Hormone Therapy, SERMS and Calcitonin I have nothing to disclose - PowerPoint PPT Presentation

7/12/2018 Hormone Therapy, SERMS and Calcitonin I have nothing to disclose Tiffany Kim, MD Thanks to Clifford Rosen and Steven Cummings for use of Clinical Fellow hormone therapy and SERMS slides VA Advanced Women’s Health UCSF – Endocrinology and Metabolism Hormone Therapy Khosla, Trends Endocrinol Metab 2012 1

7/12/2018 Women’s Health Initiative Trial • Largest RCT of hormone therapy in 0.01 0.02 0.03 healthy postmenopausal Cumulative Hazard women (osteoporosis?) Placebo E+P Reduced incidence of: • Hip fractures • Vertebral fractures • Other osteoporotic E+P fractures Placebo • Total fractures WHI: Estrogen Alone in Postmenopausal Women WHI: Concern for Risks Compared to Placebo - Major Clinical Outcomes * * Favors Treatment Favors Placebo * P < .05 Source: Adapted from WHI Steering Committee 2004 2

7/12/2018 After Cessation of Estrogen, Younger Women Who Had Hormone Therapy: Current Use Taken CEE‡ Had Fewer CHD Events FDA approval: • Treatment of moderate to severe vasomotor or vulvar and vaginal atrophy due to menopause * Statistically significant Number • When prescribed solely for the prevention of difference of CHD postmenopausal osteoporosis, therapy should only be Events considered for women at significant risk of osteoporosis and for whom non-estrogen medications are not considered to be appropriate • Special clinical circumstances Age at Initiation of CEE – If a woman on hormone therapy also has osteoporosis, does (Average 5.9 years of use and 10.7 years of follow up) she need bisphosphonates as well? ‡ CEE: conjugated equine estrogen Source: Anderson, JAMA 2004; LaCroix, JAMA 2011 Combination therapy may improve lumbar Hormone Therapy Summary spine BMD more than HRT alone • Fracture reduction: 34% at spine and hip in healthy Lindsay R et al. JCEM 1999;84:3076-3081 postmenopausal women • Concern for side effects: CHD events, stroke, venous thromboembolism, dementia – May be due to type of estrogen, progesterone, dose • Consider in women <60 yo or <10 years of menopause onset and no contraindications, for bothersome vasomotor/GU symptoms or osteoporosis prevention Potential concern: 2 anti-resorptives, over suppression of bone turnover? • Low dose therapy: could consider adding alendronate 3

7/12/2018 Selective Estrogen Receptor Modulators (Raloxifene) 4

7/12/2018 Raloxifene has less effect on BMD than alendronate Recker, Bone 2007 SERMs and breast cancer Bazedoxifene + CEE (Duavee) • Combination: estrogen (tx hot flushes) and • Some SERMs block estrogen receptors in breast SERM (neutral on breast, antagonist at uterus), • Decrease the risk of estrogen sensitive (ER+) avoids progestin SE breast cancer – An option for hot flushes in a postmenopausal women with a uterus, osteoporosis prevention USPSTF: assess the risk of breast cancer in women ≥ • 25-40% decrease in hot flushes vs. placebo age 50 and consider chemoprevention in those with • Improves BMD a little more than SERM, a >3% 5-year risk of breast cancer little less than the comparable dose of CEE • Limited fracture data, long-term safety 5

7/12/2018 Summary • Raloxifene: – There are more effective drugs for reducing risk of fracture Calcitonin – Consider in a women with osteoporosis and at increased risk of breast cancer – Contraindicated in women with history of venous thromboembolism • BZA + CEE is an alternative for hot flushes in postmenopausal women with a uterus Calcitonin: Background Calcitonin: Fracture Efficacy Calcitonin receptor Osteoclast • Minimal increase in spine BMD (1%-1.5%) Bone • Vertebral fracture reduction with 200 IU/day • Not powered for non-vertebral fractures Fernandez-Santos, Thyroid Hormone, InTech 2012 Takahashi, BoneKEy Reports 2014 Chestnut, Am J Med 2000; Chestnut, Osteoporos Int 2008 6

7/12/2018 Summary Calcitonin: Analgesia and Long-Term Side Effects • Placebo-controlled trials: reduces Drug Fracture Side Effects Special acute pain in vertebral fractures Efficacy Circumstances Estrogens Hip, spine E+P: MI, stroke, PE, Women who are already • FDA advisory panel: concern for DVT, breast CA on estrogen for severe malignancy with long-term use E: stroke, DVT menopausal symptoms Raloxifene Spine Venous Women who would also thromboembolism, benefit from breast CA • Summary: stroke chemoprevention – Benefits may not outweigh risks of Calcitonin Spine Rhinitis Short term use for acute long-term osteoporosis treatment, other effective therapies available Long term: pain from vertebral malignancy? fracture – Consider short-term use for significant acute pain from vertebral fracture Use more effective drugs for patients with severe osteoporosis Ensrud, NEJM 2011 THANK YOU 7