Estrogen and Testosterone and How They Differ for Arthritis

 

“Overall, the body of evidence supports boron as a bioactive and potentially beneficial trace element that influences inflammation, immune function, and bone metabolism.”

 

In United States and Canada, roughly 1 in 4 to 1 in 5 adults are suffering from arthritis. This is the same amount suffering from chronic pain, they go hand in hand. Gout (inflammatory arthritis), which is diet related, is the most common form of arthritis. But what is rheumatoid arthritis (RA), how does it start and what are the early signs?

Symptoms, causes and risk factors

Rheumatoid arthritis is a chronic autoimmune disease affecting nearly 18 million[1] people worldwide and is a major cause of disability, particularly among older adults. In RA, the immune system mistakenly attacks the synovium—the lining of the joints—leading to persistent inflammation, pain, stiffness, and progressive joint damage. When poorly managed, the disease can shorten life expectancy by six to seven years and may also affect organs such as the heart, lungs, blood vessels, kidneys, and nerves. Early identification and treatment can prevent much of the disability associated with RA.

Early signs of rheumatoid arthritis most often include symmetrical joint pain and stiffness, especially in the hands, wrists, and feet, along with morning stiffness lasting at least an hour and joint swelling or tenderness. As RA progresses, joint deformities and reduced range of motion may develop. About 40% of patients also experience systemic symptoms such as fatigue, low-grade fever, unintended weight loss, sleep problems, and inflammation beyond the joints. The disease process is driven by genetic susceptibility combined with environmental triggers that activate immune cells and autoantibodies, leading to the formation of inflammatory tissue (pannus) and the release of cytokines and enzymes that damage cartilage and bone.

What is the cause of RA? Genetics plays a big role but environmental and lifestyle factors are also crucial in triggering disease onset. Key contributors include smoking, chronic gum disease, microbiome disruption, certain infections, inflammatory diets, vitamin D deficiency, chronic stress, hormonal changes, and exposure to environmental toxins. Additional risk factors include obesity, female sex, family history, lower socioeconomic status, and the presence of other autoimmune diseases. Rheumatoid arthritis is classified into seropositive and seronegative types based on the presence of autoantibodies, with seropositive disease often being more aggressive and more likely to cause systemic complications.

 

The early stages of RA

Researchers[2] have discovered that rheumatoid arthritis does not start at the onset of joint pain, it begins many years earlier as a hidden immune system process. By longitudinally studying people who carry antibodies associated with RA (specifically ACPA antibodies) over seven years, the team from institutions including the Allen Institute and UC San Diego found widespread systemic inflammation and significant immune cell changes long before clinical symptoms appear. These early changes include hyperactive B cells producing inflammatory signals, expansion of certain T helper cells that drive autoimmune reactions, and even epigenetic reprogramming of “naive” T cells that have never encountered a pathogen yet show altered gene regulation. Monocytes in the bloodstream also began exhibiting characteristics similar to the inflammatory cells found in affected joints.

This research provides a detailed map of the immune system’s shift toward autoimmunity in the years leading up to RA symptoms, suggesting that the disease’s destructive processes are underway far earlier than previously recognized. The findings highlight potential early biomarkers that could help doctors identify individuals most likely to develop RA, opening the door to monitoring and preventive strategies that intervene before joint damage and pain begin. Ultimately, the study supports a shift toward earlier detection and possibly prevention of the disease by stopping the autoimmune process in its earliest stages.

The gout disparity (male dominance) and the menopause shift

Research continues to support a “mirrored” prevalence between gout (men) and thyroid (women), though they are linked biologically through metabolism. So even though men and women mirror opposite conditions, they are interrelated. Men are significantly more likely to develop gout—it is 3 to 10 times more common in men than in women—, while women are up to 8 times more likely to suffer from thyroid diseases. Why? Because of women’s hormonal protection. Women have lower uric acid levels because estrogen promotes the excretion of uric acid through the kidneys but this protection drops after menopause, at which point women’s uric acid levels and gout risk begin to approach those of men. If we look at the age of onset, men typically develop gout earlier, often between ages 30 and 50, while women rarely develop it before menopause.

The thyroid disparity (female dominance)

Thyroid conditions, including Hashimoto’s and Graves’ disease, predominantly affect women. This is due to autoimmune sensitivity, which means that women are significantly more prone to autoimmune thyroid diseases—roughly 4 times more likely to have Hashimoto’s thyroiditis. Females often display a stronger immune response, which aids in fighting infections but also increases vulnerability to the autoimmune attacks that cause thyroid dysfunction. In Canada, thyroid dysfunction affects roughly 16% of women compared to 4% of men over age 45. In the U.S., about 1 in 8 women will develop a thyroid disorder during their lifetime.

The biological link

Despite their opposite prevalence patterns, these two conditions are often connected:

  • Thyroid function and uric acid: Thyroid hormones regulate the enzymes that break down and eliminate uric acid. Hypothyroidism (underactive thyroid) is associated with higher uric acid levels, which can trigger or worsen gout.
  • Increased risk: Patients with hypothyroidism have a 40% to 50% increased risk of developing gout.
  • Screening: Because of this connection, medical guidelines often recommend screening for thyroid issues in anyone who suffers from recurrent gout flares.

