Effect of Biosynthetic Growth Hormone and/or Ethinyl Estradiol on Adult Height in Patients With Turner Syndrome
Effect of Biosynthetic Growth Hormone and/or Ethinyl Estradiol on Adult Height in Patients With Turner Syndrome
Turners Syndrome is a genetic condition in females that is a result of abnormal chromosomes.
 Girls with Turner syndrome are very short as children and as adults. Although their growth
 hormone secretion is almost always normal, giving injections of growth hormone to Turner
 syndrome girls may increase their rate of growth. In addition, most girls with Turner
 syndrome do not have normal ovaries.

 In normal girls the ovaries begin producing small amounts of the female sex hormone, estrogen
 at about 11 - 12 years of age. As girls grow older the level of estrogen increases. Estrogen
 is responsible for the changes in girls known as feminization. During feminization the hips
 grow wider, the breasts develop, there is an increase in the rate of growth, and eventually
 girls experience their first menstrual period.

 This study was designed to evaluate the effect of low dose estrogen, growth hormone, and the
 combination of low dose estrogen and growth hormone on adult height in girls with Turner
 syndrome. Patients will be entered into the study from ages 5 to 12 and will be randomly
 placed into one of four groups.

 1. Group one will receive low dose estrogen

 2. Group two will receive growth hormone

 3. Group three will receive both low dose estrogen and growth hormone

 4. Group four will receive a placebo "sugar pill"

 Once started, the treatment will continue until the patients approach their adult height, and
 growth slows to less than 1/2 inch over the preceding year. This usually occurs by the age of
 15 or 16.

 Patients will be seen at the outpatient clinic every 6 months during the study and will
 receive a routine check-up with blood and urine tests, and hand/wrist X-rays to determine
 bone age. On patient's yearly visits they will have the density of bone measured in their
 spine and forearm.
Adult women with Turner's syndrome are quite short. Several treatments have been used to
 increase growth rate in these patients. They include oxandrolone (1), growth hormone (2, 3),
 and low dose estrogen (4). However, the ability of these hormone treatments to increase adult
 height has never been evaluated in controlled clinical trials.

 We propose to evaluate the effect on adult height of low dose estrogen, growth hormone, and
 the combination of low dose estrogen and growth hormone. Patients will be entered into the
 study from ages 5 to 12 and will be assigned randomly to one of the four groups (the 3 above
 treatment groups or placebo). The randomized assignment will be double-blind throughout the
 study. Treatment will be maintained to adult height (the first height measurement at which
 the preceding annual growth rate was < 1.5 cm). Beginning at age 12, the estrogen treatment
 in all 4 groups will be changed to a standardized regimen of increasing estrogen dose, so
 that all children in the study will undergo secondary sexual changes at an appropriate age.

 In addition, the study will assess the effect of growth hormone and estrogen treatment on
 bone density and, in a parallel, separate, study, the effect of treatment on cognition and
 learning ability.
INCLUSION CRITERIA

 All subjects will be outpatients.

 Patients must be females with Turner's syndrome diagnosed by leukocyte karyotype

 Chronologic age greater than or equal to 5 years.

 Prepubertal Tanner I status. If breast development is Tanner II or III, demonstration of
 castrate status through measurement of serum FSH (greater than 12 MIU/ML).

 All patients must be below the 10th percentile for chronologic age.

 Patients must have at least 6 months accurate, growth measurements available for
 calculation of pre-study growth velocity. Pretreatment measurements must be obtained during
 a time when the patient is not receiving a potential growth-promoting agent.

 Patients judged to be thyroxine deficient must have replacement which has resulted in
 normal thyroid function tests over the three-month period prior to enrollment (T4, T3,
 Thyroid Stimulating Hormone).

 Patients and/or parents or legal guardians of patients must sign an informed consent
 statement. Assent should be obtained from all patients competent to understand the
 protocol. Local IRB requirements apply.

 EXCLUSION CRITERIA

 Patients who have received any form of human growth hormone within the past 3 months, or
 who have received a cumulative course of therapy totaling greater than one year.

 Patients who have received treatment with estrogen or androgen in the past three months or
 who have received a cumulative course of therapy totaling greater than one year.

 Patients who have any Y component in their chromosome analysis.

 Patients with a chronologic age greater than 12 years.

 Patients with a bone age greater than 12 years.

 Patients who have clinically significant cardiac, pulmonary, gastrointestinal, hepatic or
 renal disease or who have had any malignancy.

 Patients who have significant hematuria or proteinuria in pretherapy evaluation.

 Patients who have diabetes mellitus.

 Patients who have any active chronic infection (tuberculosis).

 Patients who are taking amphetamines or any other drugs known to interfere with growth
 hormone secretion or actions.

 Patients who are poor medical, psychological, or psychiatric risks for whom, in the opinion
 of the principal investigator, the investigational drug would be unwise.

 Patients whose parents are substance abusers, nor those who come from homes in which
 appropriate emotional development may be limited.

 Patients who cannot be seen on the schedule required by the protocol.