Persistent misconceptions about hormone therapy are shaping clinical practice in France, with measurable consequences for bone health in menopausal women and those receiving endocrine therapy for breast cancer (BC).

At the 38th Congress of the French Society of Rheumatology (SFR) in Paris, Rose-Marie Javier, MD, a rheumatologist at Hôpitaux Universitaires de Strasbourg, Strasbourg, France, reviewed the skeletal and pain-related effects of hormonal and antihormonal therapies in two clinical contexts: menopause and BC.

Menopause Reframed

Javier proposed that age-related estrogen deficiency more accurately reflects the underlying pathophysiology of menopause, and the key factor is the abrupt decline in ovarian estrogen production, which is only partly offset by the peripheral conversion of adrenal androgens.

Within 1 year of menopause onset, bone mineral density declines, and the bone structure becomes more fragile. In bone densitometry, a T-score below 2.5 is observed in 6% of women aged 50-55 years and in 47% of women older than 80 years.

The Women’s Health Initiative study in 2002 had a lasting negative effect on the use of menopausal hormone therapy (MHT), which combines estrogen with medroxyprogesterone acetate (MPA). Although the fracture risk for this combination was reduced, the trial reported an increased risk for BC and cardiovascular disease.

Subsequent analyses refined this interpretation:

• The elevated risk was specifically linked to MPA.
• A 2016 Finnish observational study reported lower BC mortality among women receiving estrogen alone or estrogen combined with progestins other than MPA, which is not prescribed in France.
• A 2024 study showed that the risk for ischemic heart disease and venous thromboembolism increases with oral, combined estrogen-progestin therapy but appears neutral with transdermal administration.

She outlined an age- and fracture risk-stratified approach to osteoporosis management:

• Age 50-60, particularly with vasomotor symptoms and skeletal risk: MHT
• Age 55-70 with fracture risk and consideration of BC prevention: raloxifene
• Age 66 or older with high or established fracture risk, especially hip fracture risk: bisphosphonates or denosumab
• Age 60 or older: calcium and vitamin D supplementation

Only 6% of menopausal women in France currently undergo MHT. Javier called for active efforts to address misinformation and promote appropriate prescribing to reduce osteoporotic fractures and improve quality of life.

Fracture Risk

Aromatase inhibitors (AIs) suppress the conversion of adrenal androgens to estrogens, further lowering circulating estrogen levels and increasing fracture risk. Commonly used agents include anastrozole, exemestane, and letrozole.

Tamoxifen, a selective estrogen receptor modulator, acts as an antagonist in breast tissue but as a partial agonist in bone.

Across trials, AIs are associated with comparable excess fracture risk, which is 47% higher than that of tamoxifen. Extending AI therapy beyond 5 years has not demonstrated an improvement in overall survival but has increased adverse effects.

French recommendations provide therapeutic strategies for the prevention and management of adjuvant treatment-induced osteoporosis in BC. Several European societies have issued recommendations for monitoring patients receiving AIs for BC, and two components are central:

• Baseline and follow-up bone densitometry, which remains rarely practiced in France
• Structured physical exercise, particularly muscle strengthening

Pain Adherence

Joint pain is common among patients receiving AIs and frequently leads to treatment discontinuation. A French study described four pain phenotypes: osteoarticular pain resembling osteoarthritis in the limbs, diffuse pain similar to fibromyalgia, neuropathic pain, and tendinopathy.

Several studies have demonstrated the effectiveness of resistance exercises in these patients. Proactive pain management may improve adherence to endocrine therapy and potentially influence oncologic outcomes.

This story was translated from Univadis France, part of the Medscape Professional Network.