Clinical Trial: Initiating Transdermal Estradiol Therapy in Turner's Syndrome
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
Official Title: Initiating Transdermal Estradiol Therapy in Turner's Syndrome
Brief Summary:
This is a multicenter, randomized, controlled, semi-blinded study to compare two low doses of estradiol administered by recently available transdermal patches for the initiation of puberty in Turner syndrome girls 11.5-13.0 years old in conjunction with growth hormone (GH) therapy.
The specific hypotheses to be tested are: when combined with growth hormone (GH) treatment, low dose transdermal estradiol (LTE2) replacement will be more effective in stimulating feminization, height velocity, and bone mineral density without compromising growth potential than very low dose transdermal estradiol (VLTE2), which will in turn be superior to GH alone in effects on feminization, height velocity, and bone mineral density.
Detailed Summary:
Determining the estrogen replacement regimen which is optimal with GH therapy is an important issue in the management of Turner syndrome today. The estrogen effect on growth is biphasic, stimulatory at low doses but inhibitory at higher doses (1). In addition, the form, route, and timing of estrogen seem to be important determinants of estrogen effects on growth (2). Pubertal estrogen replacement treatment is customarily delayed until about 15 years of age in the USA to give GH treatment more time to act because standard estrogen treatment inhibits growth (3), in part by direct effects on epiphyseal senescence and fusion (4, 5) and in part by acting as a GH antagonist (6).
Our pilot studies suggest that the form and route of estrogen are important determinants of estrogen effects on growth (2, 7). We recently found that very low doses of parenteral (IM depot) estradiol (E2) together with recombinant growth hormone (GH) to Turner syndrome patients as young as 12-12.9 years of age produced a significantly greater adult height than standard doses of oral conjugated estrogen at this age (7). Thus, very low doses of the natural estrogen (estradiol, E2) administered into the systemic circulation seem optimal for growth stimulation.
Very little data are available about the optimal E2 dose for stimulation of epiphyseal growth and how this may relate to the optimal dosage for accrual of bone mineral density and feminization.
Our recent pilot study started with a depot E2 dose of 0.2 mg; the monthly dose was then increased by 0.2 mg at successive 6-month intervals. The lowest dose (0.2 mg) stimulated height velocity the most. However, it did not stimulate breast development as reliably as the larger doses (≥ 0.4 mg monthly), which were also growth stimulatory although to a less
Sponsor: University of Chicago
Current Primary Outcome: The net change of height velocity between Group 2 and Group 3 and the net change in predicted height between Group 2 and Group 3. [ Time Frame: 12 months ]
Original Primary Outcome: Same as current
Current Secondary Outcome: Plasma E2 level to document the dose-response effect of the applied prescription and uterine dimensions to quantitate the estrogenic effect on growth and development of the uterus. [ Time Frame: 12 months ]
Original Secondary Outcome: Same as current
Information By: University of Chicago
Dates:
Date Received: March 5, 2009
Date Started: April 2009
Date Completion:
Last Updated: March 10, 2014
Last Verified: March 2014
