Hormones and the immune system are deeply connected, influencing women's health at every stage of life. Menopause is one of the critical hormonal transitions that can impact immune function and susceptibility to autoimmune diseases.
Autoimmune diseases affect women far more often than men, with nearly 80% of cases occurring in women.(1) Hormones like estrogen and progesterone play a key role in how the immune system responds. At the same time, autoimmune conditions can impact hormonal changes, making symptoms more complex. Recognizing these connections can encourage women to take proactive measures to manage their health and improve their quality of life.
Autoimmunity and Immune System Dysregulation
The immune system is critical in protecting the body by identifying and eliminating harmful pathogens while preserving healthy tissues. This defense relies on a complex network of immune cells that work together to maintain balance and prevent harmful responses against the body’s own structures.(2)
B cells and T cells are key regulators of immune function.
B cells: These are produced in the bone marrow and generate antibodies that fight foreign invaders.
T cells: These cells mature in the thymus and are divided into two main types. Cytotoxic T cells (CD8+) directly destroy infected or abnormal cells, and helper T cells (CD4+) coordinate immune responses by signaling other immune components.
This immune regulation fails in autoimmune diseases. The immune system mistakenly identifies the body’s own tissues, such as the joints, skin, or internal organs, as threats. This results in the production of autoantibodies, which can trigger chronic inflammation and tissue damage.(2)
The Link Between Autoimmune Diseases and Menopause
Menopause is associated with significant hormonal shifts that can alter immune regulation, increase inflammation, and change immune cell activity. These alterations can contribute to the development or progression of autoimmune conditions during the menopausal transition.
The Role of Estrogen
Estrogen plays a key role in immune function by influencing inflammation, immune cell activity, and tolerance to self-antigens. Before menopause, the dominant form of estrogen is 17β-estradiol (E2), which is primarily produced by the ovaries. E2 has strong immunomodulatory effects, balancing immune responses by enhancing regulatory T cells (Tregs) that suppress autoimmunity while also stimulating B-cell activation, which supports antibody production.(3)
Ovarian function declines as menopause approaches, leading to a sharp reduction in E2 levels. The primary form of estrogen in postmenopausal women becomes estrone (E1), which is produced from androstenedione in peripheral tissues, such as fat, liver, and muscle. Unlike E2, E1 does not exert the same level of immune regulation, and its shift affects several aspects of immune function, including the following changes:(3)
Increased Inflammation: Estrogen helps control inflammation by reducing pro-inflammatory cytokines like IL-1, IL-6, and TNF-α. When estrogen levels drop, these cytokines increase, leading to chronic inflammation and higher immune system activation, which play a role in autoimmune diseases.
T-Cell Dysregulation: The thymus, which helps develop immune cells, naturally shrinks with age. Estrogen withdrawal accelerates this process, reducing the production of key immune cells like CD4+ helper T cells and regulatory T cells (Tregs). Fewer Tregs means the immune system has a harder time distinguishing between harmful invaders and the body’s own tissues, increasing the risk of autoimmunity.
B-Cell Overactivity: Estrogen helps regulate B-cell activity and autoantibody production. When levels drop, self-reactive B cells that should be eliminated may survive, increasing the risk of autoimmune diseases like lupus, where excess antibodies attack healthy tissues.
The Role of Progesterone and Androgens
Progesterone helps reduce inflammation by lowering pro-inflammatory cytokines and boosting anti-inflammatory ones like IL-10. It also suppresses overactive immune responses by limiting T-cell activation and B-cell proliferation, which helps prevent autoimmune reactions. As progesterone levels drop during menopause, these protective effects weaken, leading to higher immune activity and more inflammation.
Androgens (testosterone and DHEA-S) help control immune responses by promoting Th1 and CD8+ T-cell activity, which can suppress B-cell-driven autoimmune diseases. They also inhibit B-cell activation and reduce autoantibody production, counteracting estrogen’s immune-stimulating effects. When androgen levels decline after menopause, these regulatory functions weaken, increasing the risk of autoimmune diseases.(3)
The Link Between Hormonal Changes and Autoimmunity
Fluctuating hormone levels can contribute to immune dysregulation, increased chronic inflammation, and a weakened ability to suppress autoimmunity. This hormonal imbalance can also increase the probability of developing or worsening autoimmune disorders, especially those driven by B-cell hyperactivity and chronic inflammatory processes.(3)
Understanding these hormonal influences provides insight into why autoimmune conditions, such as rheumatoid arthritis, lupus, and multiple sclerosis, often fluctuate with hormonal changes and why symptoms may worsen after menopause. The loss of immune-regulating hormones can shift the immune system toward increased self-reactivity.
