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 (Oe 1 ), oestradiol (Oe 2 ) and oestrone sulphate (Oe 1 S) 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 Oe 1 , Oe 2 and Oe 1 S were all found to be 40-70% lower in smokers compared with non-smokers when ERT was given orally (Oe 1 S, P<0·05; Oe 1 and Oe 2 , P<0·01 for both). Oe 2 given orally caused a higher Oe 1 S/Oe 2 ratio but also a higher Oe 1 /Oe 2 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 Oe 1 S 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 Oe 2 replacement.

Treatment with high-dose estrogen (diethylstilbestrol) significantly decreases plasma estrogen and androgen levels but does not influence in vivo aromatization in postmenopausal breast cancer patients

“…In contrast, no change in plasma androgen levels were recorded among the patients treated with oral or transdermal hormone replacement therapy in a previous study [22] (Table 3). Similarly, progesterone and 17␣-hydroxyprogesterone plasma (Table 2).…”

“…Noteworthy, plasma androgen levels were not decreased in patients receiving estrogen hormone replacement therapy (HRT) at regular doses [22], revealing the effects to be specific for high-dose estrogen treatment or to DES as opposed to lower doses of estradiol given as HRT ( Table 3).…”

“…Thus, plasma samples obtained prior to and during treatment from 14 patients participating in a previous study comparing the effects of estradiol 2 mg p.o. versus 50 g/24 h transdermally [22] were analyzed for androstenedione and testosterone levels as one part of this study.…”

Effects of hormone replacement therapy on plasma viscosity and Doppler variations in postmenopausal non-smokers and heavy smokers

“…The reduction or loss of therapeutic efficacy is caused mainly by the smokingrelated increase in hepatic clearance, which generates an increased metabolism with more rapid elimination of estradiol [8]. The activity of the cytochrome P450 enzyme system changes, increasing the production and clearance of estradiol metabolites as a result of a more marked C2 hydroxylation and C2 methylation [9].…”

“…In contrast, estradiol given by the transdermal route is passed directly into the circulation. Hence, there is no significant influence of cigarette smoking on estradiol bioavailability and the favorable effects of [8].…”