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The Journal of Pediatrics July 1995
Pubeffal staging in boys Frank M, Biro, MD, Anne W, Lucky, MD, Gertrude A, Huster, MA, and John A, Morrison, PhD From the Divisions of Adolescent Medicine, Pediatric Dermatology, and Pediatric Cardiology, Children's Hospital Medical Center, Cincinnati, Ohio, and Dermatology Research Associates, Cincinnati, Ohio
To determine the earliest signs of pubertal maturation, we followed 515 boys, aged 10 to 15 years at intake, every 6 months for 3 years. Changes in age, height, weight, body mass index, and serum levels of sex steroid hormones were significantly related to pubertal stage (PS). The earliest clinical stage of pubertal maturation, designated PS2a, was represented by the absence of pubic hair and a testicular volume 3 cc or greater; 6 months later, further maturation had occurred in 82% of these boys. Inclusion of PS2a as the earliest stage of puberty may help allay concerns about boys with perceived delayed maturation, and may allow more precise definition of early puberty. (J PEDIATR1995;I 27:100-2)
Several pubertal rating systems have been proposed; the most widely used is that of Marshall and Tanner. 1 In an earlier report, we noted that 3% of adolescents with gynecomastia, an event associated with pubertal maturation, had no pubic hair (Tanner pubic hair Stage 1).2 This observation led to a series of analyses to establish a set of criteria, based on clinical examination of both pubic hair and testicular volume, to define more precisely the earliest sign of pubertal maturation i n boys. METHODS Subjects were recruited from public and parochial schools in the greater Cincinnati area, as part of a longitudinal study of lipid changes during puberty. Schools were selected to yield a target of 50 black and 50 white students from each of grades 5 through 9. The study was approved by the institutional review board of the University of Cincinnati School of Medicine. Informed consent was obtained from a parent or legal guardian. The subjects were examined every 6 months (plus or mi-
Supported in part by National Institutes of Health grant R01 HDHL 18281 (Dr. Morrison). Presented in part at the 17th Annual National Meeting of the Society for Adolescent Medicine, Atlanta, Ga., March 1990. Submitted for publication Nov. 23, 1994; accepted Feb. 7, 1995. Reprint requests: Frank M. Biro, MD, Division of Adolescent Medicine, Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati OH 45229. Copyright © 1995 by Mosby-Year Book, Inc. 0022-3476/95/$3.00 + 0 9/22/63977
nus 1 month) for six visits. Physical assessment included height, weight, pubertal maturation (which assessed pubic hair stage as defined by Tanner), 1 and determination of testicular volume of the larger testis by means of the Prader orchidometer. Examiners were male and were unaware of the results of previous examinations. Body mass index was calculated from weight divided by height squared. Blood was drawn on the morning after an overnight fast, and placed in a cooler. The serum was separated to be frozen at -20 ° C. Total and free testosterone, dehydroepiandrosterone sulfate, estradiol, and testosterone-estrogen ANOVA DHEA-S PS TEBG
Analysis of variance Dehydroepiandrosteronesulfate Pubertal stage Testosterone-estrogenbinding globulin
binding globulin levels were determined as previously described.2pubertal staging was defined by criteria suggested from two earlier studies 2, 3:PS1 was defined as the absence of pubic hair and a testicular volume of the larger testis less than 3 cc. PS2a was defined as lack of pubic hair with a testicular volume of 3 cc or greater. Subsequent pubertal stages were based solely on pubic hair staging: PS2b was Tanner pubic hair stage 2; PS3 was Tanner pubic hair stage 3; PS4 was Tanner pubic hair stage 4; and PS5 was Tanner pubic hair stage 5. All data were entered by two different individuals as separate SAS data sets (Statistical Analysis Systems, SAS Institute, Inc., Cary, N.C., and compared for accuracy of entry. For each of the maturation variables of interest (hormone concentrations, age, and anthropometric measures), a two-
