The influence of smoking on uterine bleeding during continuous and interrupted oral hormone therapy

To study the influence of smoking on uterine bleeding patterns during continuous and interrupted oral hormone therapy (HT).

Using a post-hoc strategy, we included five oral HT groups from three studies. The therapies consisted of continuous estrogen (estradiol, estradiol valerate or piperazine estrone sulfate) in combination with continuous progestogen (cyproterone acetate, gestodene or norethisterone acetate) or in combination with interrupted progestogen (norethisterone) given on days 4-6, 10-12, 16-18, 22-24 and 28-30. A total of 145 healthy postmenopausal women (54 smokers and 91 non-smokers), who had been followed for 2 years, were included in the analyses. Uterine bleeding data were collected from bleeding calendars.

In general, smoking women experienced significantly less days with uterine bleeding per cycle than non-smoking women during continuous and interrupted HT (0.53 +/- 0.1 vs. 1.6 +/- 0.1; p < 0.001). Smoking women were also more likely than non-smoking women to be amenorrheic during these therapies (48.2% vs. 29.7%; p < 0.05). Finally, more smoking than non-smoking women attained amenorrhea during HT (94.4% vs. 76.9%p < 0.01).

In healthy postmenopausal women, smoking may reduce uterine bleeding during interrupted and continuous HT regimens containing a broad selection of estrogens and progestogens. Further study with appropriate stratification for smoking status is warranted.