Hormone Replacement Therapy to Treat Turner Syndrome

Turner Syndrome (TS) is characterized by ovarian dysgenesis and short stature resulting from the partial or complete deletion of one X-chromosome. Adults with TS have excessive rates of osteoporosis, hypertension, dyslipidemia and diabetes mellitus and may have increased morbidity and mortality as a result. These problems of adults with TS may be secondary to deficiency of ovarian hormones or may result from halpo-insufficiency for as yet unknown X-chromosome genes. There have been no prospective, controlled studies of the effects of hormone replacement therapy (HRT) in TS, but available data suggest that conventional oral HRT designed for postmenopausal women may not prevent osteoporosis and may aggravate hypertension in this disorder. Of note, girls and women with TS are deficient in ovarian androgens as well as estrogen, and have reduced muscle mass, which may contribute to osteoporosis and insulin resistance. In addition, reduced androgens may contribute to the impairment of self esteem and social interactions suffered by many with TS. In this study, two different hormone regimens for TS will be compared in a randomized, placebo-controlled, double-blind design. Both groups will receive transdermal estradiol (E2, 100 mcg/day) with cyclic progesterone; one group will receive a physiological dose of testosterone (T) by transdermal patch while the other group will receive a placebo patch. The treatment duration is 2 years. Major outcome parameters include predicted improvements in bone mineral density, body composition and psychosocial well-being. Essential information will be collected on the effects of hormone treatments on insulin sensitivity and blood pressure in TS. This study will help to optimize hormone replacement treatment for women with TS, and to clarify which of the metabolic problems of TS are secondary to ovarian hormone deficiency, and which are due to genetic factors.