results pubic hair stages should be more re- for genital maturity to be 14.9 and 14.3 from the 40-year-old nationally repre- liable, as assessment of pubic hair is for white and African American boys, sentative US Health Examination Survey, not as subjective as that of genital de- respectively.25 Cycle III, on African American boys were velopment. Our findings are also simi- The strengths of the PROS study include stated to be “comparable to the mean lar to a recent longitudinal puberty its large sample size and broad geo- ages in Marshall and Tanner’sdataon study that included 364 white and 63 graphical and minority patient repre- white boys.”22 Foster et al,23 in a study 35 African American boys (Table 3).25 sentation. In addition, observations years ago, found African American boys Very few European or US studies have were made only on well boys in primary in Louisiana began genital and pubic included testicular volumes. Largo and care sites by trained pediatricians and hair development at 11.2 and 11.7 years Prader’s landmark 198314 longitudinal other clinicians. Testicular volumes as compared with our ages of 9.14 and study on white Swiss boys proposed were measured through 4 mL. 10.25. testicular volume of 3 mL as the most The study has several limitations. Our The only previous US studies on His- accurate sign of central pubertal take- convenience sample of US boys seen in panic boys involved Mexican American off based on their earlier work, later pediatric offices for well-child care is boys: the Hispanic Health and Exami- confirmed by the Cincinnati15 and not a statistically representative sam- nation Survey (HHANES), 1982 to 1984, Swedish studies.16 Boys in the Swiss ple of the US population. The study and NHANES III, 1988 to 1992.5–7,24 Be- study were a mean age of 11.2 at gen- results could be questioned if the boys cause we enrolled Hispanic boys with- ital stage 2 and 11.8 at a testicular in our study were biologically different out regard to country of origin, direct volume of 3 mL. The study by Biro et al15 from boys in the US population; how- comparison may not be valid. HHANES is the only US puberty study that ever, there is no plausible reason that and NHANES III found attainment of gen- reported testicular volumes. Their would support this contention. Because ital stage 2 declined from 12.4 to 10.4 subjects, studied from 1984 to 1987 these data are cross-sectional, statis- years of age over a 10-year period, al- (Frank M. Biro, MD, personal commu- tical methods allow for only the esti- though the accuracy of the latter’sgenital nication, 2010), had a mean age of mation of mean ages of transition into data has been questioned as discussed 12.18 years when reaching a volume of the sexual maturity stages. Longitudi- in the following paragraph.5–7,24 SSCIB 3 mL, with no differences between the nal data are required to assess du- Hispanic boys entered stage 2 genital white and African American boys. ration, peak height velocity, and development at 10.04 years. SSCIB white and African American boys relationships between duration and Findings for genital data between the were 2.23 and 2.47 years younger, re- timing of pubertal stages. Population- PROS study and NHANES III are similar; spectively. Recent data from Denmark based longitudinal studies in the however, it should be noted that several also report a decline in age for United States have not been conducted authors have questioned the accuracy achieving a testicular volume .3 mL.8 because of methodological challenges of the NHANES III results,5,8,9,18 which Because our study is the first US study and expense. Our age calculations may

