Plasma oestrogen fractions in postmenopausal women receiving hormone replacement therapy: Influence of route of administration and cigarette smoking

Abstract

The aim of this study was to determine the impact of the administration route and cigarette smoking on plasma oestrogen levels during oral and parenteral oestrogen replacement therapy (ERT). Fourteen healthy postmenopausal women (six smokers and eight non-smokers) were recruited for a prospective, randomised, crossover study at a private outpatient medical centre in Oslo, Norway. All patients were randomised to receive cyclic therapy with oestradiol and norethisterone orally or by the transdermal route each for a 6-month period. Plasma levels of oestrone (Oe1), oestradiol (Oe2) and oestrone sulphate (Oe1S) were determined using highly sensitive RIA methods before and during hormone replacement therapy given by the oral and transdermal route. Comparing smokers and nonsmokers, plasma levels of Oe1, Oe2 and Oe1S were all found to be 40-70% lower in smokers compared with non-smokers when ERT was given orally (Oe1S, P<0.05; Oe1 and Oe2, P<0.01 for both). Oe2 given orally caused a higher Oe1S/Oe2 ratio but also a higher Oe1/Oe2 ratio compared with parenteral therapy in smokers (40.2 versus 7.0, P<0.01; and 3.2 versus 0.8, P<0.05 respectively). No significant differences in these parameters in the different test-situations were seen in non-smokers. Except for a lower level of Oe1S in smokers (non-significant), no difference in plasma oestrogen levels between smokers and non-smokers was observed during parenteral therapy. In conclusion, cigarette smoking has been shown to have major impact on plasma oestrogen levels during oral but not during parenteral Oe2 replacement.