Acute and long-term estradiol kinetics in smoking postmenopausal women

ABSTRACT

Aim We aimed to study 2-h estrogen kinetics in smoking versus non-smoking postmenopausal women receiving estrogen therapy. Moreover, we wished to study estrogen concentrations over 2 years in smokers using ten or fewer cigarettes daily versus non-smokers in postmenopausal women on estrogen treatment.

Method We used post-hoc analyses from two randomized trials. In study I, we included 150 women from three groups receiving therapies containing 1 or 2 mg 17β-estradiol, where trough and 2-h blood samples was collected in cycles 1, 7 and 13. In study II, we included 94 completing women who had received either placebo or a regimen containing 1 mg 17β-estradiol.

Results In study I, 35% were smokers. At 2 h post tablet intake, serum estrone and estradiol concentrations were significantly lower in smokers as compared to non-smokers, i.e. mean serum estrone was 212 pg/ml (95% confidence interval (CI) 177–247 pg/ml) in smokers as opposed to 318 pg/ml (95% CI 278–359 pg/ml) in non-smokers on 1 mg estradiol (p = 0.0002). In study II, 19% were smokers. In the estrogen group, smoking lead to significantly lower levels of both serum estrone and serum estradiol at all post-randomization time points. No differences between smokers and non-smokers were seen on placebo.

Conclusion We conclude that smoking reduces serum estrogens at both trough and after 2 h in postmenopausal women on estrogen treatment. The effect of smoking on estrogen concentrations is fully expressed in women smoking ten or less cigarettes daily. These findings indicate that the influence of smoking upon the metabolism of estrogen therapy is constant and without dose-response for standard smoking intensities.

Key words::

• CONTINUOUS
• ESTRADIOL
• GESTODENE
• HORMONE THERAPY
• PHARMACOKINETICS
• SEQUENTIAL
• SMOKING
• TRIMEGESTONE

Conflict of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Source of funding Former Schering AG (Berlin, Germany) supplied study drug, collaborated on the study protocol and funded conduct of the study (study I). Former Wyeth (US and France) supplied study drug, collaborated on the study protocol and funded conduct of the study (study II).