e1064 HERMAN-GIDDENS et al Downloaded from www.aappublications.org/news by guest on September 26, 2021 ARTICLE lack precision because, to protect pri- ular volume .3 mL more than 3 ACKNOWLEDGMENTS vacy, we could not collect the day of months earlier now than 15 years ago. The pediatric practices that partici- birth. This, however, is unlikely to have Our findings are somewhat surprising, pated in this study are listed by Ameri- introduced meaningful differences. given that factors associated with ear- can Academy of Pediatrics chapter. The Our training in sexual maturity staging lier physical development in girls, such listing of participants’ names does not and orchidometer use was designed as overweight and certain endocrine imply their endorsement of the data with the input of several pediatric disrupters,34 are not known to be as- and conclusions. Alabama: Greenvale endocrinologists and accomplished sociated with earlier development in Pediatrics–Alabaster (Alabaster), Phy- through an instruction manual with boys and could even be theorized to sicians to Children (Montgomery), Uni- photographs and explanatory and in- have a delaying effect.2,35 Our data do versity of Alabama at Birmingham structive text. As previously described, not allow for an analysis of the possible School of Medicine, Huntsville Campus fi testing ensured staging pro ciency underlying mechanisms of these ob- (Huntsville). Alaska: Anchorage Pediat- among qualifying clinicians. We are served decreases in the apparent age of ric Group LLC (Anchorage). California-1: aware of no large US study that has so onset of secondary sexual character- Palo Alto Medical Foundation (Los carefully documented its training istics as assessed by physical exami- Altos), Palo Alto Medical Foundation methods with a manual and testing, nation. They do, however, demonstrate (Palo Alto), Palo Alto Medical Founda- and shown interrater reliability among the importance in the physical exami- tion (Mountain View), Pediatric and Ad- a sample of those trained. Although it nation of boys of observing the ontogeny olescent Medical Associates of the would have been ideal to have assess- Pacific Coast Inc (Salinas), Practice of of changes in testicular volumes along ments completed by pediatric endo- Anita Tolentino-Macaraeg MD (Hollister), with the stage of pubic hair growth. For crinologists with extensive experience Practice of Razia Sheikh MD (Fresno), example, in a 7-year-old, the presence of in sexual maturity staging, this was not Shasta Community Health Center pubic hair with concomitant testicular feasible in a study of thousands of (Redding); California-2: Boulevard Pedi- volume increase needs close scrutiny nonreferred children across 41 states. atrics Medical Group Inc (Encino), and endocrinologic evaluation to be Testicular volumes were assessed as Children’s Health Center at Mattel sure that true sexual precocity is not #1, 2, 3, or $4 mL; therefore, data Children’s Hospital University of Cali- occurring. In the absence of increased from studies that used .3 mL but ,4 fornia Los Angeles (Los Angeles), Loma testicular volume or systemic changes mL rather than $3mLor$4mLas Linda University Health Care (Moreno of androgenization, the more likely their criteria for central pubertal take- Valley), University of California Los process in this example would be that of off are not strictly comparable. Ultra- Angeles Manhattan Beach Pediatrics “benign” premature adrenarche. sound, regarded as a more precise (Manhattan Beach), University of Cali- method for measuring testes,26,27 is not Current environmental factors, in- fornia Los Angeles West Los Angeles practical for large-scale studies and is cludingexposuretochemicals,changes Office (Los Angeles); California-3: Clini- not part of the usual pediatric exami- in diet, less physical activity, and other cas de Salud del Pueblo, Calexico Clinic nation.28 Volume comparisons with the modern lifestyle changes and expo- (Calexico); California-4: Edinger Medi- Prader orchidometer have been shown sures may be related to this apparent cal Group and Research Center Inc to be reasonably accurate.27 rapid decrease in the age of onset of (Fountain Valley), Southern Orange In conclusion, our data suggest that US secondary sexual characteristics and County Pediatric Associates (Rancho boys are beginning genital and pubic may not reflect healthy conditions.36,37 Santa Margarita). Colorado: Children’s hair growth earlier than several deca- Psychological, emotional, and behav- Clinic of Pueblo PC (Pueblo), Denver des ago in concordance with recent ioral affects of earlier sexual maturity Pediatrics (Thornton), Rocky Mountain reports on girls.1 These data are con- may be pivotal, given the current phe- Pediatrics PC (Lakewood), Rocky Moun- sistent with recent trends from other nomena of social and emotional delay tain Youth Clinics (Thornton). Connect- countries, such as Denmark, Sweden, in achieving adulthood.4,33 Longitudinal icut: Mauks Koepke Medical LLC Great Britain, Italy, and China.2,8,29–33 tracking is needed to clarify any impact (Danbury). Delaware: Pediatric Associ- For example, urban Han Chinese boys of overweight/obesity on boys’ sexual ates (Newark), Pediatric Practice Pro- achieve a testicular volume of $4mL development. The secular decrease we gram Christiana Care Health System (13% by age 9) and spermarche earlier observed in ages of onset of secondary (Wilmington), East Military: Naval Med- than studies conducted several deca- sexual characteristics in US boys ical Center–Portsmouth (Chesapeake). des ago; Danish boys achieve a testic- requires further study. Florida: Altamonte Pediatric Associates

