A dose-response study of hormone replacement in young hypogonadal women: effects on intima media thickness and metabolism.
OBJECTIVE
Young hypogonadal women appear to have an increased risk of cardiovascular disease. We studied the influence of increasing doses of hormone replacement therapy (HRT) on markers of metabolism and vascular physiology.


METHODS
Nine-month sequential dose-ranging study.


METHODS
A total of 25 young hypogonadal women (Turner Syndrome, n = 14; 46,XX gonadal dysgenesis, n = 9), hypogonadotrophic hypogonadism (n = 2), mean age 31.9 years (range 18.5-42.2). All subjects sequentially received oral 17beta-oestradiol 1,2 and 4 mg daily in a cyclical formulation for 12 weeks each.


METHODS
Metabolic markers and vascular physiology measurements to assess intima media thickness (IMT); arterial stiffness: pulse wave velocity (PWV) and augmentation index (AIx); endothelial function: flow-mediated dilatation (FMD). Results Increasing doses of oestrogen resulted in a reduction in IMT (0.63 +/- 0.06 vs. 0.58 +/- 0.06 vs. 0.56 +/- 0.06 mm at 1 mg, 2 mg and 4 mg 17beta-oestradiol, respectively, P = 0.001).


RESULTS
were similar in women with Turner Syndrome and normal karyotype. High-density lipoprotein (HDL) cholesterol concentrations increased (1.9 +/- 0.4 vs. 2.0 +/- 0.5 vs. 2.2 +/- 0.4 mmol/l, P = 0.001) and plasma glucose (4.8 +/- 0.4 vs. 4.7 +/- 0.3 vs. 4.6 +/- 0.6 mmol/l, P = 0.038) decreased slightly with the increasing dose of HRT. There was no correlation between the changes in IMT and HDL. Increasing HRT dose had no significant impact on blood pressure, weight, other lipid parameters, insulin, C-reactive protein, interleukin-6 and fibrinogen concentrations or FMD, PWV and AIx.


CONCLUSIONS
Increasing doses of HRT result in a reduction in carotid IMT in young hypogonadal women, along with increased serum HDL and decreased plasma glucose. This study raises the possibility that exogenous oestrogen may be cardioprotective in young women, but this observation needs to be balanced against a prothrombotic effect which is predominant in postmenopausal women.
Ostberg
Julia E
JE
Department of Endocrinology, University College London Hospitals, London, UK.
Storry
Clare
C
Donald
Ann E
AE
Attar
M Javad Hosseinzadeh
MJ
Halcox
Julian P J
JP
Conway
Gerard S
GS
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000032:analysis; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D008076:Cholesterol, HDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010053:Ovary / Q000002:abnormalities*; D012039:Regional Blood Flow; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000187:drug effects; D014424:Turner Syndrome / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D014463:Ultrasonography; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation
D001786:Blood Glucose; D008076:Cholesterol, HDL; D004958:Estradiol