Smoking and E2/P4 dosage
Among postmenopausal women, smoking has been shown to reduce the efficacy of hormone therapy.3 Researchers found that nonsmokers (never or past smokers) may benefit more from a lower E2/P4 dosage than current smokers (<15 cigarettes per day).4 (Women smoking ≥15 cigarettes per day or any e-cigarettes were excluded from REPLENISH). Compared with nonsmokers taking placebo, nonsmokers taking any dosage of E2/P4 had a significant and clinically meaningful reduction in VMS frequency and severity beginning at week 4 and maintained through week 12 (except for the E2/P4 dosage of 0.5/50 at week 4 for severity). By contrast, current smokers in any E2/P4 group had no significant VMS improvements from baseline to weeks 4 and 12 compared with placebo, and proportions of smokers who did measure some response to treatment (at both ≥50% and ≥75% levels) were not different from placebo at weeks 4 and 12. In addition, current smokers had significantly lower median levels of systemic estradiol and estrone concentrations with all E2/P4 treatment groups than did nonsmokers, despite both groups having similar estradiol and estrone concentrations at baseline.