For women, estrogen is their protection for gout: it acts as a natural shield for them against gout thanks to natural flushing. Estrogen is a “uricosuric”, meaning it signals the kidneys to flush uric acid out through urine. The exception is during post-menopause: once estrogen drops after menopause, women’s uric acid levels rise quickly, making them vulnerable to gout for the first time.

As for men, testosterone does not protect them against gout, in fact, its presence is a primary reason men have higher uric acid levels than women. However, testosterone acts as a powerful immunosuppressant, which is likely why men have significantly lower rates of autoimmune thyroid issues.

Benefits of boron

“Reported beneficial actions of boron include arthritis alleviation or risk reduction, bone growth and maintenance, central nervous system function, cancer risk reduction, hormone facilitation, and immune response, inflammation, and oxidative stress modulation. The diverse effects of boron indicate that it influences the formation and/or activity of an entity that is involved in many biochemical processes. (…) Both animal and human data suggest that boron intakes from food should be >1.0 mg/d. Many people consume less than this amount. Thus, a low boron intake should be considered a health concern, which can be prevented by diets rich in fruits, vegetables, nuts, and pulses.”[3]

Research spanning several decades suggests that boron may play a beneficial role in reducing the risk and severity of arthritis. Early observational reports noted lower arthritis rates in regions with higher boron levels in soil, food, and water, and small human studies found that boron supplementation (typically 6–12 mg per day) improved subjective measures such as joint pain, stiffness, and mobility—particularly in people with mild to moderate osteoarthritis. Animal and cell studies provide biological plausibility, showing that boron can influence inflammatory responses and cytokine activity involved in arthritis. However, many human studies lacked rigorous controls, and well-designed, large-scale clinical trials using objective outcomes are still needed to confirm therapeutic effects.

Beyond arthritis, substantial evidence indicates that boron supports bone growth, maintenance, and strength. Animal studies consistently show that boron deprivation impairs bone formation, reduces bone density, weakens bone structure, and disrupts dental and alveolar bone health, potentially increasing osteoporosis risk. Conversely, boron supplementation has been associated with improved bone density, trabecular structure, and bone strength in animal models and some human studies, including patients with osteoporosis receiving calcium fructoborate. These findings suggest boron plays a meaningful role in skeletal health, particularly in trabecular and dental bone.

Overall, the body of evidence supports boron as a bioactive and potentially beneficial trace element that influences inflammation, immune function, and bone metabolism. While definitive clinical proof is still lacking for arthritis treatment, existing data indicate that boron intakes above 1 mg per day may help reduce inflammatory stress, support bone health, and possibly lower the risk of arthritis and osteoporosis. Increasing boron intake through boron-rich foods such as fruits, vegetables, nuts, and legumes is therefore considered a reasonable and potentially health-promoting dietary recommendation.

DMSO and P5P

According to studies, DMSO can also reduce autoimmune arthritis. The study DMSO Represses Inflammatory Cytokine Production from Human Blood Cells and Reduces Autoimmune Arthritis[4], investigated how DMSO affects inflammatory responses and arthritis using both human immune cells in the lab and an animal model of arthritis. In human blood samples stimulated with bacteria or virus particles, DMSO at low concentrations (about 0.5–2%) significantly suppressed the production of pro-inflammatory cytokines and chemokines, as well as prostaglandin E2, which are key mediators of inflammation. These effects appeared linked to DMSO’s ability to block signaling pathways involved in inflammatory activation. However, at the higher end of this range (2%), DMSO also reduced monocyte viability, suggesting a narrow window between anti-inflammatory effect and cellular toxicity.

When tested in mice with autoimmune arthritis induced by pathogenic serum, topical DMSO significantly reduced arthritis severity, including less joint inflammation and lower levels of pro-inflammatory cytokines in the joints and blood compared with untreated mice. This indicates that DMSO can mitigate inflammation and arthritis symptoms in an animal model.

The active form of vitamin B6, P5P (Balanced) could also help in case of arthritis, as it is involved in more bodily functions than any other single nutrient, and affects both our physical and mental health. P5P is recommended for many purposes, and is of special value to women. It is used in herbal medicine to help relieve premenstrual symptoms, and give relief from menopausal symptoms and menstrual pain. It acts as a calmative to ease nervous tension and help the body to handle stress. It helps soothe muscle and joint pain associated with rheumatic conditions such as rheumatoid arthritis, osteoarthritis, and/or fibrositis, as well as pain of neuralgia, such as sciatica. A minimum of 6 months’ supplementation with P5P will help to reduce loss of bone mineral density (BMD) in post-menopausal women, when combined with adequate amounts of both calcium and Vitamin D.

 

References:

 

 

 

[1] Black, Rachel J et al. 2021.

[2] He, Ziyuan et al. 2025.

[3] Nielsen Forrest H. et al. 2011.

[4] Elisia, Ingrid. 2016.