Why is estrogen not recommended as first-line treatment for patients who can develop osteoporosis or who have osteoporosis?

From the Guidelines

Estrogen is not recommended as first-line therapy for patients who can develop osteoporosis or who have osteoporosis due to its significant risk profile and the availability of safer alternatives. The primary concern is that estrogen therapy increases the risk of serious adverse events, as highlighted in the American College of Physicians guideline update from 2017 1. This guideline strongly recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy for the treatment of osteoporosis in women, citing moderate-quality evidence. Instead, the guideline recommends offering pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women with known osteoporosis, based on high-quality evidence 1. Key points to consider in the management of osteoporosis include:

• The benefits of treatment, such as reduction in vertebral and nonvertebral fractures
• The harms of treatment, including mild upper GI symptoms, atypical subtrochanteric fracture, and osteonecrosis of the jaw associated with bisphosphonates
• The importance of discussing patient preferences, fracture risk profile, and benefits, harms, and costs of medications when deciding on treatment
• The recommendation against bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women, based on low-quality evidence 1. Additionally, an older statement from the American Heart Association in 2001 1 discussed the risks of hormone replacement therapy, including venous thromboembolic events, gallbladder disease, and a possible increased risk of breast cancer, further supporting the cautious use of estrogen therapy. Overall, the current evidence supports the use of bisphosphonates, denosumab, and other alternatives as first-line treatments for osteoporosis, reserving estrogen therapy for specific cases where the benefits outweigh the risks.

From the Research

Estrogen Therapy for Osteoporosis

• Estrogen therapy is not typically recommended as the first line of treatment for patients who can develop osteoporosis or who have osteoporosis due to the potential risks and side effects associated with hormone therapy 2.
• The Women's Health Initiative (WHI) randomized controlled trial found that hormone therapy reduced the incidence of osteoporosis-related fractures, but the adverse effects outweighed the potential benefits on bone 2.
• However, subsequent studies have shown that low-dose and transdermal hormone therapy may be safer and more effective for preventing and treating osteoporosis, particularly in women with a high risk of fractures 2, 3.

Alternative Treatments for Osteoporosis

• Bisphosphonates, such as alendronate and risedronate, are commonly used as first-line treatments for osteoporosis due to their efficacy and safety profile 4, 5.
• Other treatments, such as raloxifene, calcitonin, parathyroid hormone (PTH), and strontium ranelate, may also be effective for preventing vertebral fractures in postmenopausal women with osteoporosis 4, 5.
• Non-pharmacological treatments, such as a healthy diet, prevention of falls, and physical exercise programs, are also important for preventing and managing osteoporosis 5.

Considerations for Hormone Therapy

• Hormone therapy may be considered for women with severe menopausal symptoms or those who are at high risk of osteoporotic fractures, but the risks and benefits must be carefully weighed 3, 6.
• The timing of hormone therapy initiation, type and route of administration, and patient-specific considerations, such as age and comorbidity status, are important factors to consider when prescribing hormone therapy 3, 6.