Anneleen Lintermans1, Dirk Vanderschueren2, Johan Verhaeghe3, Kathleen Van Asten4, Ivo Jans5, Erik Van Herck6, Annouschka Laenen7, Robert Paridaens8, Jaak Billen5, Steven Pauwels9, Pieter Vermeersch9, Hans Wildiers8, Marie-Rose Christiaens10, Patrick Neven11. 1. Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: anneleen.lintermans@uzleuven.be. 2. Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. 3. Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Gynecology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. 4. Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. 5. Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. 6. Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. 7. Electrical Engineering (ESAT-SISTA), KU Leuven, Herestraat 49, 3000 Leuven, Belgium. 8. Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Multidisciplinary Breast Center, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; General Medical Oncology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. 9. Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. 10. Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Gynecology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; Multidisciplinary Breast Center, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. 11. Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Gynecology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; Multidisciplinary Breast Center, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: patrick.neven@uzleuven.be.
Abstract
BACKGROUND: Aromatase inhibitors (AIs) frequently induce or enhance musculoskeletal problems (AI-induced musculoskeletal syndrome (AIMSS)) which sometimes are debilitating. Apart from low oestrogen levels, underlying mechanisms are unknown and likely multiple. We previously hypothesised a role for the growth hormone/insulin like growth factor-I (IGF-I) axis. Here, we report the effect of tamoxifen and AI on IGF-I, IGF binding protein-3 (IGFBP-3) and oestrogen levels from a prospective study. MATERIALS AND METHODS: Postmenopausal women with an early breast cancer scheduled to start adjuvant endocrine therapy with an AI or tamoxifen were recruited. A rheumatologic questionnaire was completed and serum was collected for assessment of IGF-I, IGFBP-3 and oestrogen levels. Re-evaluation was done after 3, 6 and 1 2months of therapy. RESULTS: 84 patients started on tamoxifen (n=42) or an AI (n=42). 66% of the latter group experienced worsening of pre-existing or de novo complaints in joint and/or muscle, compared to 29% of tamoxifen-treated patients. AI therapy resulted in elevated IGF-I levels with a statistically significant increase at 6months (p=0.0088), whereas tamoxifen users were characterised by a decrease in IGF-I levels at all follow-up times (p<0.0004). No effect on IGFBP-3 was seen in the latter group. AI-users, however, showed decreased IGFBP-3 levels at 12 months (p=0.0467). AIMSS was characterised by a decrease in IGFBP-3 levels (p=0.0007) and a trend towards increased IGF-I/IGFBP-3 ratio (p=0.0710). CONCLUSION: These findings provide preliminary evidence that AI-induced musculoskeletal symptoms are associated with changes in the growth hormone (GH)/IGF-I axis.
BACKGROUND: Aromatase inhibitors (AIs) frequently induce or enhance musculoskeletal problems (AI-induced musculoskeletal syndrome (AIMSS)) which sometimes are debilitating. Apart from low oestrogen levels, underlying mechanisms are unknown and likely multiple. We previously hypothesised a role for the growth hormone/insulin like growth factor-I (IGF-I) axis. Here, we report the effect of tamoxifen and AI on IGF-I, IGF binding protein-3 (IGFBP-3) and oestrogen levels from a prospective study. MATERIALS AND METHODS: Postmenopausal women with an early breast cancer scheduled to start adjuvant endocrine therapy with an AI or tamoxifen were recruited. A rheumatologic questionnaire was completed and serum was collected for assessment of IGF-I, IGFBP-3 and oestrogen levels. Re-evaluation was done after 3, 6 and 1 2months of therapy. RESULTS: 84 patients started on tamoxifen (n=42) or an AI (n=42). 66% of the latter group experienced worsening of pre-existing or de novo complaints in joint and/or muscle, compared to 29% of tamoxifen-treated patients. AI therapy resulted in elevated IGF-I levels with a statistically significant increase at 6months (p=0.0088), whereas tamoxifen users were characterised by a decrease in IGF-I levels at all follow-up times (p<0.0004). No effect on IGFBP-3 was seen in the latter group. AI-users, however, showed decreased IGFBP-3 levels at 12 months (p=0.0467). AIMSS was characterised by a decrease in IGFBP-3 levels (p=0.0007) and a trend towards increased IGF-I/IGFBP-3 ratio (p=0.0710). CONCLUSION: These findings provide preliminary evidence that AI-induced musculoskeletal symptoms are associated with changes in the growth hormone (GH)/IGF-I axis.
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