A randomised comparison of the effects of oral versus transdermal 17beta-oestradiol, each combined with sequential oral norethisterone acetate, on serum lipoprotein levels.

OBJECTIVE: To investigate the effects of oral versus transdermal 17beta-oestradiol, given in both cases with sequential addition of oral norethisterone acetate, on serum lipid and lipoprotein levels in postmenopausal women. DESIGN: Open, randomised, parallel groups study. SETTING: University Clinical Research Group. POPULATION: Sixty-four postmenopausal women with climacteric complaints who were otherwise healthy were screened. Of these, 58 fulfilled the entry criteria. METHODS: Fifty-eight postmenopausal women were randomised to receive either oral 17beta-oestradiol/oestriol (Trisequens) or transdermal 17beta-oestradiol (Estrapak) together with cyclical addition of norethisterone acetate for 48 weeks. MAIN OUTCOME MEASURES: Serum levels of total cholesterol, triglycerides, high density lipoproteins (HDL), low density lipoproteins (LDL), very low density lipoproteins (VLDL), apolipoproteins, and lipoprotein(a) at baseline, and after 46 weeks (oestrogen-alone phase), and 48 weeks (oestrogen-progestogen phase) of treatment. RESULTS: Oral oestradiol therapy did not affect serum total cholesterol levels during the oestrogen-alone phase, but during the combined phase there was a 5% fall (P < 0.05) due to a 7% decrease in LDL cholesterol levels (P < 0.01). Oral therapy also increased serum triglyceride levels by 9.4% during the oestrogen-alone phase (P < 0.05). During the combined phase of transdermal therapy, there was a 19% fall in serum triglyceride levels (P < 0.05) and a 6% fall in HDL levels (P < 0.05). Oral oestradiol reduced lipoprotein(a) levels by 31% during the oestrogen-alone phase and by 37% with norethisterone acetate addition (P < 0.05). Transdermal therapy had no significant effect on lipoprotein(a). CONCLUSIONS: Other than a minor fall in HDL3 in women receiving transdermal 17beta-oestradiol, coadministration of oral progestogen in general improved, rather than worsened, this serum lipoprotein profile.