According to the National Center for Health Statistics, an estimated 68% of U.S. adults are either overweight or obese, the majority being female.1 The effect of weight gain on female health is pervasive and is linked to such prevalent diseases as diabetes, arthritis, cardiovascular disease, and pelvic organ prolapse (POP). Pelvic organ prolapse, consisting of anterior, apical, and posterior support defects, affects, on average, up to 50% of the female population in the United States, with prevalence rates varying among different populations from 30% to 93%.2,3 The estimated lifetime risk of surgery for POP and/or urinary incontinence by age 80 years is approximately 11%.4 In 1997, almost 226,000 (22.7 per 10,000) inpatient surgical procedures were performed in the United States to correct this condition,5 costing more than 1 billion dollars. Indeed, POP is one of the three most common reasons for hysterectomy in the United States, accounting for 15-18% of procedures in all age groups, and is the leading indication for hysterectomy in postmenopausal women.6,7 Further, an estimated 13-30% of women who have prolapse surgeries will need a reoperation within 5 years.4,8 Numerous factors, including age, ethnicity, parity, obesity, and history of hysterectomy, have been found to be associated with POP.9,10 One recent study demonstrated that hysterectomy, particularly performed vaginally, nearly quadrupled the risk for subsequent prolapse surgery.11 Despite our knowledge of the natural history of POP disorders, little is known about the effect of weight change on prolapse progression or regression. In a cross-sectional study of postmenopausal women who enrolled in the Women's Health Initiative (WHI) Hormone Therapy Clinical Trial, the risk of having uterine prolapse, rectocele, or cystocele was 30-50% higher in women with body mass indexes (BMIs) of 25 or higher than in those with BMIs of 24.9 or lower (BMI is calculated as weight (kg)/[height (m)]2).9 However, longitudinal effects of being overweight or obese on prolapse development are less well studied. Of particular interest to clinicians is the question of whether being overweight or obese is a modifiable risk factor for POP. The purpose of this secondary analysis of the WHI Estrogen plus Progestin (E+P) Clinical Trial was to evaluate the relationship between change in weight and POP progression/regression in postmenopausal women during a 5-year period.