Short Term, Low Dose Estradiol Accelerates Ulnar Growth in Boys*

Abstract

We previously described a biphasic dose-response curve for ethinyl estradiol on short term growth in patients with Turner's syndrome. To investigate whether there is a similar phenomenon in boys, we measured the 3-week ulnar growth velocity (TUG) after administration of different doses of estradiol to five prepubertal or early pubertal boys. Basal TUG was determined initially. Subsequently, the boys received a 4-day iv infusion of estradiol at each of three doses (4, 20, and 90 micrograms/day) given double blind in a randomized sequence. TUG was determined before and after each infusion and was allowed to return to baseline before giving the second and third infusions. Mean TUG increased from 0.45 +/- 0.11 (+/- SEM) to 1.38 +/- 0.51 mm/3 weeks after the 4 micrograms/day infusion (P less than 0.05), from 0.49 +/- 0.11 to 1.0 +/- 0.4 mm/3 weeks after the 20 micrograms/day infusion (P = NS), and from 0.46 +/- 0.1 to 0.84 +/- 0.12 mm/3 weeks after the 90 micrograms/day infusion (P = NS). The mean serum estradiol level was 10 +/- 2.3 pg/ml during the 4 micrograms/day infusion, 16 +/- 2.3 pg/ml during the 20 micrograms/day infusion, and 96 +/- 12 pg/ml during the 90 micrograms/day infusion. Mean serum somatomedin-C levels were significantly higher only after the 20 and 90 micrograms/day estradiol infusions. We conclude that low dose estrogen can stimulate ulnar growth in boys and may play a role in the male pubertal growth spurt.

Estrogen levels in childhood determined by an ultrasensitive recombinant cell bioassay.

“…Androgens are unlikely to be the cause of this growth spurt, since the onset of the growth spurt in boys is much later than in girls, despite their having equal or higher levels of androgen. Consistent with this view, the infusion of estradiol at the dose of 4 ,ug/d causes a tripling of ulnar growth rate in boys (3). The plasma estradiol level corresponding to this dose is -4 pg/ml based on extrapolation from the levels at higher dose infusions.…”

Vertebral morphology in aromatase inhibitor–treated males with idiopathic short stature or constitutional delay of puberty

“…The AM:MP ratios, which were of 1.0 of less in all deformed vertebral bodies, suggest that disturbed growth is more likely, although the index has been validated only in adults. (15) Estrogen is a wellknown regulator of endochondral bone growth and is critical for bone maturation and epiphyseal fusion, (1)(2)(3)(4)(5)16) but it is not known whether estrogen (or estrogen deprivation) influences endochondral bone growth and maturation similarly in the axial and appendicular skeleton. In juvenile rabbits and mice, estrogen treatment reduces chondrocyte proliferation and growth plate height, whereas letrozole may decrease the differentiation rate of growth plate chondrocytes and increase growth plate height.…”

The role of estrogen receptor-α and its activation function-1 for growth plate closure in female mice

“…Low E 2 levels enhance skeletal growth during early sexual maturation (i.e., the pubertal growth spurt), whereas high E 2 levels during late puberty result in growth plate fusion and thereby cessation of longitudinal bone growth in humans and reduced longitudinal bone growth in rodents (4,5,10,14). The mechanisms of action for these two seemingly opposite effects of estrogens on longitudinal bone growth are not fully understood but clearly depend on maturational stage and serum levels of E 2 (2,4,10,14).…”