Your Bones Are Listening: How Estrogen and Inflammation Redefine Midlife Musculoskeletal Health

Nov 3 / Jocelyn Wittstein, MD
For decades, clinicians attributed women’s midlife joint pain, stiffness, and reduced mobility to “normal aging.” But new research reveals a more precise—and far more actionable—explanation.

As orthopedic surgeon Dr. Jocelyn Wittstein (Duke University) shared during her Perry Academy masterclass, the musculoskeletal changes of midlife are not simply wear and tear. They’re the downstream effects of hormonal and inflammatory shifts that begin long before menopause.

“Estrogen is an anti-inflammatory hormone for the musculoskeletal system. When it falls, inflammation rises — and women feel it long before menopause.” (Wittstein, Perry Academy Webinar, 2025)
This perspective reframes perimenopause as a critical window for early intervention—not only for cardiovascular and metabolic health, but also for joint integrity, muscle function, and skeletal resilience.

Perimenopause also starts in the joints, not just the ovaries


Bone density loss accelerates years before the final menstrual period, driven by fluctuating rather than absent estrogen. A longitudinal Vietnamese cohort study found the first major decline in bone mineral density (BMD) between ages 45–49, with perimenopausal women losing approximately 4.3% of bone density in just two years—twice the rate seen in age-matched controls (Nguyen et al., cited by Wittstein, 2025).

These findings challenge the assumption that bone loss begins only after menopause. The changes start earlier, in the transitional years when ovulation becomes inconsistent and estradiol levels fluctuate dramatically.

By the time most women reach menopause, the silent erosion of bone has already begun—often without symptoms, until pain, fractures, or reduced strength emerge.


Inflammation is not inevitable

Estradiol regulates inflammatory cytokines such as TNF-α and IL-6, both implicated in cartilage degradation and synovial inflammation (Wittstein et al., 2024). When estrogen levels fall, these pathways activate, increasing inflammation and accelerating tissue breakdown.

The consequences are visible across the musculoskeletal system:

71–77% of perimenopausal women report joint or muscle pain.
Women are 35% more likely than men to develop osteoarthritis after age 50.
Risk of adhesive capsulitis (frozen shoulder) doubles in women not using systemic estrogen therapy (Wittstein & Wright 2024; NAMS presentation 2022).

These are not “idiopathic” aches or random aging phenomena. They’re hormonally mediated inflammatory states—predictable, measurable, and, in many cases, preventable.

Dr. Wittstein emphasized that understanding these hormonal influences allows practitioners to move from reactive treatment to proactive prevention.


Load is Medicine

For decades, women were told to avoid high-impact or heavy-resistance exercise as they aged. Yet evidence now shows the opposite: mechanical loading is one of the most potent stimuli for bone formation and musculoskeletal maintenance.

The LIFTMOR Trial (Watson et al., 2018) demonstrated that high-intensity resistance training (80–85% of one-repetition maximum) increased lumbar spine bone density by 3% and hip bone density by 2% in osteopenic postmenopausal women—without any increase in injury risk.

Impact-based programs are equally effective. As Wittstein noted, jumping or heel-drop exercises that generate forces three times body weight improved hip bone density within five months (Vainionpää et al., cited by Wittstein, 2024).

The message is clear: carefully prescribed strength and impact training are not only safe for midlife women—they’re essential for long-term musculoskeletal health.

Hormone therapy supports more than symptom relief — it protects bone, cartilage, and connective tissue

Beyond alleviating vasomotor or mood symptoms, systemic estrogen therapy has measurable structural effects. It is FDA-approved for the prevention of osteoporosis, and its musculoskeletal benefits are supported by decades of randomized controlled trials.

A meta-analysis of 28 RCTs showed:

~30% reduction in hip fractures
~40% reduction in vertebral fractures (WHI Collaborative Group, cited by Wittstein, 2024)

Estrogen also preserves cartilage thickness and improves joint function by acting directly on estrogen receptors in synovial tissue. Clinically, patients on appropriate hormone therapy often report not just improved comfort but better mobility and exercise tolerance—critical for maintaining independence and preventing frailty.

Clinical Implications

Whether you manage hormone therapy, prescribe exercise, or counsel on nutrition, musculoskeletal health should be part of every perimenopause care plan.

Early identification and multidisciplinary intervention—combining targeted exercise, dietary optimization, and hormone management where appropriate—can prevent decades of avoidable pain, immobility, and fracture risk.

Yet most professional training still treats menopause as a static endpoint rather than a dynamic endocrine transition that reshapes nearly every tissue system.

This gap in education is what Perry Academy was built to close.


About Perry Academy

Perry Academy is a CME/CE-accredited education platform translating emerging menopause research into multidisciplinary clinical practice. Our faculty includes Dr. Mary Jane Minkin, Suzanne Gilberg, MD Stacy T. Sims, PhD Jayne Morgan, M.D. leaders in women’s health.

Members gain access to:

  • Live and on-demand expert sessions
  • Multidisciplinary case studies across orthopedics, endocrinology, cardiology, nutrition, and mental health
  • Downloadable clinical tools and patient handouts
  • A professional community advancing evidence-based midlife care

“Perimenopause is the decade to act — not react.” — Dr. Jocelyn Wittstein, Duke University

The science is clear. The next step is implementation.