The Role of Hormones in Lupus: Why It’s More Common in Women

Lupus, particularly Systemic Lupus Erythematosus (SLE), is an autoimmune disease that disproportionately affects women. In fact, approximately 90% of lupus cases occur in females, especially during their reproductive years. 

This rather extreme gender imbalance suggests that hormonal factors, particularly estrogen, play a key role in lupus development.

While there are four recognized types of lupus, this article will focus on the overwhelmingly increased incidence of SLE in women by exploring the relationship between hormones and lupus. 

The aim is to increase awareness about how hormonal fluctuations influence disease activity and provide relevant insights for clinicians managing lupus in female patients.

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What is Lupus? A Brief Overview

Lupus is a chronic, complex autoimmune disease in which the body’s immune system mistakenly attacks healthy tissues, causing inflammation in various organs including (but not limited to) the skin, joints, kidneys, and heart. 

This overactive immune response leads to a range of symptoms, and if untreated, it can develop into complications that vary from mild to life-threatening.

There are four recognized types of Lupus:

• Systemic Lupus Erythematosus (SLE): the most common and severe form of lupus, affecting multiple organ systems.

• Cutaneous Lupus: primarily affects the skin, often resulting in rashes or lesions, especially in sun-exposed areas. Cutaneous lupus encompasses acute, subacute, or chronic (discoid) lupus erythematosus.

• Drug-Induced Lupus: a temporary lupus-like condition triggered by certain medications, which usually resolves after discontinuing the medication.

• Neonatal Lupus: a rare form that affects newborns, usually caused by antibodies passed from the mother.

General Symptoms and Complications of Systemic Lupus Erythematosus (SLE)

The diverse symptoms of lupus can make diagnosis challenging for clinicians. Common symptoms include:

• Fatigue

• Joint pain and swelling

• Skin rashes, especially on sun-exposed areas

• Fever

• Photosensitivity

• Hair loss

• Oral ulcers

• Kidney problems (lupus nephritis)

• Neurological symptoms, such as seizures or memory loss

• Eye problems 

Because lupus symptoms can overlap with other autoimmune conditions, identifying risk factors is necessary for an accurate and timely diagnosis.

Left untreated, many complications can develop. Common and serious complications of SLE include:

• Lupus nephritis, a kidney inflammation that can lead to kidney failure if not adequately treated. 

• Heart and lung problems like inflammation of the heart lining (pericarditis), inflammation of the lung lining (pleuritis), and blood clots and high blood pressure in the lungs (pulmonary embolism and pulmonary hypertension).

• It can also lead to brain and nerve issues like seizures, mental confusion, or strokes that affect the brain.

• Additionally, lupus can affect the blood, causing conditions like anemia (low red blood cells), leukopenia (low white blood cells), and thrombocytopenia (low platelet count).

Lupus and Hormonal Differences in Women: Why is Lupus More Common in Women?

Lupus is overwhelmingly more common in women than in men, which likely involves the interplay between a woman’s hormones and immune system function.

Why Lupus is More Common in Women

Higher Estrogen Levels

Women generally have higher levels of estrogen, particularly during their reproductive years, which alters immune system activity and contributes to the onset or exacerbation of lupus.

Hormonal Fluctuations

Life events such as puberty, pregnancy, and menopause significantly affect estrogen levels, and these fluctuations can trigger lupus flare-ups. For example, many women experience lupus onset or worsening during puberty or pregnancy when estrogen surges.

Immune System Differences

Women’s immune systems are inherently more active than men’s, providing greater protection against infections but also increasing the risk of autoimmune diseases like lupus.

The Influence of Estrogen on Lupus

Estrogen’s influence on lupus is due to estrogen’s effects on immune system balance. 

Here’s how estrogen impacts lupus progression:

Estrogen’s Role in Immune Balance and Autoimmunity

Estrogen, especially its strongest form estradiol, stimulates the immune system. It promotes inflammation and boosts the production of autoantibodies—antibody proteins that mistakenly attack the body’s own tissues. 

This is the overactive immune response that causes widespread damage characteristic of lupus. 

For example, estrogen acts on immune cells through special estrogen receptors (ER-α and ER-β) that push the immune system to produce more antibodies like anti-double stranded DNA (anti-dsDNA), which is a key marker of lupus.

Normally, the immune system has regulatory T cells (T-regs) that help prevent autoimmunity. However, in people with lupus, estrogen reduces the effectiveness of T-regs, making it harder for the immune system to control itself. 

This breakdown in immune regulation, along with increased antibody production, are major factors in lupus flare-ups and disease progression.

How Estrogen Fluctuations Trigger Lupus Flares

Hormonal changes, like those during pregnancy or the menstrual cycle, can worsen lupus symptoms. 

Rising estrogen levels, especially in pregnancy, boost inflammation and immune system activity. Women with lupus may experience flares that sync with their menstrual cycle, likely due to estrogen fluctuations. 

Additionally, lupus patients often have higher estrogen metabolites and lower progesterone, so they lose progesterone’s immune-regulating benefits. 

Finally, the genetic makeup of women, including having two X chromosomes, also raises lupus risk; specific genes that affect estrogen response likely contribute to why women are more affected than men.