PEDIATRICS Volume 130, Number 5, November 2012 e1065 Downloaded from www.aappublications.org/news by guest on September 26, 2021 (Altamonte Springs), Beaches Family Medical Clinic (Stevensville). Minnesota: town Pediatric Center PA (George- Health Center (Jacksonville), Eastside Brainerd Medical Center PA (Brainerd). town), MUSC Pediatric Primary Care Family Practice Center (Jacksonville), Missouri: Priority Care Pediatrics LLC (Charleston). Texas: Building Blocks Pe- Family Health Center–East and Oviedo (Kansas City), Tenney Pediatric and Ad- diatrics (Pleasanton), Child Care Asso- Children’s Health Center (Orlando), olescent LLC (Kansas City). North Caro- ciates (San Antonio), Laredo Pediatrics Orlando Regional Healthcare (Orlando), lina: Carolinas Medical Center Teen and Neonatology PA (Laredo), Practice Practice of Joseph Scarano, MD (Bra- Health Connection (Charlotte), Golds- of Sarah L. Helfand MD (Dallas), Texas denton), Practice of Mirtha E. Cuevas boro Pediatrics PA (Goldsboro). North Children’s Hospital (Houston), Texas MD Inc (Orlando), Santa Rosa Pediatrics Dakota: Altru Clinic (Grand Forks). Tech Pediatric Clinic (Odessa), Winns- of Florida (Milton), WestConnect Family Nebraska: Children’s Physicians (Omaha). boro Pediatrics (Winnsboro). Utah: Health Center (Jacksonville). Georgia: New Jersey: Delaware Valley Pediatric Practice of Joseph M. Johnson MD The Pediatric Center (Stone Mountain). Associates PA (Lawrenceville). New Mex- (Provo), Salt Lake Clinic (Sandy), Uni- Hawaii: Children’s Medical Association ico: Ben Archer Health Center (Truth or versity of Utah Health Sciences Center Inc (Aiea), Island Youth Heart and Consequences), Presbyterian Family (Salt Lake City), University South Main Health Center (Hilo), Practice of Chris- Healthcare–Rio Bravo (Albuquerque), Public Health Center (Salt Lake City), tine S. Hara MD (Honolulu), Practice of University of New Mexico Hospital Utah Valley Pediatrics LC (American Jeffrey Lim MD Inc (Honolulu). Iowa: (Albuquerque). Nevada: Sparks Pediat- Fork). Virginia: Alexandria Lake Ridge University of Iowa (Iowa City). Idaho: ric and Adolescent Medicine (Sparks). Pediatrics (Alexandria), Chesapeake Saint Alphonsus Medical Group Pediat- New York-1: Outer East Side Health Medical Group (Kilmarnock), Eastern rics (Caldwell). Illinois: Practice of Clinic (Buffalo), Saint Peters Health Virginia Medical School (Norfolk), River- Mary E. Lewis MD PC (La Grange), SW Center for Children (Albany); New side Pediatric Center (Newport News), Pediatrics (Orland Park). Indiana: Jef- York-2: Maimonides Infants and Child- Van Dorn Pediatrics and Adolescent fersonville Pediatrics (Jeffersonville), ren’s Hospital (Brooklyn), Practice of Medicine (Alexandria). Vermont: Hagan JMS Primary Care Center (Indianapo- Luis O. Herrera MD PC (Freeport), Prac- and Rinehart Pediatricians (South Bur- lis). Kansas: Ashley Clinic (Chanute), tice of R. Karim MD & L. Ganesh MD lington), University Pediatrics (Williston), University of Kansas School of Medicine (Rego Park), RidgewoodMedicalandDen- University Pediatrics–UHC Campus (Bur- ’ (Wichita). Louisiana: Ochsner Childrens tal (Brooklyn); New York-3: Bronx Leba- lington). Washington: Central Wash- – Health Center (New Orleans). Massa- non Pediatric Clinic Third Avenue ington Family Medicine (Yakima). chusetts: Baystate Pediatric Associates (Bronx), Haverstraw Pediatrics LLP Wisconsin: Beloit Clinic SC (Beloit), Co- fi fi (Spring eld), Baystate Pediatric Group (Haverstraw), Monte ore Medical Cen- lumbia–Saint Mary’s Germantown fi – (Spring eld), Burlington Pediatrics ter (Bronx), Pediatric Practice Bronx Clinic (Germantown), Gundersen Lu- (Burlington), Holyoke Pediatric Associ- Lebanon Hospital (Bronx), Practice of theran Medical Center (La Crosse), ates (Holyoke), Quabbins Pediatrics Julissa Baez MD PC (Bronx), Sound Waukesha Pediatric Associates (Waukesha). (Ware), University of Massachusetts Shore Medical Center (New Rochelle), Memorial Pediatrics and Internal Med- Union Community Health Center (Bronx). National Medical Association Pediatric icine (Westburough), University of Mas- Ohio: Children’s Choice Pediatrics (Stow), Research Network Practices (listed sachusetts Memorial Pediatric Primary Ohio Pediatrics (Kettering), Pediatric here by state): Florida: Practice of Care (Worcester), Wareham Pediatrics Associates of Lancaster (Lancaster), Arlene E. Haywood MD (Plantation). Ten- Associates (Wareham), Worcester Pedi- Professional Pediatrics Inc (Hilliard), nessee:MeharryMedicalCollege(Nash- atric Associates (Worcester). Maryland: The Cleveland Clinic Wooster (Woos- ville),PracticeofWillieMaeHubbardMD Cambridge Pediatrics LLC (Waldorf), ter). Oklahoma: Northwest Pediatrics (Chattanooga). Potomac Pediatrics (Rockville), Practice (Enid), Shawnee Medical Center Clinic Academic Pediatric Association’s Conti- of Steven E. Caplan MD PA (Baltimore), (Shawnee). Oregon: OHSU Doernbecher nuity Research Network Practices Shady Side Medical Associates (Shady Pediatrics–Westside (Portland). Pennsyl- (listed here by state): Florida: Carmen Side), Waldorf Pediatrics (Waldorf). vania: Saint Chris Care at Northeast Alfaro, MD; University of South Florida Maine: Kennebec Pediatrics (Augusta), Pediatrics (Philadelphia), Shaikh Pediat- (Tampa). Maryland: Maureen Parrott, Maine Coast Memorial Hospital (Ells- rics PC (Tobyhanna). Quebec: Clinique MD; Susan Feigelman, MD; University worth). Michigan: Children’sHospitalof Enfant-Medic (Dollard des Ormeaux). of Maryland School of Medicine (Balti- Michigan (Detroit), DeVos Children’sHos- Rhode Island: Northstar Pediatrics (Prov- more). Michigan: William Stratbucker, pital (Grand Rapids), Hurley Children’s idence), Practice of Marvin Wasser MD MD, MS; Devos Children’s Center (Grand Attending Clinic (Flint), Southwestern (Cranston). South Carolina: George- Rapids). New York: Daniel Neuspiel, MD;

