Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Anatomical and Hormonal Influences on Women's Dermatologic Health

Anatomical and Hormonal Influences on Women's Dermatologic Health Background Background Dermatological manifestations of sexually transmitted diseases (STDs) range from full body papulosquamous eruptions to genital ulcers and warts. The transmission, prevalence, and disease burden of STDs are not shared equally between the sexes. Observations Women are more susceptible than men for the acquisition of the human immunodeficiency virus and other dangerous STDs because of economic, biological, and social factors, and often sustain more damage to their health from the disease. Conclusion This review article elucidates the differential effect of STDs on women vs men to better understand what is required to protect women from the morbidity and mortality of STDs. Background Background The sexually dimorphic prevalence of autoimmune disease remains one of the most intriguing clinical observations among this group of disorders. While sex hormones have long been recognized for their roles in reproductive functions, within the past 2 decades scientists have found that sex hormones are integral signaling modulators of the mammalian immune system. Sex hormones have definitive roles in lymphocyte maturation, activation, and synthesis of antibodies and cytokines. Sex hormone expression is altered among patients with autoimmune disease, and this variation of expression contributes to immune dysregulation. Observations English-language literature from the last 10 years was reviewed to examine the relationship between sex hormones and the function of the mammalian immune system. Approximately 50 publications were included in this review, and the majority were controlled trials with investigator blinding that compared both male and female diseased and normal subjects. The review provided basic knowledge regarding the broad impact of sex hormones on the immune system and how abnormal sex hormone expression contributes to the development and maintenance of autoimmune phenomena, with a focus on systemic lupus erythematosus, as models of “lupus-prone” mice are readily available. Conclusions Sex hormones affect the function of the mammalian immune system, and sex hormone expression is different in patients with systemic lupus erythematosus than in healthy subjects. Sex hormones play a role in the genesis of autoimmunity. Future research may provide a therapeutic approach that is capable of altering disease pathogenesis, rather than targeting disease sequelae. 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. STDs: Anatomical Considerations for Prevalence 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 Autoimmune Diseases: Hormonal Reasons for Prevalence in Women 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 TH2 cells and B cells, whereas androgens enhance CD4 TH1 and CD8 cell activity.14 Autoimmune diseases mediated by TH2-dominant immunophysiological effects are proportionately more female-dominant than those conditions driven by TH1-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. Back to top Article Information Corresponding Author: June K. Robinson, MD, 132 E Delaware Pl, #5806, Chicago, IL 60611 (archdermatol@jama-archives.org). Financial Disclosures: None reported. Disclaimer: Dr Robinson was not involved in the editorial evaluation or editorial decision to accept this work for publication. References 1. DeAngelis CD, Glass RM. Women's health: a call for papers. JAMA. 2005;293:2662Google ScholarCrossref 2. History of International Women's Day: looking back. Available at: http://www.un.org/events/women/iwd/2005/history. Accessed December 12, 2005 3. Charter of the United Nations, 1945. Available at: http://www.un.org/aboutun/charter/. Accessibility verified February 21, 2006 4. Beijing Declaration and Platform for Action. Available at: http://www.un.org/womenwatch/daw/beijing/platform/index.html. Accessibility verified February 21, 2006 5. Robinson JK, Ramos-e-Siliva M. Women's dermatologic diseases, health care delivery, and socioeconomic barriers. Arch Dermatol. 2006;142:362-364Google ScholarCrossref 6. van Ginkel FW, Nguyen HH, McGhee JR. Vaccines for mucosal immunity to combat emerging infectious diseases. Emerg Infect Dis. 2000;6:123-13210756145Google ScholarCrossref 7. Ray SC, Quinn TC. Sex and the genetic diversity of HIV-1. Nat Med. 2000;6:23-2510613817Google ScholarCrossref 8. Pope M, Haase AT. Transmission, acute HIV-1 infection and the quest for strategies to prevent infection. Nat Med. 2003;9:847-85212835704Google ScholarCrossref 9. World Health Organization. UNAIDS/WHO AIDS Epidemic Update: Number of women living with HIV increases in each region of the world, December 2004. Available at: http://www.who.int/3by5/news34/en/. Accessed November 3, 2005 10. Madkan VK, Giancola AA, Sra KK, Tyring SK. Sex differences in the transmission, prevention, and disease manifestations of sexually transmitted diseases. Arch Dermatol. 2006;142:365-370Google ScholarCrossref 11. Gerberding JL.Centers for Disease Control and Prevention. Report to Congress: prevention of genital human papillomavirus infection, January 2004. Available at http://www.cdc.gov/std/HPV/STDFact-HPV.htm. Accessed November 3, 2005 12. Koutsky L. Epidemiology of genital human papillomavirus infection. Am J Med. 1997;102:(5A) 3-89217656Google ScholarCrossref 13. Ackerman LS. Sex hormones and the genesis of autoimmunity. Arch Dermatol. 2006;142:371-376Google ScholarCrossref 14. Beagley KW, Gockel CM. Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone. FEMS Immunol Med Microbiol. 2003;38:13-2212900050Google ScholarCrossref 15. Cutolo M. Estrogen metabolites: increasing evidence for their role in rheumatoid arthritis and systemic lupus erythematosus. J Rheumatol. 2004;31:419-421Google Scholar 16. Mor G, Sapi E, Abrahams V. et al. Interaction of the estrogen receptors with Fas ligand promoter in human monocytes. J Immunol. 2003;170:114-12212496390Google Scholar 17. van Vollenhoven RF. Dehydroepiandrosterone for the treatment of systemic lupus erythematosus. Expert Opin Pharmacother. 2002;3:23-31Google ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Anatomical and Hormonal Influences on Women's Dermatologic Health

