Effect of Dosage of 17ß-Estradiol on Uterine Growth in Turner Syndrome—A Randomized Controlled Clinical Pilot Trial

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 3; pp. e716 - e724
• Main Authors: Cleemann, Line, Holm, Kirsten, Fallentin, Eva, Møller, Nini, Kristensen, Bent, Skouby, Sven O, Leth-Esbensen, Per, Jeppesen, Eva M, Jensen, Andreas K, Gravholt, Claus H
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.03.2020
• Subjects: 17β-Estradiol; Ambulatory care; Body mass index; Clinical trials; Dosage; Estrogens; Genetic disorders; Hormone replacement therapy; Patients; Puberty; Turner's syndrome; Ultrasonic imaging; Ultrasound; Uterus; 17β-estradiol; oral; uterus; Turner syndrome; ultrasound
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgz061

Abstract Context Most Turner syndrome (TS) girls need exogenous estrogen treatment to induce puberty and normal uterine growth. After puberty, the optimal estrogen treatment protocol has not been determined. Objective To compare 2 doses of oral 17ß-estradiol on uterine size. Design A double-blind, 5-year randomized controlled clinical trial. Setting Ambulatory care. Participants Twenty young TS women (19.2 ± 2.5 years, range 16.0–24.9) participated. Sixteen patients completed the study. No patients withdrew due to adverse effects. Intervention The lower dose (LD) group took 2 mg 17ß-estradiol/d orally and placebo. The higher dose (HD) group took 4 mg 17ß-estradiol/d orally. Main Outcome Measure(s) Uterine volume evaluated by transabdominal ultrasound yearly. Results Uterine size increased significantly more in the HD group compared with the LD group (P = 0.038), with a gain in uterine volume within the first 3 years of treatment of 19.6 mL (95% confidence interval [CI] = 4.0-19.0) in the HD group compared with 11.5 mL (95% CI = 11.2-27.9) in the LD group. The difference in 3-year gain was 8.1 mL (95% CI = 0.7-15.9). At the last visit, there were no significant differences in uterine volume between the groups. Conclusion HD oral 17ß-estradiol induces a steeper increase in uterine volume within the first years of treatment compared with the LD. However, the uterine growth potential seems to be the same in most young TS women making the duration of treatment equally significant as estrogen dose, although a few TS women did not experience sufficient uterine growth on 2 mg of estradiol. ClinicalTrials.gov NCT00134745 Abbreviations: BMI, body mass index; BSA, body surface area; DHEAS, dihydroepiandrosteronesulfate; HD, higher dose; HRT, hormone replacement therapy; LD, lower dose; TS, Turner syndrome; US, ultrasound