Perimenopause & Beyond
Autoimmune and rheumatological diseases occur more frequently in women, likely due to the influence of sex hormones on the immune system's development and function, especially noticeable during pregnancy. Oestrogens, in particular, play a key role in modulating the immune response, as their receptors are found in almost all immune cells, where they control the expression of genes related to inflammation. So, is there a link between autoimmune disease and menopause? There is limited information on the impact of menopause on autoimmune diseases, even though evidence suggests that hormonal changes during menopause may trigger the onset of autoimmune conditions or modify the progression of existing diseases.
The reduction of oestrogens can also contribute to "inflammaging," a pro-inflammatory state linked with aging that is involved in the development of degenerative conditions like osteoarthritis. It has been demonstrated that alterations or loss of sex hormones—whether natural, autoimmune, pharmacological, or surgical—directly affect susceptibility to musculoskeletal pain, which can be partially improved and alleviated by hormone replacement therapy.
Women are generally more impacted by autoimmune diseases than men, with notably high female-to-male ratios in connective tissue diseases: 9:1 for systemic lupus erythematosus (SLE) and Sjogren’s syndrome, and 3:1 for systemic sclerosis. Epidemiological data indicate that while autoimmune diseases are more prevalent in women, the occurrence and progression of various rheumatic diseases differ across reproductive stages, reflecting hormonal changes. Menopause appears to be a pivotal point in the relationship between age and immune function.
The menopause may trigger the development of autoimmune rheumatic diseases; the most studied and described is RA, which is often diagnosed within a few years before or after menopause. In addition to the systemic effects, oestrogens may also play a significant role in local inflammation within tissues. A later menopause has been associated with a lower risk of developing RA, further suggesting a protective role of oestrogens for the onset of disease. It has been suggested that the early menopause may induce RA onset and worsen RA symptoms, possibly due to the loss of the oestrogen immunomodulatory effects.
This table summarises some autoimmune diseases that can be triggered or unmasked around menopause
Autoimmune Disease | Typical Onset Age (esp. post-menopause) | Hallmark Symptoms |
Rheumatoid Arthritis (RA) | 45–65 years | Symmetric joint pain & swelling (esp. hands, wrists), morning stiffness >1 hr, fatigue |
Systemic Lupus Erythematosus (SLE) | Often 30–50, but flares or first onset possible post-menopause | Fatigue, joint pain, photosensitive rash, oral ulcers, serositis, possible kidney involvement |
Sjögren’s Syndrome | 45–60 years | Dry eyes (gritty feeling), dry mouth, dental caries, fatigue, arthralgias |
Hashimoto’s Thyroiditis | Peak at 45–65 years | Fatigue, weight gain, cold intolerance, constipation, dry skin, goitre |
Graves’ Disease | 40–60 years | Weight loss, heat intolerance, tremor, palpitations, goitre, eye changes (exophthalmos) |
Primary Biliary Cholangitis (PBC) | 50–65 years | Fatigue, pruritus, jaundice (late), hepatomegaly |
Multiple Sclerosis (MS) | Most common at 20–40, but late onset 50–60 possible | Numbness, weakness, visual changes, imbalance, bladder issues |
Psoriatic Arthritis | 40–60 years | Joint pain/swelling with psoriasis skin lesions, nail pitting |
Coeliac Disease | Can present at any age; sometimes first at 40–60 | Chronic diarrhoea, bloating, iron-deficiency anaemia, weight loss |
Autoimmune Hepatitis | 40–60 years | Fatigue, jaundice, right upper quadrant discomfort |
The causes of autoimmune diseases are complex and include genetic, environmental, hormonal, and immunological factors, all of which are considered significant in their development. Most autoimmune disorders arise from unknown causes. Numerous retrospective studies have found that up to 80% of patients experienced unusual emotional stress before the onset of the disease. Recent reviews explore the potential role of psychological stress and major stress-related hormones in the development of autoimmune diseases. It is believed that stress-induced hormones cause immune dysregulation, ultimately leading to autoimmune diseases. Therefore, treating autoimmune diseases should involve stress management and behavioural interventions to prevent stress-related immune imbalances. And prioritising stress management at perimenopause and beyond may further prevent the onset or reduce severity of autoimmune flares.
