Context: Inter-vertebral discs have an important function in acting as shock absorbers in the spine, thereby helping to reduce the risk of vertebral body compression fractures. Previous cross-sectional studies have shown that loss of estrogen following the menopause is associated with a reduction in disc height whereas treatment with hormone replacement therapy (HRT) helps to maintain disc height. Our preliminary findings from a prospective trial had confirmed this benefit of HRT Objective: We now report extended findings from a prospective randomised clinical trial of HRT. Patients and interventions: 355 healthy postmenopausal women aged (mean±SD) 55.4±4.8 years were randomised to HRT with estradiol 1 or 2 mg plus dydrogesterone or to placebo. Methods: DXA measurements (Lunar DPX) were obtained at baseline and following 2 years of treatment. Main outcome measure: Inter-vertebral disc height was measured in discs between D12 to L3 using the bone densitometer ruler. Results: Compared with baseline, treatment with HRT resulted in a significant increase in total disc height with 1 mg estradiol 0.16±0.65 cm, p=0.015 and with 2 mg 0.21±0.86 cm, p=0.006 whilst there was no significant increase with placebo 0.13±0.65 cm, p=0.096. Between-group differences were not statistically significant. Conclusions: These results are in keeping with previous cross-sectional findings of a beneficial effect of estrogen on inter-vertebral discs. This may be in part responsible for the anti-fracture efficacy of HRT on vertebral fractures.