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I. Mean values of age, height, weight, body mass index, and serum hormone levels by pubertal stage, in 515 boys followed every 6 months for 3 years; A N O V A , with Duncan post-hoc analysis, by pubertal stage
Table
Pubertal stage Variable
P$ I
Age (yr) 11.44" Height (cm) 144.2" Weight (kg) 38.18" Body mass index 1.81" (kg/m2) Testosterone: nmol/L (ng/dl) Black subjects 0.8 (23)* White subjects 0.6 (16)* Free testosterone: 11 (0.33)* pmol/L (ng/dl) Estradiol: pmol/L 29 (8)* (pg/dL) DHEA-S: gmol/L 2.71 (997)* (ng/dl) TEBG (nmol/L) 34.6
PS2a
PS2b
PS3
PS4
PS5
12.18" 149.8" 41.65" 1.84"
12.79" 154.6' 47.27* 1.95"
13.74" 162.3" 54.67* 2.06*
14.63" 169.9" 61.11" 2.10"
15.19" 173.3" 66.88* 2.22*
3.0 (86)* 2.9 (83)* 60 (1.74)*
4.9 (141)* 4.6 (132)* 114 (3.28)*
11.5 (331)* 9.7 (281)* 294 (8.49)*
13.4 (338)* 13.3 (383)* 413 (11.9)*
15.5 (449)* 14.6 (422)* 504 (14.5)*
44 (12)*
59 (16)*
110 (30)*
150 (41)*
173 (47)*
3.31 (1220)*
4.04 (1490)*
4.75 (1750)*
33.3
28.4*
21.5'
5.08 (1870)* 14.4"
5.89 (2170)* 10.7"
*Duncan post-hoc analysis significant at p <0.0l.
IIA. Tanner pubic hair stage and testicular volume at subsequent visits for boys at pubertal stage 2a (PH = 1; testicular volume ->3 cc) maturation at baseline: Follow-up at 6 months (N = 84)
Table
Testicular volume Pubic hair stage
I cc
2 cc
3 cc
4 cc
5 cc
6 cc
8 cc
PH1 PH2 PH3
1 (1) 0 0
6 (7) 0 0
8 (10) 4 (5) 0
15 (18) 9 (11) 2 (2)
8 (10) 3 (4) 1 (1)
9 (11) 8 (10) 1 (1)
7 (8) 1 (1) 1 (1)
Values are number (percentage) of subjects. PH, Pubic hair stage.
Table liB. Follow-up at 12 months (N = 75) Testicular volume Pubic hair stage
3 cc
4 cc
5 cc
6 cc
8 cc
->10 c c
PHI PH2 PH3 PH4
4 (5) 3 (4) 0 0
9 (12) 12 (16) 1 (1) 0
3 (4) 6 (8) 3 (4) 0
3 (4) 4 (5) 5 (7) 1 (1)
0 7 (9) 3 (4) 1 (1)
0 3 (4) 6 (8) 1 (1)
Values are number (percentage) of subjects. PH, Pubic hair stage.
way analysis of variance, with adjustment for variation because of subject, was used to test for the effect of (1) pubertal stage, (2) race, and (3) interaction of race by stage. If there was no significant interaction and the main effect of pubertal stage was significant at p <0.01, then a Duncan multiple range test at p = 0.01 was used to determine which stages
differed. If the analysis revealed a significant interaction (p <0.05) between race and stage, the effect of pubertal stage was evaluated separately for each race by means of a oneway repeated measures A N O V A , with adjustment for variation because of subject. Similarly, the effect of race was evaluated separately for each stage. Each of the models de-
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scribed above was computed by the SAS Proc GLM procedure. 4 When th e effect of pubertal stage on maturation variables was evaluated, all data from stages PS2a through PS4 were included in the data set. For any subject, only the initial visit in stage PS5 was analyzed for stage PS5, and only the last visit in stage PS 1 was analyzed for pubertal stage PS 1. RESULTS There were 539 boys, aged 10 to 15 years at intake, recruited into the study. Twenty-four boys were excluded from further analyses: 22 because they were in stage PS5 at the time of intake, and two because they were in stage PS 1 at the last visit of the study. The final sample consisted of 237 black and 278 white boys. Overall, 88.5% of participants were seen at all six visits, and an additional 3.9% were seen at five visits. Anthropometric and hormonal data were analyzed for significance of race, pubertal stage, and the interaction of race by stage. Results of all ANOVA were significant (p <0.0001) when the effect of pubertal stage on age, height, weight, and body mass index, as well as on the hormone variables testosterone, free testosterone, estradiol, DHEA-S, and TEBG, was examined (Table I). A race-by-stage interaction was observed only for total testosterone (Table I). The Duncan post hoc analysis revealed that each pubertal stage was significantly different (p <0.01) from all other stages for .