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

To study the influence of smoking on uterine bleeding patterns during sequentially administered oral hormone therapy (HT).

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.

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.

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.