A clinical study comparing the effects of sequential hormone replacement therapy with oestradiol/dydrogesterone and conjugated equine oestrogen/norgestrel on lipids and symptoms. Objective: The objective of the study was to compare the effects of sequential 17β-oestradiol/dydrogesterone and conjugated equine oestrogens (CEE)/norgestrel on lipid parameters, climacteric symptoms, bleeding patterns and tolerability. Study design: This double-blind study was conducted in 193 peri- and post-menopausal women randomised to receive six, 28-day cycles of oral sequential oestradiol 1 mg/dydrogesterone 10 mg or CEE 0.625 mg/norgestrel 0.15 mg. The change from baseline in serum lipids and hot flushes was analysed using a two-way analysis of variance. Results: After 24 weeks there was a statistically significant increase in high-density lipoprotein (HDL) cholesterol in the oestradiol/dydrogesterone group and a significant reduction in the CEE/norgestrel group. The difference between the groups was significant (P=0.001). The number of hot flushes was reduced by 86% in both groups; this improvement was supported by the Greene Climacteric Symptom Scale score, the patients' opinion and quality of life assessments. The percentage of women experiencing cyclic bleeding was greater with CEE/norgestrel, as was the mean duration and severity of bleeding. Both treatments were well tolerated. Conclusion: Oestradiol/dydrogesterone and CEE/norgestrel were equally effective in treating climacteric symptoms, but oestradiol/dydrogesterone showed some advantages in terms of lipid profile and incidence of bleeding.