Objective: We wished to study the influence of smoking upon the occurrence of breast tenderness during oral estrogen-progestogen therapy (EPT).
Methods: Data from 626 healthy postmenopausal women participating in three double-blind, randomized, controlled long-term trials of EPT versus placebo were included. The studies covered sequential, continuous and interrupted regimens of estradiol opposed by a selection of progestins. All studies were mono-center studies and performed in the period 1988-1997. Data on breast tenderness were collected from adverse event reporting and information on smoking status was obtained by interview.
Results: Smoking was associated with an earlier age at menopause (difference: 1.3 years, p < 0.001) and a slightly lower body mass index (difference: 0.8 kg/m2, p < 0.01). Smoking women in the EPT groups had significantly lower on-treatment estradiol levels compared to non-smoking women (p < 0.001), whereas no differences were observed in the placebo group. In parallel, the incidence of breast tenderness during EPT was reduced by about one-half (p < 0.001) in smokers compared to non-smokers, whereas no differences were seen on placebo.
Conclusion: Current smoking reduces the incidence of breast tenderness in women receiving oral EPT. This may be caused by the increased degradation of estradiol during smoking.