Robinson, June K.
JAMA , Volume 295 (12) – Mar 22, 2006
Download PDF
3 pages

Loading next page...
 
/lp/american-medical-association/anatomical-and-hormonal-influences-on-women-s-dermatologic-health-3T1vdhNe7i

References (17)

Publisher
American Medical Association
Copyright
Copyright © 2006 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.295.12.1443
Publisher site
See Article on Publisher Site

Abstract

Background Background Dermatological manifestations of sexually transmitted diseases (STDs) range from full body papulosquamous eruptions to genital ulcers and warts. The transmission, prevalence, and disease burden of STDs are not shared equally between the sexes. Observations Women are more susceptible than men for the acquisition of the human immunodeficiency virus and other dangerous STDs because of economic, biological, and social factors, and often sustain more damage to their health from the disease. Conclusion This review article elucidates the differential effect of STDs on women vs men to better understand what is required to protect women from the morbidity and mortality of STDs. Background Background The sexually dimorphic prevalence of autoimmune disease remains one of the most intriguing clinical observations among this group of disorders. While sex hormones have long been recognized for their roles in reproductive functions, within the past 2 decades scientists have found that sex hormones are integral signaling modulators of the mammalian immune system. Sex hormones have definitive roles in lymphocyte maturation, activation, and synthesis of antibodies and cytokines. Sex hormone expression is altered among patients with autoimmune disease, and this variation of expression contributes to immune dysregulation. Observations English-language literature from the last 10 years was reviewed to examine the relationship between sex hormones and the function of the mammalian immune system. Approximately 50 publications were included in this review, and the majority were controlled trials with investigator blinding that compared both male and female diseased and normal subjects. The review provided basic knowledge regarding the broad impact of sex hormones on the immune system and how abnormal sex hormone expression contributes to the development and maintenance of autoimmune phenomena, with a focus on systemic lupus erythematosus, as models of “lupus-prone” mice are readily available. Conclusions Sex hormones affect the function of the mammalian immune system, and sex hormone expression is different in patients with systemic lupus erythematosus than in healthy subjects. Sex hormones play a role in the genesis of autoimmunity. Future research may provide a therapeutic approach that is capable of altering disease pathogenesis, rather than targeting disease sequelae. 