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Beth Israel Medical Center (New York); the boys’ manual; Marsha L. Davenport, for photography work. We also ac- Maureen Parrott, MD; Pamela Jacobs, MD, who provided photographs for the knowledge Paul Kaplowitz, MD, Reuben MD; Lynn Garfunkel, MD; Rochester use of the orchidometer; John Fuqua, Rohn, MD, John Fuqua, MD, and Susan General Pediatric Associates (Roches- MD, Marsha L. Davenport, MD, and Rose, MD, for their expert opinion on ter). Ohio: Susan Monk, MD; Maria Anita Azam, MD, who provided photo- aspects of the study and their review of Nanagas, MD; Dayton Children’s Medi- graphs for certain aspects of Tanner the manual. Finally, we thank The Gen- cal Center (Dayton). Texas: Michelle staging of boys; Stanley M. Coffman, entech Center for Clinical Research Barratt, MD, MPH; Kids Place, University Duke University Medical Center Medi- who provided the initial orchidometers of Texas (Houston). cal Illustrations, who provided draw- and Terry Brown, whose expert wood- We thank the following for their contri- ings; and the University of North working skills allowed for us to con- butions to the study manual; Carlos J. Carolina School of Medicine Depart- tinue providing orchidometers to Bourdony, MD, for his part in creating ment of Educational Media Services clinicians.

REFERENCES

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(Continued from first page) www.pediatrics.org/cgi/doi/10.1542/peds.2011-3291 doi:10.1542/peds.2011-3291 Accepted for publication Jul 30, 2012 Address correspondence to Marcia E. Herman-Giddens, PA, DrPH, Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 1450 Russell Chapel Road, Pittsboro, NC 27312. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2012 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: Dr Reiter has received payment for services from NovoNordisk and Abbott. NovoNordisk produces growth hormone and Abbott produces testosterone. Neither of these agents were involved with this observational study. The small number of children receiving treatments with hormonal products were excluded from analyses. The other authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: Dr Herman-Giddens, Ms Steffes, Ms Harris, Dr Slora, and Dr Wasserman indicated that they have received some salary support from an unrestricted research grant from Pfizer Inc. We are grateful for the support of the following funders: Pfizer Inc., The American Academy of Pediatrics, Genentech Center for Clinical Research and Education, Health Resources and Services Administration, Maternal and Child Health Bureau, The Georgia Health Foundation, and The AAP Research in Pediatric Practice Fund.

e1068 HERMAN-GIDDENS et al Downloaded from www.aappublications.org/news by guest on September 26, 2021 Secondary Sexual Characteristics in Boys: Data From the Pediatric Research in Office Settings Network Marcia E. Herman-Giddens, Jennifer Steffes, Donna Harris, Eric Slora, Michael Hussey, Steven A. Dowshen, Richard Wasserman, Janet R. Serwint, Lynn Smitherman and Edward O. Reiter Pediatrics 2012;130;e1058 DOI: 10.1542/peds.2011-3291 originally published online October 20, 2012;

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/130/5/e1058 References This article cites 37 articles, 10 of which you can access for free at: http://pediatrics.aappublications.org/content/130/5/e1058#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Endocrinology http://www.aappublications.org/cgi/collection/endocrinology_sub Puberty http://www.aappublications.org/cgi/collection/puberty_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on September 26, 2021 Secondary Sexual Characteristics in Boys: Data From the Pediatric Research in Office Settings Network Marcia E. Herman-Giddens, Jennifer Steffes, Donna Harris, Eric Slora, Michael Hussey, Steven A. Dowshen, Richard Wasserman, Janet R. Serwint, Lynn Smitherman and Edward O. Reiter Pediatrics 2012;130;e1058 DOI: 10.1542/peds.2011-3291 originally published online October 20, 2012;

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