Common Lupus Symptoms in Women

Hormonal influences can cause lupus symptoms to look different in women than in men.

Lupus Symptoms More Commonly Seen in Women

Women with lupus commonly experience fatigue, joint pain, and skin rashes, but these symptoms can be more pronounced or triggered by hormonal changes. 

Lupus can also flare during menstruation, pregnancy, and menopause, further affecting a woman’s quality of life.

Hormonal Triggers

Menstrual Cycle

Many women report that lupus symptoms, such as joint pain and fatigue, worsen before or during their menstrual periods.

Pregnancy

The immune and hormone changes during pregnancy, particularly increased estrogen levels, can exacerbate lupus symptoms.

During Menopause

Estrogen levels decrease during menopause, which can lead to fewer lupus flares in some women. 

However, hormone replacement therapy (HRT), commonly prescribed to manage menopausal symptoms, may potentially trigger lupus activity. Women with lupus who are considering HRT should consult with their healthcare providers to assess the risks and benefits.

How Symptoms Differ from Men

While fatigue and joint pain are common in both men and women with lupus, women may have more severe skin involvement, including skin rashes, sensitivity to sunlight, and hair loss, as well as being more likely to experience hormone-related complications. 

Men with lupus tend to have more severe organ involvement, such as kidney and heart complications, as well as more severe neuropsychiatric complications.

Case Studies: Women and Lupus

The following case studies are examples of how lupus can manifest in women.

20 Year Old Woman With Bone Pain

A 20-year-old woman experienced fatigue, severe anemia (low red blood cell count), shortness of breath, and bone pain. 

Initially, her anemia worsened, and she also developed low white blood cells alongside heavy periods, but no common lupus symptoms like rashes or joint swelling emerged. 

She was first diagnosed with autoimmune myelofibrosis (scarring of the bone marrow) and later with systemic lupus erythematosus (SLE). 

Treatment with corticosteroids (reduce inflammation) and Plaquenil (an immune modulator) improved her condition. 

Hormonal factors, like estrogen fluctuations during her menstrual cycle, likely worsened her symptoms. 

25 Year Old Woman with Heart Failure

A 25-year-old woman came to the doctor with extreme fatigue, weight loss, trouble breathing (dyspnea), fever, chest and abdominal pain, and hair loss. 

Over two months her symptoms worsened, leading to anemia, low white blood cells (leukopenia), and a serious condition called pericardial effusion, which caused cardiac tamponade (life-threatening pressure on the heart). 

After having fluid drained from around her heart (pericardiocentesis), she developed an abdominal infection called peritonitis. 

Blood tests confirmed lupus (SLE). Treatment with steroids, Plaquenil (hydroxychloroquine, which alters immune system activity), and azathioprine (an immunosuppressant) improved her condition.

26 Year Old Pregnant Woman with Lupus Flare

This case involves a 26-year-old pregnant woman with lupus who experienced a severe flare. 

She initially presented with a rash, hair loss, and worsening kidney issues, later diagnosed as lupus nephritis (kidney inflammation caused by lupus). She also faced a risk of fetal heart block, a condition where electrical signals to the baby’s heart slow or stop. 

Medications like corticosteroids (to reduce inflammation), hydroxychloroquine (for immune system regulation), and azathioprine (an immunosuppressant) helped manage her condition. 

Despite complications, she delivered a healthy baby and improved with continued treatment.

Treatment Approaches Considering Hormonal Influences

Treatment approaches for women with lupus must consider the interactions between the immune system and her hormones.

Hormone Therapy

Hormone replacement therapy (HRT) can help alleviate menopausal symptoms but may worsen lupus in some women. The decision to use HRT in women with lupus should be individualized, balancing the potential benefits with the risks of triggering disease flares.

Medications for Lupus

Steroids and Immunosuppressants 

Medications like corticosteroids and immunosuppressive drugs are commonly used to control lupus inflammation. However, hormonal changes can influence the effectiveness of these treatments, which may necessitate dose adjustments during pregnancy or menopause.

Biologics

Biologic medications are a type of treatment that targets specific parts of the immune system to reduce inflammation and prevent organ damage in lupus. 

Examples include belimumab, which works by reducing antibody production, and anifrolumab, which blocks chemical messenger pathways in the immune system. These biologics are especially helpful for patients with non-renal lupus who don't respond well to traditional treatments by providing targeted options to manage severe symptoms.

Lifestyle Changes

Managing lupus symptoms through lifestyle changes can help balance hormones and reduce flare-ups. 

A healthy diet, regular exercise, and stress management are essential strategies. For instance, maintaining a balanced diet rich in anti-inflammatory foods can help regulate hormones and mitigate lupus symptoms. 

Stress reduction techniques such as mindfulness and yoga can also positively affect hormone levels and immune function.

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Key Takeaways

• Hormones and Lupus Prevalence: hormonal fluctuations, particularly involving estrogen, significantly contribute to the higher prevalence and severity of lupus in women, especially during their reproductive years.

• Increasing Clinical Awareness: recognizing the role of hormones and early symptoms like joint pain and fatigue is foundational for diagnosing lupus early and improving outcomes in women.

• Treatment Adjustments: hormonal changes, such as those during pregnancy or menopause, may require adjustments in lupus treatment to better manage symptoms and reduce flare-ups.