Abstract
Aromatase inhibitors (AIs) have become the standard adjuvant therapy of postmenopausal breast cancer survivors. AIs induce a reduction of bioavailable estrogens by inhibiting aromatase, which would be expected to induce alterations in body composition, more extensive than induced by menopause. The objectives are to examine the impact of AIs on (1) DXA-scan derived body composition and (2) gonadal hormone levels. This is a sub-analysis of a 2-year double-blind, placebo-controlled, randomized trial of 82 women with nonmetastatic breast cancer, newly menopausal following chemotherapy, who were randomized to risedronate (35 mg once weekly) versus placebo, and stratified for their usage of AI versus no AI. Outcomes included DXA-scan derived body composition and gonadal hormone levels. As a group, total body mass increased in women over 24 months. Women on AIs gained a significant amount of lean body mass compared to baseline as well as to no-AI users (P < 0.05). Women not on an AI gained total body fat compared to baseline and AI users (P < 0.05). Free testosterone significantly increased and sex hormone binding globulin (SHBG) significantly decreased in women on AIs compared to no AIs at 24 months (P < 0.01) while total estradiol and testosterone levels remained stable. Independent of AI usage, chemotherapy-induced postmenopausal breast cancer patients demonstrated an increase of total body mass. AI users demonstrated maintenance of total body fat, an increase in lean body mass and free testosterone levels, and a decrease in SHBG levels compared to no-AI users. The mechanisms and implications of these changes need to be studied further.
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Acknowledgments
All funding sources supporting publication of a work or study are as follows. NIH/NIDDKD (K24: DK062895-05): awarded to Dr. Greenspan. A Procter and Gamble and Sanofi-Aventis noncompany-sponsored trial grant: awarded to Dr. Greenspan. NIH/NCRR (M01-RR00056): awarded to the University of Pittsburgh. NIH/NCRR (RR024154): awarded to Dr. Steven E. Reis. John A. Hartford foundation (2004-0485): provided support for assays. None of these funding agencies were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript. Risedronate, matching placebo, calcium, and vitamin D supplements were provided by Procter and Gamble, Inc. We are indebted to the nursing, professional, laboratory, dietary, administrative, and study staff of the Clinical Translational Research Center of Montefiore University Hospital and Osteoporosis Prevention and Treatment Center at the University of Pittsburgh. We acknowledge the members of the Data and Safety Monitoring Board for their oversight of the study.
Conflict of interest
Dr Greenspan has received grant-support from Procter and Gamble, Inc., Sanofi-Aventis, Amgen, and Lilly. Dr Greenspan also serves as a consultant for Merck. Dr. Perera has received funding in the past from Eli Lilly and Co., Ortho Biotech, LLC, Teva Neuroscience for observational research. All other authors have no conflict of interest.
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van Londen, G.J., Perera, S., Vujevich, K. et al. The impact of an aromatase inhibitor on body composition and gonadal hormone levels in women with breast cancer. Breast Cancer Res Treat 125, 441–446 (2011). https://doi.org/10.1007/s10549-010-1223-2
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DOI: https://doi.org/10.1007/s10549-010-1223-2