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

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Hormone Therapy, SERMS and Calcitonin

Tiffany Kim, MD Clinical Fellow VA Advanced Women’s Health UCSF – Endocrinology and Metabolism

I have nothing to disclose

Thanks to Clifford Rosen and Steven Cummings for use of hormone therapy and SERMS slides

Hormone Therapy

Khosla, Trends Endocrinol Metab 2012

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Cumulative Hazard 0.01 0.02 0.03 E+P Placebo Placebo E+P

Women’s Health Initiative Trial

Reduced incidence of:

• Hip fractures
• Vertebral fractures
• Other osteoporotic

fractures

• Total fractures
• Largest RCT of

hormone therapy in healthy postmenopausal women (osteoporosis?)

WHI: Concern for Risks

WHI: Estrogen Alone in Postmenopausal Women Compared to Placebo - Major Clinical Outcomes

*

* P < .05

*

Favors Treatment Favors Placebo

Source: Adapted from WHI Steering Committee 2004

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After Cessation of Estrogen, Younger Women Who Had Taken CEE‡ Had Fewer CHD Events

Age at Initiation of CEE (Average 5.9 years of use and 10.7 years of follow up)

Number

• f CHD

Events * Statistically

significant difference

Source: Anderson, JAMA 2004; LaCroix, JAMA 2011

‡ CEE: conjugated equine estrogen

Hormone Therapy: Current Use

FDA approval:

• Treatment of moderate to severe vasomotor or vulvar

and vaginal atrophy due to menopause

• When prescribed solely for the prevention of

postmenopausal osteoporosis, therapy should only be considered for women at significant risk of

• steoporosis and for whom non-estrogen medications

are not considered to be appropriate

• Special clinical circumstances

– If a woman on hormone therapy also has osteoporosis, does she need bisphosphonates as well?

Lindsay R et al. JCEM 1999;84:3076-3081

Combination therapy may improve lumbar spine BMD more than HRT alone

Potential concern: 2 anti-resorptives, over suppression of bone turnover?

Hormone Therapy Summary

• Fracture reduction: 34% at spine and hip in healthy

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
• nset and no contraindications, for bothersome

vasomotor/GU symptoms or osteoporosis prevention

• Low dose therapy: could consider adding alendronate

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Selective Estrogen Receptor Modulators (Raloxifene)

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Raloxifene has less effect on BMD than alendronate

Recker, Bone 2007

SERMs and breast cancer

• Some SERMs block estrogen receptors in breast
• Decrease the risk of estrogen sensitive (ER+)

breast cancer USPSTF: assess the risk of breast cancer in women ≥ age 50 and consider chemoprevention in those with >3% 5-year risk of breast cancer

Bazedoxifene + CEE (Duavee)

• Combination: estrogen (tx hot flushes) and

SERM (neutral on breast, antagonist at uterus), avoids progestin SE

– An option for hot flushes in a postmenopausal women with a uterus, osteoporosis prevention

• 25-40% decrease in hot flushes vs. placebo
• Improves BMD a little more than SERM, a

little less than the comparable dose of CEE

• Limited fracture data, long-term safety

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Summary

• Raloxifene:

– There are more effective drugs for reducing risk

• f fracture

– 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 Calcitonin: Background

Calcitonin receptor

Bone Osteoclast Takahashi, BoneKEy Reports 2014 Fernandez-Santos, Thyroid Hormone, InTech 2012

Calcitonin: Fracture Efficacy

• Minimal increase in spine BMD (1%-1.5%)
• Vertebral fracture reduction with 200 IU/day
• Not powered for non-vertebral fractures

Chestnut, Am J Med 2000; Chestnut, Osteoporos Int 2008

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Calcitonin: Analgesia and Long-Term Side Effects

• Placebo-controlled trials: reduces

acute pain in vertebral fractures

• FDA advisory panel: concern for

malignancy with long-term use

• Summary:

– Benefits may not outweigh risks of long-term osteoporosis treatment,

• ther effective therapies available

– Consider short-term use for significant acute pain from vertebral fracture

Ensrud, NEJM 2011

Summary

Drug Fracture Efficacy Side Effects Special Circumstances

Estrogens Hip, spine E+P: MI, stroke, PE, DVT, breast CA E: stroke, DVT Women who are already

• n estrogen for severe

menopausal symptoms Raloxifene Spine Venous thromboembolism, stroke Women who would also benefit from breast CA chemoprevention Calcitonin Spine Rhinitis Long term: malignancy? Short term use for acute pain from vertebral fracture

Use more effective drugs for patients with severe osteoporosis

THANK YOU