-11 anthropometric and hormonal variables, with the exception of PSI and PS2a for TEBG (Table I). Most (175/184, 95%) subjects were noted, at the 6-month intervals, to enter puberty through testicular enlargement without pubic hair maturation (PS 1 to PS2a); nearly all of the remainder (7/9) had maturation of both pubic hair and testicular growth at entry to puberty. To confirm that PS2a represented a valid stage in pubertal development, we examined prepubertal subjects, who were noted at a later visit to enter PS2a, for their staging at subsequent visits. The majority (69/84) of subjects with no pubic hair and a testicular volume of 3 cc or greater had an advanced testicular volume (>-4 cc) or an advanced pubic hair stage (>-PH2), or both, when examined 6 months later (Tables IIA and liB). Additionally, all results of univariate analyses of anthropometric and hormonal variables were in a pubertal range when these subjects were seen at the next 6-month visit (data not shown). Stage PS2a had a mean duration of 0.61 year. DISCUSSION Pubertal maturation, rather than chronologic age, appears to be more important in studies of biologic and psychologic phenomena in teenagers. Examples include peak growth velocity,5 sex steroid hormone levels,6 hematocrit levels] electrocardiographic changes, s and acne. 9 Previous studies (such as that of Wilson et al. 1°) have used a number of pu-
The Journal of Pediatrics July 1995
bertal maturation systems, particularly when establishing an overall maturation "score" or "index." However, the Tanner gonadal staging has been reported as an unreliable sign of early pubertal maturation, s, 11 In a group of Swiss boys, testicular volume of 3 cc was found to be the most reliable indicator of the onset of puberty. 8 Similar to their findings, the majority (82%) of both black and white boys in this study with a testicular volume 3 cc or greater had a further increase in testicular volume or pubic hair stage, or both, when reexamined 6 months later. Additionally, the boys in PS2a had total and free testosterone levels that were in the pubertal range. As shown by this study, the use of pubic hair staging alone may lead to misclassification of some boys in the earliest segment of pubertal maturation (i.e., when there is testicular enlargement without pubic hair growth). Clinicians may consider obtaining endocrinologic studies because of lack of pubic hair, whereas careful palpation of the testes would have indicated the onset of puberty. Including an increase in testicular volume as the definition of the earliest stage of puberty, PS2a, may help allay the concerns of boys and their parents with perceived delayed maturation and, in addition, allow clinical investigators to define early puberty more precisely. We thank Loretta Simbartl, MS, for statistical consultation. REFERENCES 1. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970;45:13-23. 2. Biro FM, Lucky AW, Huster GA, Morrison JA. Hormonal studies and physical maturation in adolescent gynecomastia. J PEDIATR 1990;116:450-5. 3. Largo RH, Prader A. Pubertal development in Swiss boys. Helv Paediatr Acta 1983;38:211-28. 4. SAS users' guide: Basics. 5th ed. Cary, North Carolina: SAS Institute, 1985. 5. Buckler JMH. Skeletal age changes in puberty. Arch Dis Child 1984;59:115-9. 6. Halpern CT, Udry JR. Variation in adolescent hormone measures and implications for behavioral research. Journal of Research on Adolescence 1992;2:103-22. 7. Daniel WA. Hematocrit: maturity relationship in adolescence. Pediatrics 1973;52:388-94. 8. Stafford EM, Weir MR, Pearl W, Imai W, Schydlower M, Gregory G. Sexual maturity rating: a marker for effects of pubertal maturation on the adolescent electrocardiogram. Pediatrics 1989;83:565-9. 9. Lucky AW, Biro FM, Huster GA, Morrison JA, Elder N. Acne vulgaris in early adolescent boys. Arch Dermatol 1991; 127:210-6. 10. Wilson DM, Kraemer HC, Ritter PL, Hammer LD. Growth curves and adult height estimation for adolescents. Am J Dis Child 1987;141:565-70. 11. Taranger J, Engstrom I, Lichtenstein H, Svennberg-Redegren I. Somatic pubertal development. Acta Paediatr Scand 1976; 258:121S-35S.