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Sexx Matters

Sexually Transmitted Infections in Women: An Overview

Viviana Simon, PhD; Jennifer Wider, MD

The epidemiologic implications of sexually transmitted infections (STIs) in women are alarming—but for physicians willing to accept the challenge, preventive efforts can turn the tide one patient at a time.

Sexually transmitted infections are preventable, yet the incidence is increasing—especially among adolescents, women, and minorities. Today, STIs affect more than 19 million Americans annually, nearly 50% of whom are younger than age 25 years.1,2 Infections can be bacterial (eg, chlamydia, gonorrhea, syphilis), viral (eg, human immunodeficiency virus [HIV], herpes simplex virus [HSV], hepatitis, human papillomavirus [HPV]), or parasitic (eg, trichomoniasis). Infections caused by bacteria are curable with antibiotics, whereas some viral infections are only treatable. The consequences of infection range from mild, acute illness to serious, long-term complications. The annual cost of STIs in the United States has been estimated at $17 billion.3

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gENDER DIFFERENCES

Incidence

With regard to three major STIs—chlamydia, gonorrhea, and syphilis—chlamydia infections rose steadily between 1984 and 2003, while gonorrhea infections declined.1 In 2003, the chlamydia rate was 3-fold higher in women than in men, and the gonorrhea rate was slightly higher in women. By contrast, the rate of syphilis infection increased in men and decreased in women during the same period.1

Women are now also the leading group affected by HIV, accounting for 33% of all new US infections. In 2003, black and Hispanic women represented 83% of female acquired immunodeficiency syndrome (AIDS) diagnoses. Heterosexual contact is the source of more than 80% of female HIV infections.4 An important determinant of this disparity is womenÍs lack of perceived risk—particularly minority women who may not be aware of their male partnersÍ bisexuality or multiple partners.5 Young women currently account for 64% of all new HIV infections among people aged 13 to 19 years.6

Vulnerability

The risk of infection during unprotected intercourse is 2-fold to 4-fold higher in women.7,8 Contributing factors include greater surface area exposed during intercourse, the higher viral load in semen than in vaginal fluids, and microabrasions occurring in the vaginal epithelium during sex. Adolescent women are particularly vulnerable because their cervical tissues are more readily penetrated by infectious organisms.9 Moreover, menstrual hormone fluctuations and the use of oral contraceptives (OCs) can cause cervical ectopy and changes in the genital mucosa and vaginal pH.10 Also, postmenopausal women and those who use OCs have thinner cervical mucus, and are more likely to sustain abrasions.

As many STIs are asymptomatic, women of reproductive age must be tested routinely. Maternal transmission of infections can occur before, during, or after birth. Syphilis can cross the placenta, while gonorrhea, chlamydia, hepatitis Β, and HSV can be transmitted during delivery. Notably, HIV can be transmitted at any point during pregnancy and birth, and (unlike most STIs) during breast-feeding.11-13

Vulnerability to STIs is compounded for both sexes by coinfection with other STIs.14 For example, HIV-positive women with severe immunosuppression are more likely to contract HPV and go on to develop cervical cancer.15 Ulcerative STIs (eg, HSV) cause sores from which the virus can be released, and syphilitic ulcers increase susceptibility of HIV. Transmission of STIs can also occur from an infected partner who has no visible sores.

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CASE REPORTING

Although 71% of STI cases are treated in private practice, private physicians rarely screen for the most common STIs—including HIV. It has been shown that men, nonpregnant women, and pregnant women were screened 12% to 24%, 20% to 35%, and 30% to 32% of the time, respectively—ie, below clinical prevention guidelines.16-18 In addition, many private physicians were unsure of the reporting requirements of their states, and/or who was ultimately responsible for reporting.16,19

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DIAGNOSIS AND TREATMENT

Chlamydia

Patients with chlamydia are usually asymptomatic and do not seek medical attention, but are still at risk for transmission and complications. For women, chlamydia can lead to pelvic inflammatory disease (PID), in turn raising the risk of chronic pelvic pain by 18%, ectopic pregnancy by 15%, and tubal occlusion/infertility by 12% to 50%.20-24

