Clinical Endocrinology

A dose-response study of hormone replacement in young hypogonadal women: effects on intima media thickness and metabolism


Gerard Conway, Department of Endocrinology, University College London Hospitals, 250 Euston Road, London NW1 2PQ, UK. Tel.: +44 (0) 20 7380 9101; Fax: +44 (0) 20 7380 9201; E-mail:


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.

Design  Nine-month sequential dose-ranging study.

Patients  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 17β-oestradiol 1,2 and 4 mg daily in a cyclical formulation for 12 weeks each.

Measurements  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 17β-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.