Twenty-four hours secretion pattern of serum estradiol in healthy prepubertal and pubertal boys as determined by a validated ultra-sensitive extraction RIA

Abstract

Background: The role of estrogens in male physiology has become evident. However, clinically useful normative data for estradiol secretion in boys has not previously been established due to the insensitivity of current methods used in clinical routine. By use of a validated ultra-sensitive extraction RIA, our aim was to establish normative data from a group consisting of healthy boys in prepuberty and during pubertal development.

Methods: Sixty-two 24-hours serum profiles (6 samples/24 hours) were obtained from 44 healthy boys (ages; 7.2-18.6 years) during their pubertal development, classified into five stages: prepuberty (testis, 1-2 mL), early (testis, 3-6 mL), mid (testis, 8-12 mL), late-1 (testis,15-25 mL, not reached final height) and late-2 (testis,15-25 mL, reached final height). Serum estradiol was determined by an ultra- sensitive extraction radioimmunoassay with detection limit 4 pmol/L and functional sensitivity 6 pmol/L.

Results: Mean estradiol concentrations during 24-hours secretion increased from prepuberty (median: <4 (5-95 percentiles: <4 - 7) pmol/L) to early puberty (6 (<4 - 12 pmol/L) but then remained relatively constant until a marked increase between mid-puberty (8 (4 - 17) pmol/L) and late-1 (21 (12 - 37) pmol/L) puberty, followed by a slower increase until late-2 puberty (32 (20 - 47) pmol/L). The diurnal rhythm of serum estradiol was non-measurable in pre- and early puberty, but discerned in mid-puberty, and become evident in late pubertal stages with peak values at 0600 to 1000 h.

Conclusion: With the use of an ultra-sensitive extraction RIA, we have provided clinically useful normative data for estradiol secretion in boys.

Figure 1

Mean estradiol concentration during 24-hours secretion. Concentrations below the detection limit (patterned area) during 24-hour sampling were set to the expected value of 2 pmol/L. A. Mean estradiol during 24 hours from 62 serum profiles. The bars show the median for the estradiol level in each pubertal group. B. Mean estradiol during 24 hours serum profiles in samples from 8 boys who have been followed-up with repeated estradiol measurements during pubertal development.

Figure 2

Twenty-four hours secretion pattern of serum estradiol in healthy pubertal boys. Upper panel: Individual 24-hour serum profiles of estradiol in 30 healthy boys. The patterned areas indicate values below the analytical detection limit. Lower panel: Normative data for the 24-hours secretion of serum estradiol. Shaded areas show 5–95 percentiles for each pubertal stage. Data is based on 17 boys in early puberty with testicular volume 3–6 mL (A), 10 boys in mid-puberty with testicular volume 8–12 mL (B), 10 boys in late-1 puberty, with testicular volume 15–25 mL, -1 to +2 years from peak height velocity (PHV), who have not reached final height (C) and 9 boys in late-2 puberty, with testicular volume 15–25 mL, +2 to +3 years from PHV and who have reached final height (D).

Figure 3

Diurnal rhythm of serum estradiol during pubertal development in healthy boys. For each study subject, the percentage difference from the mean value/24 h was calculated every four hours before dividing into pubertal groups. Data are shown as the mean value ± standard error of the mean for each pubertal group and clock time. Data is based on 17 boys in early puberty with testicular volume 3–6 mL, 10 boys in mid-puberty with testicular volume 8–12 mL, 10 boys in late puberty, with testicular volume 15–25 mL who have not reached final height and 9 boys in late puberty, with testicular volume 15–25 mL who have reached final height.

Figure 4

Mean concentration during 24 hours of serum estradiol, testosterone and DHEAS in relation to chronological age and bone age (TW2) in healthy boys. Estradiol and testosterone values below the detection limits are set to the expected values of 2 pmol/L and 0.02 nmol/L, respectively, before calculation of mean value.

Figure 5

Linear regression analysis between serum testosterone and serum estradiol during 24-hours sampling at different pubertal stages in healthy boys. Boys followed up by repeated measurements were randomized to participate once in the analyses. Serum estradiol correlated significantly with serum testosterone: r = 0.38, p < 0.001 and r = 0.58, p < 0.001 for early to mid-puberty and late puberty, respectively. Estradiol values below the detection limit are set to the expected value of 2 pmol/L.