The US Centers for Disease Control and Prevention recommends screening all women under age 20 years during routine annual gynecologic examinations, and women over age 20 years who are noncompliant with barrier contraception or who had multiple sexual partners during the previous 3 months. It is especially important to screen pregnant women because gestational infection is associated with preterm contractions and rupture of membranes, low birthweight, and fetal/infant eye damage, pneumonia, and mortality.1,25,26 Culturing has been largely replaced by DNA/RNA amplification.27 Antibiotics used in nonpregnant women include azithromycin, doxycycline, or erythromycin base. Pregnant women can be treated with amoxicillin, azithromycin, or erythromycin base. A single oral dose of azithromycin is highly effective and well tolerated.28

Gonorrhea

Gonorrhea is the second most commonly reported notifiable disease in the United States, and can also cause PID, infertility, and chronic pelvic pain.1,23 Symptoms include burning during urination, frequent urination, and genital pruritus, erythema, and edema. However, more than 50% of infections in women are asymptomatic. It is estimated that approximately 1 million US women are currently infected, of whom 25% to 40% also have chlamydia.29,30 Unless a negative chlamydia diagnosis is available, patients with gonorrhea should also be treated for chlamydia.18

Women tend to acquire gonorrhea at an earlier age than men, and have higher rates of infection between ages 10 and 19 years.1 Incidence varies greatly by race, age, geographic area, and sex.29 In 2003, rates of infection in all but eight states were at least 6-fold higher than the national target of 19 per 100,000.31 The highest rates occurred in black women aged 15 to 24 years and black men aged 20 to 24 years. Selected US cities accounted for over 44.1% of all cases.1

Drug-resistant gonorrhea strains have increased dramatically during the past 20 years; 16.4% of isolates collected in 2003 were resistant to penicillin, tetracycline, or both.32-34 Cefixime, ceftriaxone, ciprofloxacin, levofloxacin, and ofloxacin are highly effective as single-dose therapies; if cotreating for chlamydia, azithromycin as a single dose or doxycycline twice daily for 7 days is recommended.18

Syphilis

Syphilis is initially characterized by a chancre at the infection site, while second-stage symptoms are nonspecific (eg, rashes, fever, headaches, sore throat, patchy hair loss, muscle aches, fatigue).1 Syphilis during pregnancy can result in spontaneous abortion, stillbirth, intrauterine growth restriction, premature delivery, and perinatal death. Failure to treat an infected infant can lead to severe developmental delays and death.35 Simple screening procedures during the first and the third trimester can significantly reduce congenital transmission. Common screens include the Venereal Disease Research Laboratory and rapid plasma reagin tests, with confirmation via the fluorescent treponemal antibody absorbed or Treponema pallidum particle agglutination tests. Treatment employs benzathine penicillin G, with the regimen depending on the disease stage.

Although the rates of syphilis are much lower than those of other STIs, it continues to be a problem among minority populations and homosexual/bisexual men. While 88% of reporting counties (2,530/3,140) were syphilis-free, only three of 63 selected large cities had rates below the national target of 0.2/100,000.18

Human Immunodeficiency Virus

In 2001, HIV was the fourth leading cause of death for US women aged 35 to 44 years, and the sixth leading cause of death for women aged 25 to 34 years.36,37 And while black and Hispanic women represent approximately 25% of the US female population, they accounted for 83% of AIDS cases reported in 2003.37

During unprotected heterosexual intercourse, women have a greater risk of HIV infection than men.37 Other STIs may act as cofactors for HIV transmission and vice versa. This is especially relevant for women, who are at higher risk of contracting STIs at a single exposure. Both ulcerative STIs (eg, HPV, syphilis, chancroid) and nonulcerative STIs (eg, chlamydia) enhance susceptibility to HIV. Variations in vaginal pH and flora may also be contributing factors.

