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Effects of Acute High Dose and Chronic Low Dose Estrogen on Plasma Somatomedin-C and Growth in Patients with Turner’s Syndrome^*

Department of Pediatrics, University of Vermont College of Medicine Burlington, Vermont 05405

Address requests for reprints to: Kenneth C. Copeland, M.D., Department of Pediatrics, University of Vermont College of Medicine, Given Building, Burlington, Vermont 05405.

Previously reported data with regard to the effects of estrogen on plasma somatomedin-C (Sm-C) concentrations are contradictory. This study was designed to evaluate, in the same subjects with Turner’s syndrome, the effects of both acute high dose and chronic low dose estrogen treatment on plasma Sm-C concentrations. Eight girls with Turner’s syndrome, aged 10 8/12 to 14 9/12 yr, were admitted to the Clinical Research Center for 3 days. Each received an iv infusion of conjugated estrogens (1.25 or 2.5 mg) in 12 h. Plasma Sm-C and serum GH and estrone levels were measured before, during, and after the infusion. The mean serum concentrations in the girls who received 1.25 mg conjugated estrogen increased from less than 222 pmol/L to 1905 ± 240 (±SE), 825 ± 166, and 296 ± 74 pmol/L immediately after, 12 h after, and 24 h after completion of the infusion, respectively. Serum GH concentrations were undetectable (<1 µg/L) before, during, and after the infusion. The mean plasma Sm-C concentrations decreased significantly (P = 0.02) after the infusion was terminated, falling from a mean basal value of 1.3 ± 0.2 (±SE) to a nadir of 0.6 ± 0.1 U/mL 12 h after completion of the infusion.

The same girls then were treated with low dose (5 µg ethinyl estradiol) estrogen therapy for 9–14 months. Seven of the eight girls had an increase in growth rate. The mean growth rate increased from 2.0 ± 0.5 to 5.4 ± 0.8 and 3.8 ± 0.4 cm/yr from 3 to 6 (P < 0.05) and from 9 to 14 months of treatment, respectively. Individual variability was great, however, and two of the eight girls never grew at a rate faster than 4.0 cm/yr during therapy. No consistent alteration in bone age relative to chronological age was found, and the growth response was not predicted by the bone age at the beginning of treatment. Mean plasma Sm-C concentrations did not change.

These studies demonstrated a growth spurt in girls with Turner’s syndrome during chronic low dose estrogen therapy, which was not associated with any change in plasma Sm-C concentrations. Acute high dose iv estrogen infusion resulted in a significant decline in plasma Sm-C concentrations. These results support the concept that in girls with Turner’s syndrome the plasma Sm-C response to estrogen is influenced by multiple, as yet undefined, factors.

^* This work was supported by Basil O’Connor Starter Research Grant 5–487 and Clinical Research Grant 6–465 from the March of Dimes-Birth Defects Foundation, General Clinical Research Center Grants 109 and 1346, and NIH Grant HD-10204 (to the Center for the Study of Reproductive Biology).

Received October 30, 1987.

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