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drug adverse effects of aromatase inhibitors

Adverse effects: 1) see specific aromatase inhibitor 2) osteoporosis - evaluated fracture risk in all women starting aromatase inhibitor [5] - bisphosphate or other therapy for women with T-score T-score < -1.5 SD + 1 other fracture risk factor (i.e. age >65 or low body-mass index) or > 1 risk factor - zoledronate yearly or denosumab every 6 months [4,5] - oral bisphosphonate may be less effective [5] 3) joint pain musculoskeletal pain (arthralgias & myalgias) [1] may be caused by diminished estrogen levels; estrogen is thought to have anti-inflammatory properties & to inhibit pain signals - clinically significant musculoskeletal complications develop in ~50% of women treated with aromatase inhibitors [6] - development of musculoskeletal pain & arthragias during treatment is linked to better breast cancer outcomes [6] - a 2nd aromatase inhibitor should be tried if patient develops severe musculoskeletal symptoms [3] - duloxetine & exercise may be of benefit [3] - if musculoskeletal symptoms persist, tamoxifen should be tried [3] - acupuncture 2 sesson/week for 6 weeks of benefit [7] 4) vaginal dryness (20%) [2] a) safety of vaginal estrogens not known b) systemic absorption occurs with use of vaginal estrogens 1] tends to decrease as therapy continues 2] absorption highes with creams, lowest with Estrig c) vaginal lubricants (Astroglide, Replens, Lubrin) safer than vaginal estrogens 5) ovarian stimulation in premenopausal women 6) ESR1 gene mutations confer resistance to aromatase inhibitors - occur most frequently on exposure to aromatase inhibitors [8]

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DRUGS: aromatase inhibitor FORM: drug adverse effects aromatase inhibitor

References

  1. Prescriber's Letter 12(9): 2005 Aromatase inhibitors & the Risk of Arthralgias Detail-Document#: 211019 (subscription needed) http://www.prescribersletter.com
  2. Prescriber's Letter 13(5): 2006 Aromatase inhibitors and vaginal estrogen Detail-Document#: 220516 (subscription needed) http://www.prescribersletter.com
  3. Medical Knowledge Self Assessment Program (MKSAP) 16, 17. American College of Physicians, Philadelphia 2012, 2015 - Becker T, Lipscombe L, Narod S, et al. Systematic review of bone health in older women treated with aromatase inhibitors for early-stage breast cancer. J Am Geriatr Soc. 2012 Sep;60(9):1761-1767. PMID: 22985145
  4. Coleman R, de Boer R, Eidtmann H et al Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol. 2013 Feb;24(2):398-405. PMID: 23047045 - Llombart A, Frassoldati A, Paija O, Immediate Administration of Zoledronic Acid Reduces Aromatase Inhibitor-Associated Bone Loss in Postmenopausal Women With Early Breast Cancer: 12-month analysis of the E-ZO-FAST trial. Clin Breast Cancer. 2012 Feb;12(1):40-8. PMID: 22014381
  5. Hadji P, Aaprob MS, Body JJ et al Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG. J Bone Oncol. 2017 Mar 23;7:1-12. eCollection 2017 Jun. Review. PMID: 28413771 Free PMC Article http://www.sciencedirect.com/science/article/pii/S2212137417300258 - International Osteoporosis Foundation Public Release: 25-Apr-2017 New guidance for management of aromatase-inhibitor related bone loss in breast cancer. https://www.eurekalert.org/pub_releases/2017-04/iof-ngf042517.php
  6. Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - Tenti S, Correale P, Cheleschi S, et al. Aromatase inhibitors-induced musculoskeletal disorders: current knowledge on clinical and molecular aspects. Int J Mol Sci. 2020;21(16):5625 PMID: 32781535 PMCID: PMC7460580 Free PMC article https://www.mdpi.com/1422-0067/21/16/5625
  7. Hershman DL, Unger JM, Greenlee H et al Comparison of Acupuncture vs Sham Acupuncture or Waiting List Control in the Treatment of Aromatase Inhibitor-Related Joint Pain. A Randomized Clinical Trial. JAMA Netw Open. 2022;5(11):e2241720 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2798317
  8. Tan WW, Marienberg ES Fast Five Quiz: Precision Medicine in Cancer Medscape. January 06, 2023 https://reference.medscape.com/viewarticle/954083