Lupus and Gender – Top 10 Series

The following questions and answers are intended to help you better understand how lupus may present differently in men and women; however, you should always speak with your doctor about questions unique to your situation.

1. Lupus overview

Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease which affects multiple organ systems, resulting in tissue damage by autoantibodies (antibodies that attack healthy self-proteins). While many different parts of the body can be affected, SLE most often affects the skin, joints, and kidneys. The clinical manifestations of lupus are diverse, but common symptoms include fatigue, joint pain and swelling, fever, skin rash (“butterfly rash”), and sensitivity to light.

2. What is the male-to-female ratio of lupus patients?

The majority of lupus patients are female, with men comprising only 4% to 18% of those with the disease.1

The male-to-female ratio in lupus varies between different age groups. Among children and early adolescents, one in four patients diagnosed with SLE is male. Between the ages of 15 and 50, males represent approximately 6% to 10% of patients diagnosed with SLE. After the age of 50, the disparity drops slightly, as men comprise one in nine new cases.2

3. What is the mean age of onset of lupus in men versus women?

The mean age of disease onset for men is around 40, which is nearly ten years later than that for women.1 However, the diagnosis of lupus can be delayed in women – that is, it takes less time for men to be diagnosed with lupus once they present with symptoms.3 Lupus diagnosis after the age of 55 is termed “late onset lupus”; around 15% of patients with SLE will develop the disease later in life.4 When compared with SLE across all age groups, late onset lupus affects a higher percentage of men.

4. Why do so many more women have lupus than men?

While women comprise the majority of lupus patients across all age groups, the difference in rates of diagnosis by sex drops for pre-pubescent and post-menopausal age groups. The fact that rates of lupus diagnoses spike for women during their reproductive years suggests a possible link between certain sex hormones and SLE. Women with lupus have abnormally high levels of estrogen and low levels of progesterone5. In addition, some men with SLE may have lower levels of testosterone and higher levels of estrogen than men who do not have lupus.6

However, biological sex differences in immune function, especially those induced by sex hormones, are less likely explanations of sex differences. Recent studies suggest chromosomal basis and environmental exposure differences for the sex differences in the incidence of lupus.7

5. Are lupus disease manifestations markedly different between men and women?

While the clinical presentation of SLE in men is largely the same as that in women, based on a limited number of small scale studies, the manifestations listed below may be more common for men with lupus:

• Kidney problems7
• Seizures9
• Discoid rash (red, scaly and often circular in shape), as opposed to the malar rash, which often has a characteristic “butterfly” appearance10
• Increased risk of cardiovascular disease11
• Serositis (inflammation of tissues lining the lung, heart, and inner lining of the abdomen)12 and pleuritis (inflammation of the lining of the lungs)13
• Greater rate of hematologic involvement, including hemolytic anemia (anemia resulting from the destruction of red blood cells), lupus anticoagulant (which can promote abnormal clotting), lymphopenia (low white blood cell count), and thrombocytopenia (low platelet count).14

A study by Resende, et al. concluded that lupus nephritis may be more severe in men.15 In general, men may have more severe disease activity than women, however, large scale studies are needed to better define disease activity-related differences between men and women. It is important to keep in mind that the results of many of these studies are not conclusive, given the limited number of male patients participating in them.

6. Is lupus treatment different for men than for women?

In general, the treatment of lupus is not different for men and women. However, if the patient is a female of childbearing age, doctors often try to prescribe medications with limited teratogenic (birth defect causing) effects.

Drugs that women should avoid if trying to become – or are currently – pregnant include the following:

• cyclophosphamide (Cytoxan)
• methotrexate
• mycophenolate mofetil (CellCept)
• leflunomide (Arava)
• warfarin (Coumadin)16
• belimumab, rituximab, and anifrolumab

Similarly, male lupus patients on immunosuppressive medications (for example, methotrexate) should always have a detailed discussion with their physicians before considering pregnancy with their partners.

Each patient’s situation is unique and the course of treatment should be determined on an individual basis.

7. Are there reproductive issues faced by men and women with lupus?

Both men and women can experience reproductive problems related to their lupus diagnosis and treatment.

Women with lupus who become pregnant may experience disease flares, pregnancy loss, or other complications associated with high-risk pregnancies. While it is possible for women with lupus to have successful pregnancies, pregnant lupus patients are at a greater risk of preeclampsia (high blood pressure and excess protein in urine after 20 weeks of pregnancy), diabetes, urinary tract infections (UTIs), and preterm delivery.16

Certain lupus medications can be safely continued through pregnancy; others can cause harm to the fetus and must be avoided (see question 6). Learn more about pregnancy-related issues in lupus.

Male fertility is not thought to be directly affected by disease activity; rather, certain medications used to treat lupus have been shown to damage sperm producing cells. Studies have linked treatment with cyclophosphamide (Cytoxan) to an increased risk of infertility, in both men and women. It has also been found that men who are treated with glucocorticoid therapy may have reduced androgen levels.7

If you have concerns about the medications you are taking, it is always advisable to speak with your physician.

8. Is there a difference in cardiovascular disease risk for men and women?

Lupus patients are at an increased risk for cardiovascular events – such as heart attack or stroke – independent of the cardiovascular disease (CVD) risk factors (for example, hypertension, diabetes, smoking) to which much of the general population is susceptible.

