Joint pain and menopause

Joint pain and musculoskeletal complaints are among the most common reasons women seek medical care.¹ Gynecology and primary care are the entry point into the healthcare system for many women, although symptoms of joint pain may prompt referrals to rheumatology, orthopedics, and pain specialists to diagnose and manage musculoskeletal conditions.

WHAT ARE CAUSES OF JOINT PAIN IN MIDLIFE?

A chief complaint of joint pain in a woman aged 40 to 60 years prompts consideration of a large differential diagnosis, which includes common conditions such as osteoarthritis (OA), estrogen-deficient states, and gout. However, less-common diagnoses, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and chronic infections must be uniquely considered for women in this age group. An important initial determination when assessing a woman with joint pain is whether arthritis is present. Arthralgias identify a joint-specific problem and may be caused by OA or inflammatory arthritis. The patient may describe aching, sharp pain, or stiffness in one or multiple joints. This distinguishes arthralgias from myalgias, neuralgia, or centralized pain.

Arthritis is present when there is evidence, beyond symptoms, of a joint-specific process such as synovitis, bursitis, enthesitis (inflammation at the insertion sites of tendons), and joint effusions. Radiographic features of arthritis such as osteophytes support a diagnosis of OA, whereas erosions are more commonly associated with inflammatory conditions including RA, psoriatic arthritis, or gout.

Osteoarthritis is the most common form of arthritis in the world and with a rising incidence, carries an extremely high global burden in postmenopausal women.² Weight-bearing joints, such as knees, hips, and the lumbar spine, are predominately affected by OA; although there is also a predilection for the carpal metacarpal joints (base of the thumb), and proximal and distal interphalangeal joints in the hands. The insidious onset of symptoms, presence of bony osteophytes, both by imaging and physical exam, and history of prior joint injury all point to OA as a source of joint pain.

Joint pain in menopause tends to involve multiple joints rather than as presenting as monoarthritis, as seen in crystalline arthritis, Lyme disease, or a mechanical injury. Women describe pain and stiffness in multiple joints without obvious swelling. In general, joint pain during menopause does not result in a destructive joint or arthritic process, but it can be very disabling. There are no biomarkers or gold-standard tests to diagnose joint pain due to estrogen-deficient states; although it will often present in the context of other menopause symptoms (ie, vasomotor, mood, sleep dysregulation).

WHAT IS THE BEST WAY TO EVALUATE JOINT PAIN IN MIDLIFE WOMEN?

Inflammatory arthritis can be distinguished from OA, with its striking morning stiffness, joint swelling, synovitis, and warmth. Rheumatoid arthritis affects 1% of the population, is more common in women, and has a peak age of onset between 30 and 60 years. Consider RA in women with joint issues specific to the hands or wrists. The presence of autoantibodies, specifically rheumatoid factor and anticyclic citrullinated peptide (anti-CCP) antibodies can be helpful in distinguishing RA from other causes of joint pain. Anti-CCP antibodies may be detectable 2 to 3 years before the development of clinical RA; hence, a useful tool in diagnosing early disease. Inflammatory arthritis, such as psoriatic arthritis, gout, and pseudogout (ie, calcium pyrophosphate disease,) may present with wrist, knee, foot, or ankle involvement and should be considered if inflammatory features are present in a monoarthritic or oligoarthritic (between two and four joints) pattern.

Many systemic autoimmune diseases that disproportionately affect women—SLE, Sjogren disease, systemic sclerosis, and idiopathic inflammatory myositis—have inflammatory arthritis as a key feature. Hence, if arthritis is accompanied by skin changes (skin thickening, psoriasis, photosensitivity, inflammatory rash), cytopenias, Raynaud’s phenomenon, cough (suggestive of evolving interstitial lung disease), or profound proximal weakness, then a systemic autoimmune disease should be considered.

Arthralgias may not be arthritis but caused by acute or chronic viral infections, medication toxicity (statins, bisphosphonates, fluroquinolones), overuse injuries, vitamin deficiencies (notably vitamin D), food sensitivity (celiac disease, gluten-sensitivity), endocrinopathies (thyroid dysfunction), or estrogen-deficiency.

WHAT IS THE EFFECT OF ESTROGEN DEFICIENCY ON JOINT PAIN?

During menopause, 70% of women report musculoskeletal symptoms.³ In certain Southeast Asian and South Asian populations, joint pain is reported even more frequently than vasomotor symptoms.⁴

Estrogen receptors are present in bone (which influences osteoclast and osteoblast activity), articular cartilage, synovial membranes, and muscles and tendons.² Hence, estrogen-deficient states affect all musculoskeletal systems. A key example of this is an observational study of women aged 45 to55 years that found that self-reported joint pain and stiffness were common and significantly more likely to occur in postmenopausal than in premenopausal women; whereas no association was seen with chronologic age.⁵ Up to 40% of patients treated for estrogen-receptor positive breast cancer with aromatase inhibitors to dramatically lower circulating levels of estrogen report joint and muscle pain and develop new carpal tunnel syndrome or tenosynovitis.