While some studies have found a lower viral load in women than men at the same median CD4/T cell counts, others found no difference.38-42 This gender difference is likely present early in the infection, and diminishes or disappears within 4 to 5 years of seroconversion.43,44 Progression to AIDS is the same for men and women, but women may progress to AIDS at a lower viral dose. Regardless of viral load, both men and women should consider taking anti-HIV drugs if their T cell counts are below 350 cells/mm3. Studies have shown that viral loads fluctuate with the menstrual cycle, which can affect the risk of HIV transmission.45,46

There are several regimens of combination drug treatment with protease inhibitors and nucleotide or nonnucleotide reverse trans-criptase inhibitors.44 Few studies have compared drug effectiveness, pharmacokinetics, and adverse effects in women versus men. Nevirapine has been evaluated in preventing mother-to-child transmission of the virus, but women are twice as likely as men to experience elevation of liver enzymes during the first 4 weeks of use.47

Human Papillomavirus

Approximately 80% of sexually active individuals will contract HPV.48 In the United States, HPV is the most common STI. There are more than 100 types of HPV, but only about 30 are sexually transmitted. Some types (eg, HPV 6, 11) cause condyloma acuminata, but genital infection can occur without warts. Other types (eg, HPV 16, 18, 31, 33, 35) have been strongly associated with cervical neoplasia and cancer.

The primary goal of treating visible genital warts is removal. In most patients, treatment can induce wart-free periods. If left untreated, visible genital warts may resolve, remain unchanged, or worsen. Therapy may reduce infectivity but probably does not eradicate it. Treatment options include podofilox 0.5% solution/gel, imiquimod 5% cream, cryotherapy, podophyllin resin 10% to 25%, trichloroacetic acid, bichloroacetic acid 80% to 90%, or surgical removal.18

Infection with a high-risk HPV strain increases the risk of cervical cancer by 200-fold.49 Regular Papanicolaou (Pap) smears are recommended for women of reproductive age, and can reduce the number of cervical cancer cases by 75%.50 Adding an HPV DNA test increases the ability to identify women at risk to between 93% and 100%. Guidelines recommend yearly Pap tests for women under age 30 years beginning within 3 years of first intercourse. For women over age 30 years, combination Pap and HPV DNA testing is recommended every 3 years.

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CONCLUSION

The Institute of Medicine has recommended creating a national system for STI prevention.3 Physicians must not only be well-informed about sexual health issues, but must also become more comfortable discussing these issues with their patients. Strategies include early identification of infected individuals and high-risk populations, adequate treatment of patients and their partners, modification of high-risk behavior, and promotion of health care accessibility and use. Both abstinence and condom use must be addressed. Messages should be culturally and age-relevant, embracing the concept of lifelong sexual health. Finally, physicians should strive to stimulate discussions about sexual health in their patientsÍ homes, and throughout their communities.

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Viviana Simon, PhD, is director, scientific programs; and Jennifer Wider, MD, is medical advisor. Both are at the Society for WomenÍs Health Research, Washington, DC.

