The International Pemphigus & Pemphigoid Foundation and Dr. Sarah Brenner recently conducted a survey on some aspects of pemphigus, in particular the gender distribution of the patients, and the relationship between the disease and the use of sex hormones.
A total of 249 members of the Foundation answered a short questionnaire on their gender, the age at which they developed the disease, and whether they were taking hormones when it began. There were 151 women and 91 men, a female:male ratio of 1.7:1.
Is there indeed a predominance of women among pemphigus patients? Or are women simply more responsive to questionnaires?
If these numbers do reflect a female predominance, we would like to address the possible reasons. A major factor is the involvement of the immune system in the course of the disease that makes women more susceptible to this and other autoimmune disorders. Sex steroids affect how the immune system develops and functions differently in men and women. The currently held view is that androgens, the male hormones, are anti-inflammatory and depress immunity, while estrogens, the female hormones, enhance it. The result is that women have a greater immune response to external agents. It is known, for instance, that females are more prone to develop autoimmune diseases like systemic lupus erythematosus (SLE) and multiple sclerosis, while males tend to develop lupus later in life or due to disturbed hormonal regulation. Indeed, more than 75% of patients with autoimmune diseases are women. Thus, it is clear that hormonal make-up renders women more likely to develop pemphigus than men.
A second factor in the preponderance of women among pemphigus patients is the strikingly high proportion of users of hormone replacement therapy (HRT) found among postmenopausal women. In the survey, 20 of the 43 postmenopausal women were on HRT at the time they developed the disease. The immune system of women is exposed to estrogens in a number of ways, some internal like the natural estrogenic hormones produced in conditions such as pregnancy. But, estrogenic hormones can enter the body from outside as well, for medical reasons like replacement therapy and contraception, or via environmental agents such as plastics, pesticides, plants, and the like.
Almost every second woman after menopause in the survey was consuming some form of sex hormone. This finding is higher than the 30% figure for hormone replacement therapy documented in a 2001 study of all adult women in the United States and the United Kingdom1. Do these figures argue for the role of hormone supplements in the disease?
Another interesting finding is the use of hormonal supplements in 4 out of the 91 men in the survey. The purpose of this hormone intake by men is unknown and has not been addressed in the medical literature. Epidemiological studies are needed to assess the extent of this phenomenon among men, but one can speculate on a trend of treatments for male menopause (andromenopausa) or anti-aging. Does testosterone intake play a role in pemphigus? This finding merits further study.
We wish to express our special thanks to Janet D. Segall, Interim Executive Director and Director of Patient Services, and Will Zrnchik, Director of Development and Communications, of the International Pemphigus & Pemphigoid Foundation for conducting the survey discussed here. We would like to thank all those who answered the survey, and look forward to more such service in the future.
by Sarah Brenner, M.D. Dermatology
Tel Aviv-Sourasky Medical Center, and Tel Aviv University Sackler School of Medicine
1. Coombs JN, Taylor R, Wilcken N, Fiorica J, Boyages J. Hormone replacement therapy and breast cancer risk in California. Breast J. 2005;11:410-415.