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. STDs: Anatomical Considerations for Prevalence 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 Autoimmune Diseases: Hormonal Reasons for Prevalence in Women 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 TH2 cells and B cells, whereas androgens enhance CD4 TH1 and CD8 cell activity.14 Autoimmune diseases mediated by TH2-dominant immunophysiological effects are proportionately more female-dominant than those conditions driven by TH1-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. Back to top Article Information Corresponding Author: June K. Robinson, MD, 132 E Delaware Pl, #5806, Chicago, IL 60611 (archdermatol@jama-archives.org). Financial Disclosures: None reported. Disclaimer: Dr Robinson was not involved in the editorial evaluation or editorial decision to accept this work for publication. References 1. DeAngelis CD, Glass RM. Women's health: a call for papers. JAMA. 2005;293:2662Google ScholarCrossref 2. History of International Women's Day: looking back. Available at: http://www.un.org/events/women/iwd/2005/history. Accessed December 12, 2005 3. Charter of the United Nations, 1945. Available at: http://www.un.org/aboutun/charter/. Accessibility verified February 21, 2006 4. Beijing Declaration and Platform for Action. Available at: http://www.un.org/womenwatch/daw/beijing/platform/index.html. Accessibility verified February 21, 2006 5. Robinson JK, Ramos-e-Siliva M. Women's dermatologic diseases, health care delivery, and socioeconomic barriers. Arch Dermatol. 2006;142:362-364Google ScholarCrossref 6. van Ginkel FW, Nguyen HH, McGhee JR. Vaccines for mucosal immunity to combat emerging infectious diseases. Emerg Infect Dis. 2000;6:123-13210756145Google ScholarCrossref 7. Ray SC, Quinn TC. Sex and the genetic diversity of HIV-1. Nat Med. 2000;6:23-2510613817Google ScholarCrossref 8. Pope M, Haase AT. Transmission, acute HIV-1 infection and the quest for strategies to prevent infection. Nat Med. 2003;9:847-85212835704Google ScholarCrossref 9. World Health Organization. UNAIDS/WHO AIDS Epidemic Update: Number of women living with HIV increases in each region of the world, December 2004. Available at: http://www.who.int/3by5/news34/en/. Accessed November 3, 2005 10. Madkan VK, Giancola AA, Sra KK, Tyring SK. Sex differences in the transmission, prevention, and disease manifestations of sexually transmitted diseases. Arch Dermatol. 2006;142:365-370Google ScholarCrossref 11. Gerberding JL.Centers for Disease Control and Prevention. Report to Congress: prevention of genital human papillomavirus infection, January 2004. Available at http://www.cdc.gov/std/HPV/STDFact-HPV.htm. Accessed November 3, 2005 12. Koutsky L. Epidemiology of genital human papillomavirus infection. Am J Med. 1997;102:(5A) 3-89217656Google ScholarCrossref 13. Ackerman LS. Sex hormones and the genesis of autoimmunity. Arch Dermatol. 2006;142:371-376Google ScholarCrossref 14. Beagley KW, Gockel CM. Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone. FEMS Immunol Med Microbiol. 2003;38:13-2212900050Google ScholarCrossref 15. Cutolo M. Estrogen metabolites: increasing evidence for their role in rheumatoid arthritis and systemic lupus erythematosus. J Rheumatol. 2004;31:419-421Google Scholar 16. Mor G, Sapi E, Abrahams V. et al. Interaction of the estrogen receptors with Fas ligand promoter in human monocytes. J Immunol. 2003;170:114-12212496390Google Scholar 17. van Vollenhoven RF. Dehydroepiandrosterone for the treatment of systemic lupus erythematosus. Expert Opin Pharmacother. 2002;3:23-31Google ScholarCrossref

Journal

JAMA – American Medical Association

Published: Mar 22, 2006

There are no references for this article.