WHAT IS THE INITIAL APPROACH TO MANAGEMENT OF JOINT PAIN IN MENOPAUSE?

Management of joint pain in menopause should initially focus on identifying and treating arthritic processes, such as OA, new autoimmune disease, or vitamin deficiencies and assessing for additional menopause symptoms.

All menopausal women, but especially women with joint pain, should be counseled on the importance of exercise, specifically resistance exercise, to treat joint symptoms and maintain and improve muscle mass and bone health and to prevent sarcopenia. Low-impact, but high-intensity, exercise can protect joints while building muscle. Women new to resistance training may benefit from a physical therapy referral for supervised instruction on a progressive home-based resistance exercise program. Nonsteroidal anti‑inflammatory drugs may provide some relief from joint symptoms and can be prescribed in a controlled and monitored setting. There is no role for corticosteroids or immunosuppressive agents to treat joint pain associated with menopause.

IS THERE A ROLE FOR HORMONE THERAPY TO TREAT JOINT PAIN IN MENOPAUSE?

The effect of estrogen on inflammation is complex because estrogen-receptor signaling can induce or suppress proinflammatory cytokine production, depending on the cell type and estrogen level.² The high-estrogen state of pregnancy in autoimmune disease is a dramatic example of such, as it may induce a more tolerant immune state and improvement of some autoimmune diseases such as RA, while other diseases, such as SLE, may flare, depending on disease phenotype.

There are no large randomized, controlled trials (RCTs) looking specifically at hormone therapy (HT) as a treatment for joint pain during menopause.

In the Women’s Health Initiative (WHI), approximately 77% of participants in the estrogen-alone arm of the WHI reported joint pain at baseline, before initiating HT. Persons who received HT showed more relief of these symptoms compared with those who received placebo, although differences were modest. Hormone therapy was also shown to significantly reduce the incidence of new musculoskeletal symptoms.⁶ When HT was discontinued at the end of the combined therapy arm of the WHI trials, pain and stiffness was reported by 36% of participants assigned HT.⁷ In a smaller RCT evaluating the effect of combined HT on health-related quality of life, significantly fewer women in the conjugated equine estrogen 0.625 mg/medroxy-progesterone acetate 2.5 mg group reported joint and muscle pain than in the placebo group.⁸

Further research is needed to clarify HT’s role in managing menopause joint pain, including its effects on conditions like tendonitis, adhesive capsulitis, arthritis, and body composition.

KEY SUMMARY POINTS

• Joint pain due to estrogen deficiency is an extremely common, yet frequently overlooked, condition.

• To confirm estrogen deficiency due to menopause as the cause of joint pain, other possible diagnoses must first be systematically ruled out and any treatable conditions addressed. This diagnostic process is complex, because many conditions exhibit higher prevalence in women, with peak incidence occurring during perimenopause and early postmenopause.

• After ruling out autoimmune disease and other causes of joint pain, estrogen deficiency must be considered, especially if symptoms such as hot flashes, body composition changes, mood swings, sleep issues, or mental health changes are present.

• Hormone therapy may play a therapeutic role in arthralgias associated with estrogen deficiency, although more research needs to be completed to determine timing, duration, and dose to treat this specific menopause symptom.

CLINICAL RECOMMENDATIONS

• Consider estrogen-deficient states as a cause of joint pain in women, especially in the presence of additional menopause symptoms.

• Recommend key nonpharmacologic interventions to manage musculoskeletal symptoms of menopause. Prescribe a progressive resistance exercise program with low-impact strength training to preserve muscle mass, improve bone density, and reduce joint pain. Ensure adequate nutrition with protein to mitigate sarcopenia and metabolic contributors to musculoskeletal symptoms.

• Consider hormone therapy when clinically appropriate for menopausal women experiencing joint pain. Evidence suggests that hormone therapy can confer significant improvements in symptoms such as arthralgia and myalgia; however, large-scale randomized, controlled trials specifically addressing joint and musculoskeletal outcomes in the context of menopause symptom management remain necessary to further clarify efficacy and safety profiles.

Coming next in the Step-by-Step series: Carolyn Bernstein, MD, FAHS, Lavine Family Endowed Chair in Neurology, Brigham and Women’s Hospital, associate professor of Neurology, Harvard Medical School, describes the effect of the menopause transition on patients with migraine and explains what factors to consider if these patients need hormone therapy.

This article is part of the ongoing series Menopause Step-by-Step, a monthly Menopause education feature.⁹ The Editors of this series are Dr. Cynthia Stuenkel, Dr. Cheryl Cox Kinney, and Dr. Isaac Schiff.