Real-World Study Backs Menopausal Hormone Therapy for Stronger Bones

CHICAGO — Menopausal hormone therapy was associated with a reduced risk of low bone mineral density (BMD) among postmenopausal women in a retrospective cohort study.

Among the 387 women analyzed, low BMD — defined as osteopenia or osteoporosis — was less common for those taking hormone therapy versus those not receiving it (31.8% vs 56.2%, P<0.001), reported Diego Espinoza-Peralta, MD, MSc, of the Investigación Médica Sonora in Mexico.

On multivariable adjustment, the likelihood of low BMD was 69% lower with hormone therapy (OR 0.31, 95% CI 0.19-0.50).

“This association remained essentially unchanged in multiple sensitivity analyses” that adjusted for hypertension, chronic kidney disease, physical activity, and calcium supplementation, Espinoza-Peralta said at ENDO 2026, the annual meeting of the Endocrine Society.

Postmenopausal women taking hormone therapy also had significantly higher T-scores at two of the primary sites evaluated for low BMD: the lumbar spine (-0.62 vs -1.02, P<0.001) and the total hip (-0.32 vs -0.81, P<0.001).

“Menopausal hormone therapy appears to independently protect bones, not just by coincidence,” Espinoza-Peralta said in a statement. “Clinicians may begin to weigh its benefits more carefully, especially in women early after menopause, potentially improving long-term health and quality of life.”

Hormone therapy has long been indicated for preventing postmenopausal osteoporosis and fractures, but uptake over the past two decades has been low, with a major deterrent for women and their physicians being the long-standing boxed warning about risks for cancer, stroke, blood clots, heart attacks, and dementia based on findings from the 2002 Women’s Health Initiative study.

That same trial showed a 34% lower risk for hip fracture, a 34% lower risk for vertebral fractures, and a 23% lower risk of other osteoporotic fractures with hormone therapy, over roughly 5 years of median follow-up.

According to the FDA, an estimated 2 million women ages 46 to 65 received a prescription for menopausal hormone therapy in 2020 out of 41 million eligible women.

However, the regulatory landscape started shifting last year at the FDA, and new labeling for a number of hormone therapies no longer carries the boxed warnings, though the prescribing information still notes the potential risks lower down.

Clinical guidance still calls for a nuanced approach, however.

According to the Endocrine Society’s osteoporosis guidelines, certain postmenopausal women at high risk of fracture are recommended to use hormone therapy to prevent all fracture types. However, it’s not recommended for all women, such as those with breast cancer, prior myocardial infarction or stroke, or those over the age of 60 or more than 10 years past menopause.

“Systemic estrogen still comes with potential risks in certain individuals that should be reviewed in detail with women initiating therapy,” the Menopause Society warned at the time of the FDA label changes.

Espinoza-Peralta’s group assessed postmenopausal women who underwent dual-energy X-ray absorptiometry (DXA) at an endocrine clinic from 2021 to 2025. To minimize inter-operator variability, all DXA measurements were acquired using a single densitometry system and performed by the same certified bone densitometry technician and certified clinical densitometrist.

Of the 387 women included, the average age was about 60 years, mean body mass index was 29.2, a third used hormone therapy, and the average time since menopause was 11.1 years. Baseline 25(OH) vitamin D levels were 22.2 ng/mL, and 9% were current smokers.

Additionally, 52% had type 2 diabetes, 62% had hypertension, and 8% had chronic kidney disease. More women taking hormone therapy were also taking calcium supplementation (35.7% vs 24%, P=0.02).

While hormone therapy was associated with a protective benefit, current smoking and more years since menopause both emerged as trends toward higher odds of low BMD.

Espinoza-Peralta noted that the data should be interpreted with caution. “As with any observational study, several limitations should be acknowledged,” he said. These included the retrospective observational design, the potential for healthy-user bias, a lack of detailed information on menopausal hormone therapy duration and formulation, and the absence of fracture outcomes data.