Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism

Status:	Archived
Conditions:	Other Indications, Women's Studies, Endocrine
Therapuetic Areas:	Endocrinology, Other, Reproductive
Healthy:	No
Age Range:	Any
Updated:	7/1/2011
Start Date:	January 2009
End Date:	December 2011

Estrogen Dosing in Turner Syndrome:Pharmacology & Metabolism

Estrogen is necessary for feminization during puberty and to decrease bone resorption, the
latter critical for the achievement of peak bone mass and normal bone health in the female.
The practicing pediatric endocrinologist often faces the dilemma of how to best feminize
girls with hypogonadism (lack of estrogen), manifested as delayed or arrested puberty, due
to disorders of the brain or the ovaries. We propose a series of studies to address which
type, dose, and route of delivery of estrogen are suitable choices in feminizing and
sustaining estrogen concentrations in adolescent girls with Turner syndrome. To accomplish
this we will study girls/young woman between the ages of 13 to 20 with Turner Syndrome in 2
protocols. In Protocol # 1 we will study 24 girls with TS, they will receive 3 different
estrogen preparations, either by mouth or via a patch for a total of 6 weeks. They will
come to the clinical research center for blood draws after 2 wks of taking the estrogen.
With this study, we hope to learn how the body responds to estrogen differently, depending
on the form estrogen is given and how high, estrogen levels gets in the blood in these girls
with Turner Syndrome. We will be comparing these patients estrogen levels to girls that
menstruate normally and do not have Turner Syndrome. In Protocol #2, 40 patients with TS
will be recruited; these patients will take estrogen for 1 year, either by mouth or via a
patch. Patients will come to the lab for blood drawn in 7 occasions and we will measure
estrogen levels as well as other hormones and lipid levels. We will also perform a DEXA
study (like an X ray) to assess body composition and bone mineralization. We will adjust
doses based on the estrogen levels we find. With this study we hope to learn how estrogen
affects body composition, i.e., the amount of fat vs. muscle, and how different forms of
estrogen affect blood cholesterol and other hormones. This study will allow us to understand
better how to best replace young woman with Turner Syndrome with estrogen.

Data on the specific effects and bioequivalency of the different forms of estrogen are
lacking, and in the young adolescent age group in particular, virtually non-existent. This
has been complicated further by the difficulty in accurately interpreting estradiol assay
results as the conventional radioimmunoassays (RIA) for estradiol are inaccurate and
insensitive measuring very small concentrations in plasma. There is wide variation in the
types of estrogens used for estrogen replacement, as well as doses and route of
administration. Girls with Turner syndrome (TS) represent an important case study for these
issues as they have early primary gonadal insufficiency or failure many years before the
achievement of peak bone mass. Hence, a study of the effects of different estrogen compounds
in this patient population offers a unique model that eliminates the confounding effects of
other products produced by the intact gonad. Since in this condition it is imperative that
estrogen replacement is started during the adolescent years and continued for several
decades, this issue becomes highly relevant to these young women's health.Our specific aims
are to: 1. to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) and relative
biological potency of different oral vs. transdermal preparations of estradiol using
state-of-the-art tandem mass spectrometry assays and recombinant cell bioassays; 2. to
investigate the differential, long term metabolic effects of oral vs. transdermal estrogen
replacement, specifically the effects on lipid and protein metabolism as well as body
composition in this patient population; 3. to determine feasibility of estrogen
concentration-based dosing in puberty and 4. To characterize the metabolic profile of TS
girls previously treated with GH. To accomplish this we will study girls/young woman between
ages 13 to 20 with TS in 2 protocols. Protocol #1 will be a study of the PK/PD of 3
different preparations of estrogen in different doses. Protocol #2 will be a one year
longitudinal study of the effects of oral vs. TD estrogen on body composition, hormones and
growth factors.

We found this trial at

sites

Nemours Children's Clinic

807 Childrens Way
Jacksonville, Florida 32207

(904) 697-3600