ROLE OF CIGARETTE-SMOKING ON THE POSTMENOPAUSAL ENDOMETRIUM DURING SEQUENTIAL ESTROGEN AND PROGESTOGEN THERAPY

Objective: To study the effect of cigarette smoking on the endometrial response to sequentially combined hormone replacement therapy. Method s: Healthy, early postmenopausal women were randomly assigned to three treatment groups: estradiol (E2) sequentially combined with 75 mug of levonorgestrel (19), or 150 mug of desogestrel (20), or 10 mg of medr oxyprogesterone acetate (18). After 2 years of therapy, the hormone ef fects on the endometrium were assessed by endometrial histology; effec ts were also analyzed on biochemical markers of secretion, specificall y, secretory endometrial protein (placental protein 14) in serum, and E2 dehydrogenase and isocitrate dehydrogenase in endometrial tissue. I nformation on smoking habits was elicited by questionnaire. Results: S mokers numbered relatively more women with an atrophic endometrium (50 versus 22%) and proportionally fewer with secretory endometrium (50 v ersus 78%) (P < .05). The level of serum placental protein 14 was corr espondingly almost halved in the smokers (P < . 001). The influence of smoking was in part caused by a reduced level of serum E2, but primar ily by a non-E2-mediated eff ect. The E2 effect accounted for 38% of t he decrease in serum placental protein 14, and the non-E2-mediated smo king effect for 62%. Endometrial E2 and isocitrate dehydrogenase tende d to be lower in smokers, but not after adjustment for the reduced ser um E2 level. Conclusion: We suggest that smokers may benefit from a ho rmone combination with a higher dose of E2, even higher than expected as seen from the measurement of serum E2.