How does menopause affect specific autoimmune diseases?
The hormonal shifts that occur during menopause influence the immune system and can affect the course of autoimmune diseases.(1)
Multiple Sclerosis (MS)
MS is an autoimmune disease that affects the central nervous system, causing inflammation and nerve damage. It’s more common in women, but men often experience faster disease progression once diagnosed. The immune system’s response to hormonal changes is key to the disease's development over time.
Many women are diagnosed with MS during their reproductive years, but research shows a peak in new cases between ages 40 and 55, around the time of menopause. Estrogen decline may be a factor, as it’s linked to increased levels of pro-inflammatory cytokines (IL-1, IL-6, and TNF-α) and a decrease in anti-inflammatory cytokines, both of which are involved in MS. The loss of estrogen can also affect brain repair mechanisms, worsening cognitive decline.
Symptoms of menopause and MS overlap, including fatigue, mood changes, and cognitive difficulties, making them challenging to distinguish.
Systemic Lupus Erythematosus (SLE)
SLE is a chronic autoimmune disease that affects multiple organs and is much more common among women. Estrogen plays a key role in driving the immune response, particularly in B-cell activity and autoantibody production, which contribute to lupus.
Women with SLE tend to have higher disease activity during their reproductive years, when estrogen levels are higher. After menopause, disease flares become less frequent, but the overall damage from past flares can accumulate. Estrogen withdrawal can also contribute to cardiovascular and metabolic complications, which are already a concern for women with lupus.
Studies suggest that early menopause, surgical menopause, and oral contraceptive use may increase the risk of developing SLE.
Type 1 Diabetes Mellitus (T1DM)
T1DM is an autoimmune disease that results in the destruction of insulin-producing pancreatic β-cells. While menopause does not directly cause T1DM, it can influence disease progression and complications.
Some studies have suggested that women with T1DM may experience earlier menopause, particularly if they have microvascular complications such as diabetic nephropathy or retinopathy. Menopause also increases the risk of cardiovascular disease, which is a major concern for women with diabetes.
As hormone levels drop, insulin resistance can increase, making blood sugar management more difficult. This hormonal shift may also contribute to greater complications from diabetes.
Rheumatoid Arthritis (RA)
RA is a chronic autoimmune disease that primarily affects the joints. It’s more common in women, particularly before menopause. The decline in estrogen appears to play a role in the onset and progression of the disease.
Some studies suggest that early menopause (before age 45) is linked to a higher risk of developing RA. The immune system becomes more prone to inflammation, and estrogen’s role in regulating B cells and cytokine production is lost. Women who develop RA after menopause tend to have worse joint damage and faster functional decline, even when other factors like age and disease duration are taken into account.
Declining estrogen levels also affect bone health, increasing the risk of osteoporosis, which can further complicate joint disease. Postmenopausal women with RA are more likely to experience severe joint problems and physical disability, making menopause an important factor in disease progression.
Psoriasis
Psoriasis is an autoimmune skin condition driven by an overactive immune response. It follows a bimodal pattern, with cases often appearing around puberty or between ages 30 and 50, suggesting a link to hormonal fluctuations.
Many women report increased inflammation and skin flare-ups during the postmenopausal years, likely due to immune dysregulation. Research also shows a rise in new cases of psoriasis among women in their 60s, further supporting the link between menopause and disease activity.
How Symptoms of Autoimmune Diseases and Menopause Overlap
Many symptoms of menopause and autoimmune diseases are similar, making it difficult to distinguish between the two. Some of the most common overlapping symptoms include the following:
Fatigue
Joint pain and stiffness
Cognitive difficulties (brain fog)
Mood changes (anxiety, depression)
Hot flashes
Sleep disturbances
Muscle aches and weakness
Since menopause is driven by hormonal fluctuations, and autoimmune diseases result from immune system dysregulation, identifying the cause of these symptoms is essential. Menopausal symptoms tend to develop gradually and fluctuate, while autoimmune disease flare-ups often appear more suddenly and may be accompanied by inflammation or worsening of existing conditions.
