Quality of life assessment in a chemoprevention trial: Fenretinide and oral or transdermal HRT

Background: Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) relief menopause symptoms, but may increase breast cancer risk, while the effects of transdermal estradiol (E2) and MPA are less known. In previous studies, fenretinide decreased second breast malignancies in premenopausal but not in postmenopausal women, suggesting a hormone-sensitizing effect. We have evaluated the quality of life through a self-administered questionnaire during a randomized study of oral CEE or transdermal E2 and fenretinide or placebo. Methods: A total of 226 postmenopausal women were randomly assigned to either CEE 0.625 mg/day and placebo (n = 55), or CEE and fenretinide 100 mg/bid (n = 56), or E2, 50 μg/day and placebo (n = 59), or E2 and fenretinide (n = 56) for 12 months. Sequential MPA 10 mg/day was added in all groups. Treatment effects were investigated using a validated questionnaire, the Menopause Quality of Life questionnaire (MENQOL). Results: Oral CEE and transdermal E2 have a comparable activity in reducing menopausal symptoms (p = ns). Both routes ameliorate significantly the symptoms after 1 year of treatment (p <0.0001). Fenretinide does not modify the effects of hormonal replacement therapy. Conclusions: Oral CEE and transdermal E2 have similar effect on menopausal symptoms relief. The choice of the best estrogen replacement therapy (ERT) route should be decided based on a careful analysis of all the clinical aspects of every subject, considering that transdermal therapy may have a safer effect on the cardiovascular system.