Anatomical and Hormonal Influences on Women's Dermatologic Health

Commentary

The Archives of Dermatology joins JAMA in dedicating its March issue to women's health¹ and, in doing so, commemorates the first International Women's Day, March 8, 1910.² In 1945, the Charter of the United Nations affirmed the principle of sexual equality.³ In 1995, the Beijing Conference and Platform for Action⁴ recognized that the empowerment of women is the most effective way to promote health, especially the prevention of human immunodeficiency virus (HIV) transmission and AIDS. Women usually visit their physicians more frequently than men do, take their children for care, and mediate health care for the family. Access to routine gynecologic and obstetric care helps women develop familiarity with the health care system and may contribute to women caring for others in the family and community.⁵

Some diseases may occur only or predominantly in women, including those affecting the genitalia or breast; other diseases are documented to be more prevalent in women. Dermatologic diseases are more likely to appear during certain decades of a woman's life, as shown in the table in our article⁵ in the March issue of the Archives of Dermatology. This commentary addresses the greater susceptibility of women to sexually transmitted diseases (STDs) and the greater prevalence of autoimmune diseases in women.

From a public health perspective, women's health concerns that span the life cycle include malnutrition in young girls, STDs in teenagers and young adult women, cervical and breast cancer in middle-aged women, and osteoporosis and potential bone fractures in older women. Sexually transmitted diseases can be transmitted through breaks in the mucous membranes that are exposed to infected bodily fluids.⁶ During sexual intercourse, women have more mucosal surface area exposed and more trauma to those tissues than men; therefore, women are at greater risk of contracting STDs from male partners.⁷ Women are exposed to higher concentrations of HIV present in semen compared with the concentration of HIV present in vaginal fluid.^{7 - 8} Millions of young individuals become sexually active each day, but have no access to prevention services.⁹ In sub-Saharan Africa, three quarters of all 15- to 24-year-olds living with HIV are female.⁹ As the article by Madkan et al¹⁰ in the March issue of Archives of Dermatology suggests, young women are 3 times more vulnerable to HIV infection than their male counterparts in part due to the use of sex as a bartering tool for money, food, and other basic necessities.

While infection of the genital area of men and women with different strains of human papillomavirus (HPV) is disfiguring and socially stigmatizing, most infections resolve without treatment, probably as a result of the development of an effective immunologic response.¹¹ Certain high-risk strains of the virus (HPV 16, HPV 18, HPV 31, or HPV 45) cause abnormal Papanicolaou test results in infected women and if the woman is exposed to other carcinogenic risks, these high-risk strains also may lead to cancer of the cervix, vulva, or anus. About 20 million US women and men are currently infected with HPV and about 5.5 million become newly infected each year.¹¹ The source of the infection is usually asymptomatic persons who do not realize they are infected.¹² Cervical cancer was predicted to cause 4000 deaths in the United States in 2004, with HPV identified as the main risk factor for the development of the disease.¹¹ Worldwide, more than 500 000 cases of cervical cancer will be diagnosed, accounting for 290 000 deaths among women per year.¹¹ Cultural and social norms, including education and financial status, strongly influence women's health care status. Women who are on the social and economic margins of some societies are often denied access to health care.⁵

Systemic lupus erythematosus (SLE) is among the diseases more prevalent in women than men, and is one of the most female-dominant of all autoimmune diseases. The sexually dimorphic prevalence of SLE, coupled with the dramatic increase in disease incidence in women after puberty, the reversal of this phenomenon after menopause, and the variation in disease severity throughout the menstrual cycle and pregnancy, prompted research of the role of sex hormones in the manifestations of autoimmune disease, as described by Ackerman¹³ in another article in the March issue of the Archives of Dermatology.

The acquired immune system of women differs from that of men because estrogens stimulate immunologic processes driven by CD4 T_H2 cells and B cells, whereas androgens enhance CD4 T_H1 and CD8 cell activity.¹⁴ Autoimmune diseases mediated by T_H2-dominant immunophysiological effects are proportionately more female-dominant than those conditions driven by T_H1-dominant activity.¹³ Patients with SLE demonstrate unique patterns of estrogen production and metabolism resulting in a 20-fold increase in the fraction of high-potency to low-potency estrogens in patients with SLE compared with healthy controls.¹⁵ High amounts of biologically potent estrogens cause patients with SLE to have more circulating self-reactive lymphocytes that bypassed developmental deletion, imbalanced proportions of lymphocytes favoring humoral responsiveness, and lymphocytes that are primed to react. Being primed to react does not mean a reaction will occur; autoreactive potential is unable to become more than potential without an inciting factor. Patients with SLE are immunoreactive because their lymphocytes are exposed to and stimulated by intracellular “self” components. Errant apoptosis permits exposure of self-antigens in patients with SLE. This errant apoptosis is fueled by estrogen, which increases Fas ligand expression and increases rates of monocyte apoptosis.¹⁶ The abundance of apoptotic material cannot be cleared and cellular necrosis occurs with the previously sequestered self-products now available for immunosurveillence.

The implications of understanding hormonal influences in patients with SLE are pharmacological manipulation to normalize the ratio of female to male sex hormones. Controlled trials investigated modification of SLE in women treated with 200 mg of dehydroepiandrosterone for 7 to 12 months, which reduced corticosteroid requirements and the frequency of disease flares, but resulted in acne and hirsutism in 35% and 10% of patients, respectively.¹⁷ In the future, hormonal manipulation may confer an advantage beyond corticosteroid sparing.