References

1. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2003. Atlanta, Ga: US Department of Health and Human Services; 2004.
2. National Institute of Allergy and Infectious Diseases. Health Matters: An Introduction to Sexually Transmitted Infections. Bethesda, Md: National Institutes of Health, US Department of Health and Human Services; 1999.
3. Eng TR, Butler WT, eds. The Hidden Epidemic: Confronting Sexually Transmitted Diseases. Washington, DC: National Academy Press; 1997.
4. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report, 2003. Vol. 15. Atlanta, Ga: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2004. Available at: http://www.cdc.gov/hiv/stats/hasrlink.htm. Accessed May 31, 2005.
5. Montgomery JP, Mokotoff ED, Gentry AC, Blair JM. The extent of bisexual behaviour in HIV-infected men and implications for transmission to their female sex partners. AIDS Care. 2003;15(6):829-837.
6. Joint United Nations Programme on HIV/AIDS (UNAIDS) World Health Organization (WHO). AIDS Epidemic Update. Geneva, Switzerland: UNAIDS/WHO; 2004.
7. Comparison of female to male and male to female transmission of HIV in 563 stable couples. European Study Group on Heterosexual Transmission of HIV. BMJ. 1992;304(6830):809-813.
8. Padian NS, Shiboski SC, Glass SO, Vittinghoff E. Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. Am J Epidemiol. 1997;146(4):350-357.
9. Holmes KK, Stamm WE. Lower genital tract infection in females: urethro, cervical, and vaginal infections. In: Holmes KK, Sparling PF, Mardh P-A, et al, eds. Sexually Transmitted Diseases. New York, NY: McGraw-Hill; 1999:761-782.
10. Morrison CS, Bright P, Wong EL, et al. Hormonal contraceptive use, cervical ectopy, and the acquisition of cervical infections. Sex Transm Dis. 2004; 31(9):561-567.
11. Casalini C, Signorini L, Beltrame A, Matteelli A, Carosi G. Vertical transmission of human immunodeficiency virus (HIV) and other sexually transmitted infections (STI) [in Italian]. Minerva Ginecol. 2001;53(3):177-192.
12. Sacks SL, Griffiths PD, Corey L, et al. HSV-2 transmission. Antiviral Res. 2004;63(Suppl 1):S27-S35.
13. Tiller CM. Chlamydia during pregnancy: implications and impact on perinatal and neonatal outcomes. J Obstet Gynecol Neonatal Nurs. 2002; 31(1):93-98.
14. Rottingen JA, Cameron DW, Garnett GP. A systematic review of the epidemiologic interactions between classic sexually transmitted diseases and HIV: how much really is known? Sex Transm Dis. 2001;28(10):579-597.
15. Ferenczy A, Coutlee F, Franco E, Hankins C. Human papillomavirus and HIV coinfection and the risk of neoplasias of the lower genital tract: a review of recent developments. Can Med Assoc J. 2003;169(5):431-434.
16. St Lawrence JS, Montano DE, Kasprzyk D, Phillips WR, Armstrong K, Leichliter JS. STD screening, testing, case reporting, and clinical and partner notification practices: a national survey of US physicians. Am J Public Health. 2002;92(11):1784-1788.
17. United States Preventive Services Task Force. Screening for Infectious Diseases. In: Guide to Clinical Preventive Services. 2nd ed. Baltimore, Md: Lippincott Williams & Wilkins; 1996: 287-345.
18. Sexually transmitted diseases treatment guidelines 2002. Centers for Disease Control and Prevention. MMWR Recomm Rep. 2002;51(RR-6):1-78.
19. McCree DH, Liddon NC, Hogben M, St Lawrence JS. National survey of doctorsÍ actions following the diagnosis of a bacterial STD. Sex Transm Infect. 2003;79(3):254-256.
20. Ness RB, Brunham RC, Shen C, Bass DC, PID Evaluation Clinical Health (PEACH) Study Investigators. Associations among human leukocyte antigen (HLA) class II DQ variants, bacterial sexually transmitted diseases, endometritis, and fertility among women with clinical pelvic inflammatory disease. Sex Transm Dis. 2004;31(5):301-304.
21. Cates W Jr, Wasserheit JN. Genital chlamydial infections: epidemiology and reproductive sequelae. Am J Obstet Gynecol. 1991;164(6 Pt 2):1771-1781.
22. Hillis SD, Joesoef R, Marchbanks PA, Wasserheit JN, Cates W Jr, Westrom L. Delayed care of pelvic inflammatory disease as a risk factor for impaired fertility. Am J Obstet Gynecol. 1993; 168(5):1503-1509.
23. McCormack WM. Pelvic inflammatory disease. N Engl J Med. 1994; 330(2):115-119.
