The influence of smoking on uterine bleeding during sequential oral hormone therapy

Objective To study the influence of smoking on uterine bleeding patterns during sequentially administered oral hormone therapy (HT). Methods Using a post-hoc strategy, we included four sequential oral HT groups from two studies. The therapies consisted of estradiol from days 1 to 28 (estradiol or estradiol valerate) and progestogen (levonorgestrel or gestodene) on days 17-28. A total of 111 healthy, early postmenopausal women (38 smokers and 73 non-smokers) followed for 2 years were included in the analyses. Uterine bleeding data were collected from bleeding calendars. Results On the regimen containing levonorgestrel, smoking women had a cyclical bleeding significantly earlier than non-smoking women (about 2 days' difference). Moreover, smoking women had significantly longer bleeding than non-smoking women (about 1 day in difference). This was in contrast to the three regimens containing gestodene, where smoking seemed to have far less influence on uterine bleeding. Conclusions On a regimen containing levonorgestrel, smokers exhibit an earlier and longer uterine bleeding than do non-smokers. This is in contrast to regimens containing gestodene, where smoking women are less likely to differ from non-smoking women with regard to bleeding. This indicates that smoking influences progestogen metabolism, and that this influence may vary with different progestogens. Further studies are needed.