If symptoms persist, worsen, or significantly impact daily life, consulting a physician is the best approach. A healthcare provider can assess medical history and recommend appropriate management strategies to address both hormonal changes and autoimmune conditions effectively.
Treatment Options for Women with Autoimmune Diseases During Menopause
Managing menopausal symptoms in women with autoimmune diseases requires a multifaceted approach. Research suggests that a combination of hormone replacement therapy, targeted medications, and lifestyle modifications can help alleviate symptoms, protect long-term health, and improve overall well-being.
Hormone Replacement Therapy (HRT)
HRT is commonly used to compensate for estrogen deficiency, which can contribute to bone loss, cardiovascular risks, and menopausal symptoms. Research suggests that HRT can be beneficial for women with autoimmune diseases by maintaining hormonal balance and improving quality of life. However, treatment must be individualized, considering personal risk factors and coexisting autoimmune conditions.(4)
Medications
For women with autoimmune diseases, certain medications may help manage symptoms, reduce inflammation, and support overall health:(5)
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): These are commonly used to relieve joint pain, inflammation, and discomfort associated with autoimmune conditions.
Immunosuppressive Therapies: Some cases of autoimmune-related ovarian dysfunction may benefit from immunosuppressants, though their role in preserving ovarian function is still being studied.
Disease-Modifying Anti-Rheumatic Drugs (DMARDs): Medications like methotrexate and leflunomide help control the progression of autoimmune diseases and may indirectly support ovarian health.
Biologic Therapies: These targeted treatments can help regulate immune system overactivity, potentially reducing the impact of autoimmune diseases on ovarian function.
Lifestyle and Self-Care Tips
Lifestyle modifications can play a critical role in managing symptoms and supporting overall health:(6)
Dietary Modifications
Research suggests that dietary choices can influence inflammation and immune system function:
Mediterranean Diet: The Mediterranean diet, rich in fruits, vegetables, olive oil, whole grains, nuts, and fish, has been linked to lowered risk of inflammation and better hormone regulation.
Immune-Boosting Foods: Anti-inflammatory foods like turmeric, ginger, green tea, and fermented foods help support immune balance.
Protein-Rich Foods: Protein is important for muscle maintenance, especially post-menopause, and sources like lean meats, fish, eggs, and plant-based proteins are recommended.
Calcium- and Vitamin D-Rich Foods: Dairy, leafy greens, and fortified foods support bone health and reduce the risk of osteoporosis.
Reduced Fat, Sugar, and Salt Intake: Limiting processed foods, refined sugars, and excessive salt may help reduce inflammation and metabolic disturbances.
Exercise
Regular physical activity supports hormone balance, immune function, and overall well-being:
Strength Exercises: Strength training helps maintain muscle mass, bone density, and metabolic health.
Cardiovascular Exercises: Walking, swimming, cycling, and other cardio workouts improve heart health and reduce the risk of metabolic disorders.
Flexibility and Balance Exercises: Activities like yoga and Pilates enhance mobility and reduce stress.
Engaging in at least 150 minutes of moderate exercise weekly can significantly improve long-term health.
Other Strategies
Smoking Cessation: Tobacco exposure is linked to ovarian dysfunction, worsened autoimmune disease progression, and increased cardiovascular risks.
Alcohol Moderation: While excessive alcohol can disrupt immune function and inflammation, limited consumption (e.g., red wine in the Mediterranean diet) may have some protective effects.
Sleep Optimization: Prioritizing sleep quality can help regulate immune function and reduce inflammation, lowering the risk of autoimmune flares.
Stress Management: Chronic stress can worsen autoimmune disease activity and hormone imbalances. Mindfulness, therapy, and relaxation techniques, such as meditation or deep breathing exercises, can improve resilience and symptom control.
Empowering Women with Autoimmune Diseases Through Menopause
Menopause marks a significant hormonal transition that can influence the course of autoimmune diseases, adding complexity to symptom management and overall health. The interplay between hormones and immune function highlights the need for a personalized approach to treatment. While menopause may exacerbate inflammation and immune dysregulation, research suggests that a combination of HRT, targeted medications, and lifestyle adjustments can help mitigate symptoms and improve quality of life.
Women navigating menopause with an autoimmune condition should work closely with their healthcare providers to develop an individualized plan that supports both hormonal and immune balance. Staying informed, proactive, and engaged in one’s health can make a meaningful difference in managing symptoms and maintaining long-term well-being.