24. Soper DE. Pelvic inflammatory disease. Infect Dis Clin North Am. 1994;8(4): 821-840.
25. Cohen I, Veille JC, Calkins BM. Improved pregnancy outcome following successful treatment of chlamydial infection. JAMA. 1990;263(23):3160-3163.
26. Ryan GM Jr, Abdella TN, McNeeley SG, Baselski VS, Drummond DE. Chlamydia trachomatis infection in pregnancy and effect of treatment on outcome. Am J Obstet Gynecol. 1990; 162(1):34-39.
27. Hollblad-Fadiman K, Goldman SM. American College of Preventive Medicine practice policy statement: screening for Chlamydia trachomatis. Am J Prev Med. 2003;24(3):287-292.
28. Workowski KA, Berman SM. CDC sexually transmitted diseases treatment guidelines. Clin Infect Dis. 2002;35 (Suppl 2):S135-S137.
29. Miller WC, Ford CA, Morris M, et al. Prevalence of chlamydial and gonococcal infections among young adults in the United States. JAMA. 2004; 291(18):2229-2236.
30. Nsuami M, Cammarata CL, Brooks BN, Taylor SN, Martin DH. Chlamydia and gonorrhea co-occurrence in a high school population. Sex Transm Dis. 2004;31(7):424-427.
31. US Department of Health and Human Services. Healthy People 2010. 2nd ed. With Understanding and Improving Health, and Objectives for Improving Health. Vol 1, 2. Washington, DC: US Government Printing Office; 2000.
32. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2003 Supplement, Syphilis Surveillance Report. Atlanta, Ga: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2004.
33. Fox KK, Knapp JS, Holmes KK, et al. Antimicrobial resistance in Neisseria gonorrhoeae in the United States, 1988-1994: the emergence of decreased susceptibility to the fluoroquinolones. J Infect Dis. 1997;175(6): 1396-1403.
34. Wang SA, Lee MV, OÍConnor N, et al. Multidrug-resistant Neisseria gonorrhoeae with decreased susceptibility to cefixime„Hawaii, 2001. Clin Infect Dis. 2003;37(6):849-852.
35. Genc M, Ledger WJ. Syphilis in pregnancy. Sex Transm Infect. 2000; 76(2):73-79.
36. Mellors JW, Munoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med. 1997; 126(12):946-954.
37. Anderson RN, Smith BL. Deaths: leading causes for 2001. Natl Vital Stat Rep. 2003;52(9):1-85.
38. Farzadegan H, Hoover DR, Astemborski J, et al. Sex differences in HIV-1 viral load and progression to AIDS. Lancet. 1998;352(9139):1510-1514.
39. Kalish LA, Collier AC, Flanigan TP, Kumar PN. Plasma human immunodeficiency virus (HIV) type 1 RNA load in men and women with advanced HIV-1 disease. J Infect Dis. 2000; 182(2):603-606.
40. Moore RD, Cheever L, Keruly JC, Chaisson RE. Lack of sex difference in CD4 to HIV-1 RNA viral load ratio. Lancet. 1999;353(9151):463-464.
41. Moroni M. Sex differences in HIV-1 viral load and progression to AIDS. ICONA Study Group. Italian cohort of HIV-1 positive individuals. Lancet. 1999;353(9152):589-590.
42. Sterling TR, Lyles CM, Vlahov D, Astemborski J, Margolick JB, Quinn TC. Sex differences in longitudinal human immunodeficiency virus type 1 RNA levels among seroconverters. J Infect Dis. 1999;180(3):666-672.
43. Napravnik S, Poole C, Thomas JC, Eron JJ Jr. Gender difference in HIV RNA levels: a meta-analysis of published studies. J Acquir Immune Defic Syndr. 2002;31(1):11-19.
44. Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Washington, DC: Department of Health and Human Services; 2005.
45. Benki S, Mostad SB, Richardson BA, Mandaliya K, Kreiss JK, Overbaugh J. Cyclic shedding of HIV-1 RNA in cervical secretions during the menstrual cycle. J Infect Dis. 2004;189(12): 2192-2201.
46. Money DM, Arikan YY, Remple V, et al. Genital tract and plasma human immunodeficiency virus viral load throughout the menstrual cycle in women who are infected with ovulatory human immunodeficiency virus. Am J Obstet Gynecol. 2003;188(1): 122-128.
47. Kontorinis N, Dieterich D. Hepatotoxicity of antiretroviral therapy. AIDS Rev. 2003;5(1):36-43.
48. American Social Health Association. Consumer/Patient Fact Sheet. Research Triangle Park, NC: American Social Health Association, National HPV & Cervical Cancer Prevention Resource Center; 2005.
49. Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002; 55(4):244-265.
50. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338(7):423-428.

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