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Abstract Menopause transition is often marked by an acceleration of visceral fat accumulation. Excess visceral fat is associated with insulin resistance and increased risk for breast cancer as well as heart disease and diabetes. We measured change in body composition (via iDXA), fasting insulin and glucose as part of an ongoing, Phase IIB trial (NCT04821141) of 6 months of bazedoxifene (BZA) + conjugated estrogen (CE) vs control with primary endpoints of change in mammographic density and breast tissue Ki-67. Participants are women ages 45-60 with vasomotor symptoms at increased risk for development of breast cancer. Methods: Visceral and total fat, lean, and total mass, were measured with iDXA (GE CoreScan™). Fasting plasma was assayed same day as drawn for total insulin using a chemiluminescence assay and glucose using a hexokinase method. Values generated were used to calculate HOMA IR (as a measure of insulin resistance) using the formula insulin µl/ml x glucose mg/dl/405. HOMA %S was calculated as 1/HOMA IR X100 as a measure of insulin sensitivity. Optimal HOMA IR is considered as ≤1; HOMA IR 1.5 is considered abnormal with 2.0 as evidence of insulin resistance. Optimal HOMA %S is 100%. Results: 24 women (12 BZA+CE, 12 Control) have completed baseline and 6-month body composition and insulin resistance assessments. Women randomized to BZA+CE were more likely to experience reduction in insulin resistance and improved insulin sensitivity despite a small weight gain over the initial 6 months. 7/12 randomized to BZA+CE had ≥15% reduction in HOMA IR vs only 2/12 controls. Three participants had HOMA IR 2 at baseline. Of these, one was randomized to BZA+CE and had a normal HOMA IR value at 6 months. The remaining two women were in the control group and saw no improvement in HOMA IR at 6 months. In addition, one woman randomized to control with normal HOMA-IR at baseline had HOMA IR 2 at 6 months. Next Steps: The improvements in insulin resistance parameters with BZA+CE are similar to those observed in our rodent studies, supporting this combination as promising for use in breast cancer risk reduction in women with vasomotor symptoms at high-risk for metabolic disease. Citation Format: Carol Fabian, Adrian Zelenchuk, Kandy Powers, Amy Kreutzjans, Krystal Pittman, Bill Hendry, Christy Altman, Erin Giles, Katherine L. Cook, Stephen Hursting, Bruce Kimler. Effect of 6 months of bazedoxifene + conjugated estrogens on body composition and insulin resistance abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-10.
Fabian et al. (Thu,) studied this question.