In an exploratory analysis of the KARISMA trial, we took advantage of the full 48-item KARISMA symptom questionnaire to describe the complete side effect spectra at different doses of tamoxifen in healthy women.
We found that symptoms and adherence are influenced by menopausal status. Premenopausal women on 20 mg standard dose decreased in weight and waist circumference as well as in breast sensitivity. In addition, postmenopausal women reported higher symptom severity across all doses and discontinuation rate was two-fold compared to premenopausal women.
We identified five symptoms which constitute the greatest magnitude of severity change after 20 mg tamoxifen exposure, independent of menopausal status: hot flashes, night sweats, cold sweats, vaginal discharge and muscle cramps. Interestingly, we did not find any increase in severity scores in ten pre-defined psychological symptoms.
When comparing the top5 symptoms in premenopausal women randomized to low-dose (2.5, 5 mg) versus high-dose (10, 20 mg), the mean change was 34% lower in the low-dose group. No dose dependent difference was seen in postmenopausal women.
Our findings give new insights which may influence future dosing strategies of tamoxifen in both the adjuvant and preventive settings.