Cardiovascular disease involves abnormal functioning of the heart and blood vessels (arteries and veins), which results in an increased risk of heart attack, heart failure, and stroke. Cardiovascular disease affects over half of all adults over the age of 607 and is a major cause of mortality in lupus patients.18

Amongst the general population, risk factors for CVD include hypertension, diabetes, and high cholesterol; certain behaviors, such as smoking, inactivity, and alcohol consumption may also contribute to a person’s risk of developing CVD. In lupus patients, active disease is also independent risk factor for cardiovascular events. Urowitz, et al. has found that men with lupus may have an increased risk of cardiovascular disease as compared with female patients.11

Learn more about CVD risk and prevention.

9. What are some emotional difficulties that men with lupus may face?

Men and women may experience different emotional difficulties when it comes to their diagnoses. In addition to the stress of a diagnosis, difficulty working and/or performing physical labor may be a source of emotional distress for male patients, given the social expectations of “maleness.”

While men with lupus are no less masculine than other men, male patients may have a difficult time with the traditional cultural association of SLE as a “woman’s disease.” Because SLE is prevalent in women to a much greater extent, it may be difficult for male patients to find other men with SLE as a means of support.

10. What can men do to help them cope with their lupus diagnosis?

Whether you are a man or a woman, it is important to discuss with family and friends how your diagnosis could impact your daily activities, and to include them in a discussion of how you plan to modify your lifestyle. The internet is a valuable resource for connecting with other male lupus patients. Online support groups and message boards can be helpful forums for sharing information and reaching out to other patients.

Read more about ways to cope with lupus.

Hospital for Special Surgery offers a number of patient support services. Patients can benefit from the Hospital’s programs – including a monthly SLE Workshop (organized by the Department of Social Work) – and counseling services.

Learn more about the Lupus and APS Center.

Updated: 9/13/2023

Authors

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References

1. Wallace DJ., Hahn BH (editors). Dubois’ Lupus Erythematosus. 6th edition. Philadelphia: Lippincott Williams & Wilkins, 2002.
2. Lahita RG. The Role of Sex Hormones in Systemic Lupus Erythematosus. Curr Opin Rhematol. 1999; 11(5):352-6.
3. Feng J., Ni J., Pan H., et al. Gender and Age Influence on Clinical and Laboratory Features in Chinese Patients with Systemic Lupus Erythematosus: 1,790 Cases. Rheumatol. Int. 2010; 30:1017-1023.
4. For Older Adults: Late Onset Lupus Fact Sheet. LUPUS Foundation of America, Inc. http://www.lupus.org/
5. Weckerle CE., Niewold TB. The Unexplained Female Predominance of Systemic Lupus Erythematosus: Clues from Genetic and Cytokine Studies. Clinical Reviews in Allergy and Immunology. 2011; 40:42-49.
6. Petri M. Review: Sex Hormones and Systemic Lupus Erythematosus. Lupus. 2008; 17:412-415.
7. Lockshin MD. Nonhormonal explanations for sex discrepancy in human illness. Ann N Y Acad Sci. 2010;1193:22-4.
8. Blum A., Rubinow A., Galun E. Predominance of Renal Involvement in Male Patients with Systemic Lupus Erythematosus. Clin Exp Rheumatol. 1991; 9:206-207.
9. Ward MM., Pyun E., Studenski S. Systemic Lupus Erythematosus in Men: A Multivariate Analysis of Gender Differences in Clinical Manifestations. J Rheumatol. 1990; 17:220-224.
10. Alekberova ZS., Folomeev MIu, Polyntsev IuV. The Role of Estrogen-Androgen Imbalance in Rheumatic Diseases [in Russian]. Ter Arkh. 1990; 62:17-21.
11. Urowitz M, et al. Atherosclerotic Vascular Events in a Multinational Inception Cohort of Systemic Lupus Erythematosus. Arthritis Care and Research. 2010; 62:881-887.
12. Miller MH., Urowitz MB., Gladmann DD., Killinger DW. Systemic Lupus Erythematosus in Males. Medicine. 1983; 62:327-334.
13. Camilleri F., Mallia C. Male SLE Patients in Malta. Adv Exp Med Biol. 1999; 455:173-179.
14. Kaufman LD., Gomez-Reino JJ., Heinicke MH., Gorevic PD. Male Lupus: Retrospective Analysis of the Clinical and Laboratory Features of 52 Patients, with a Review of the Literature. Semin Arthritis Rheum. 1989; 18:189-197
15. Resende AL., Titan SM., Barros RT., Woronik V. Worse Renal Outcome of Lupus Nephritis in Male Patients: A Case-Control Study. Lupus. 2011; 20(6):561-7.
16. Dwivedi AP., Erkan, D. Lupus and Pregnancy: Top Ten Points to Optimize the Outcome. Hospital for Special Surgery. 2010.
17. Basow DS (editor). Overview of the Risk Factors for Cardiovascular Disease. UpToDate. Waltham, 2011. www.uptodate.com/home/index.html.
18. Rusli M., Persad, P., Erkan, D. Lupus and Cardiovascular Disease (CVD) – Top Ten Points to Assess and Minimize Your Risk. Hospital for Special Surgery. 2010.

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