To the Editor: The data from the Women's Health Initiative (WHI) provide evidence of an increased risk of cardiovascular disease and breast cancer with use of estrogen/progestin among women who experienced natural menopause.1 The mean age at enrollment in the WHI was 63 years, and most participants (74%) had never used hormone replacement therapy. Data on age at menopause or years since menopause were not provided. In their accompanying Editorial, Drs Fletcher and Colditz2 concluded that healthy postmenopausal women should not use estrogen/progestin therapy as a means to prevent chronic disease. These conclusions, however, may not necessarily apply to women who experience menopause in their 30s or 40s. Approximately 1% of women experience premature ovarian failure (natural menopause before 40 years) and 5% experience natural menopause before 45 years.3 There is evidence suggesting that women who experience premature or early natural menopause are at increased risk of all-cause and cardiovascular-related mortality.4,5 The risks and benefits of hormone replacement therapy among these women remain to be evaluated.