Infectious Diseases in and Gynecology 7:248-252 (1999) (C) 1999 Wiley-Liss, Inc.

Pelvic Inflammatory Disease in the Postmenopausal Woman

S.L. Jackson* and D.E. Soper Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC

ABSTRACT

Objective: Review available literature on pelvic inflammatory disease in postmenopausal women. Design: MEDLINE literature review from 1966 to 1999. Results: Pelvic inflammatory disease is uncommon in postmenopausal women. It is polymicro- bial, often is concurrent with tuboovarian abscess formation, and is often associated with other diagnoses. Conclusion: Postmenopausal women with pelvic inflammatory disease are best treated with in- patient parenteral antimicrobials and appropriate imaging studies. Failure to respond to should yield a low threshold for surgery, and consideration of alternative diagnoses should be entertained. Infect. Dis. Obstet. Gynecol. 7:248-252, 1999. (C) 1999Wiley-Liss, Inc.

KEY WORDS menopause; tuboovarian abscess; diverticulitis

elvic inflammatory disease (PID) is a common stance abuse, lack of barrier contraception, use of and serious complication of sexually transmit- an intrauterine device (IUD), and vaginal douch- ted diseases in young women but is rarely diag- ing. z The pathophysiology involves the ascending nosed in the postmenopausal woman. The epide- spread of pathogens initially found within the en- miology of PlD,.as well as the changes that occur in docervix, with the most common etiologic agents the genital tract of postmenopausal women, ex- being the sexually transmitted microorganisms plain this discrepancy. The exact incidence of PID Neisseria gonorrhoeae and Chlamydia trachomatis. in postmenopausal women is unknown; however, These bacteria are identified in 60-75% of pre- in one series, fewer than 2% of women with tubo- menopausal women with PID. 3 Other responsible ovarian abscess formation were postmenopausal. microorganisms include respiratory pathogens, Despite the rarity with which PID occurs in the such as Haemophilus influenzae4,s and Streptococcus postmenopausal woman, consideration and early pyogenes, s and -associated micro- recognition of the diagnosis along with appropriate organisms (Prevotella, Peptostreptococcus). 3,6 therapy can decrease the morbidity and mortality Cervical factors play a role in the development associated with what is usually a serious infection. of PID. The columnar epithelium of the endocer- vix is found everted in women of PATHOPHYSIOLOGY commonly repro- ductive age, and this is accentuated with use of oral Pelvic inflammatory disease is an infection of the contraceptive pills. Both N. gonorrhoeae and C. tra- upper genital tract most commonly seen in young chomatis attach preferentially to these columnar en- women. Typically, the risk factors associated with docervical cells. With menopause, the cervical PID are young age, low socioeconomic status, sub- transformation zone is anatomically located within

*Correspondence to: Susan L. Jackson, MD, Department of Obstetrics and Gynecology, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 634, PO Box 250619, Charleston, SC 29425. E-mail: [email protected] Received March 1999 Review Article Accepted 17 June 1999 PELVIC INFLAMMATORY DISEASE IN POSTMENOPA USAL WOMEN JACKSON AND SOPER the endocervical canal and is smaller than in pre- menopausal PID had previous uterine instrumen- menopausal women, decreasing the area of attach- tation, the majority within 2 weeks of the diagno- ment available to C. trachomatis and N. gonorrhoeae. sis. 13 Both a fractionated dilation and curettage ta These changes most likely lower the susceptibility and office sampling with an aspirating pipette can of the postmenopausal woman to infection. The be associated with the development of PID. Ag- endocervix also acts as a functional barrier to as- gressive sampling may lead to uterine perforation, cending infection. This barrier can be attenuated which allows the direct inoculation of microorgan- by the changing rheologic properties of the cervical isms into the peritoneal cavity. mucus as noted during ovulation or breached by Structural abnormalities of the genital tract, such the occurrence of retrograde . Physi- as cervical stenosis, uterine anatomic abnormalities, ologically, the cervical mucus of the menopausal and tubal disease, are also associated with an in- woman is more tenacious and serves as a mechani- creased risk of developing PID.6 A history of cer- cal barrier to ascending infections. Lack of men- vical conization, cryotherapy, or loop electrosurgi- struation in menopausal women decreases the risk cal excision procedure can be associated with the of infection of the upper genital tract. development of cervical stenosis. This, in addition The direct extension of infectious processes to other lesions, such as visible cervical malignan- from adjacent intraabdominal viscera is more likely cies, submucous myomas, and endometrial polyps, to be associated with PID in older women. Disor- can block the efflux of blood or other fluids from ders such as diverticulitis, Crohn disease, colonic the uterine cavity. A collection of fluid within the cancers, and have been associated uterine cavity, such as blood () or with a direct spread of infection to the ovaries, ovi- clear fluid (hydrometra), can become contaminated ducts, and and manifest as a unilateral or with microorganisms, causing a . This in- bilateral tuboovarian abscess. 1,7,8 Fistula formation fected fluid may then reflux into the fallopian from an abscess cavity to the genital tract has also tubes and subsequently into the peritoneal cavity. been described.9,1 A prior history of PID with subsequent tubal scarring or formation results in fallo- RISK FACTORS pian tubes that are more susceptible to nonsexually Older women are less likely to have risk factors transmitted aerobic pathogens, such as H. influen- known to be associated with exposure to sexually zae, group B streptococcus, and . 5 transmitted microorganisms. Behavioral, physi- Chronic or recurring PID, however, appears to be ologic, and anatomic alterations that occur with ad- an uncommon cause of pelvic organ infection in the vancing age offer barriers to the usual means of older population. 14 developing PID. The vaginal flora of postmenopausal women is Sexual activity is a prerequisite for the develop- more likely to be populated with aerobic gram- ment of PID in younger women, and high coital negative bacteria, especially E. coli, particularly if frequency has been associated with acquiring the they do not take replacement therapy. 5 If disease. The precise mechanism determining the these potentially pathogenic bacteria gain entry spread of microorganisms from the lower genital into the upper genital tract and a concomitant ab- tract to the upper genital tract is poorly understood; normality fails to allow the secretions of the upper however, this suggests a role of spermatozoa as a genital tract to be drained, an environment condu- vehicle for transporting the microorganisms to the cive to suppurative infection can occur. Degenera- upper genital tract. Most older women have fewer tion of uterine myomas has been associated with sexual partners and less frequent coital activity, lz bacterial superinfection and infection of the genital making them less likely to develop PID. tract. 6 A risk factor associated with the development of Finally, a "forgotten" IUD may be associated PID in the postmenopausal woman is uterine in- with a more serious genital tract infection. Landers strumentation. Such procedures may introduce mi- et al. revealed that up to one third of women with croorganisms into the endometrial cavity, which tuboovarian abscess currently or were past users of can lead to an infection of the upper genital tract. IUDs. 6 In some cases, infections may be due to One series reported that 45% of women with post- Actinomyces israelii, a gram-positive anaerobic organ-

INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY 249 PELVIC INFLAMMATORY DISEASE IN POSTMENOPA USAL WOMEN JACKSON AND SOPER ism. This infection occurs almost exclusively in Additional laboratory values that may aid in the women who have an IUD in situ. 17 Characteristi- diagnosis include a complete blood count (specifi- cally, these patients have pelvic abscess formation cally to identify a leukocytosis) and C-reactive pro- and may exhibit evidence of fistula development. tein. A Papanicolaou smear of the ecto- and endo- On pelvic exam, palpable indurated masses may be should be obtained if not recently per- present, suggesting a possible genital tract malig- formed. Endometrial biopsy should be considered nancy. and, if obtained, sent for pathologic and microbio- logic evaluation. Computed tomography (CT) or MICROBIOLOGY pelvic ultrasonography should be performed in The postmenopausal woman diagnosed with PID most postmenopausal women with PID, because is less likely to harbor a sexually transmitted organ- the majority will have evidence of a tuboovarian ism than the premenopausal woman. In most re- abscess. 1,7,as-z0 ported cases, 1,7,18,19 the organisms most frequently In premenopausal patients, pelvic organ tender- encountered were E. coli (76%) and Klebsiella ness and either or mucopurulent endo- (43%). These microorganisms were also identified must be present to make the clinical di- in combination in 50-67% of bacteriologic cultures agnosis of PID. Because contiguous spread of in- obtained from the infected tissues. ,7,18 Other bac- fection from diseased adjacent organs is a common teria isolated include Pseudomonas (14%), Staphylo- mechanism of PID in older women, leukorrhea and coccus aureus (<5 %), Staphylococcus albus (<5 %), and mucopurulent endocervicitis may not be present enterococcus spp. ,7,8-z Anaerobic organisms, such on examination in these cases. as Bacteroides fragilis, were recovered in several A review of the literature reveals that the ma- cases. 8,3,19 Other aerobic pathogens, such as H. jority of postmenopausal women with PID have an influenzae and group B streptococcus, may cause an associated tuboovarian abscess. '7'8'1,8,a9 The di- ascending infection, and concomitant genital tract agnosis of this abscess is rarely made preoperatively pathology is likely to be detected. without appropriate imaging studies, and many women develop morbid complications including CLINICAL MANIFESTATIONS colocutaneous fistulas, wound infections, , re- The most common presenting symptoms for post- nal failure, pulmonary embolism, and death. Asso- menopausal women with PID are vaginal spotting ciated findings at surgery include leiomyomas, or bleeding, abdominal pain, fever, nausea, and presence of an IUD, squamous cell carcinoma of change in bowel habits. 1,7,8,13,18 Isolated postmeno- the cervix, adenocarcinoma of the endocervix, en- pausal bleeding is a warning of a potentially serious dometrial polyps, hyperplasia, adenocarcinoma, problem and should prompt an investigation into and epithelial ovarian carcinoma. Extragenital find- its source. Physical examination should begin with ings are primarily bowel related, with diverticulitis, evaluation of vaginal secretions for the presence of appendicitis, inflammatory bowel disease, diver- in the lower genital tract. A wet ticulosis, perforations of the gastrointestinal tract, and mount of vaginal secretions should reveal a pre- colorectal carcinoma among those reported. 1,7,14,18-z dominance of inflammatory cells. Mucopurulent Several series reported that greater than 40% of endocervicitis may be present, with a green or yel- postmenopausal women with PID had an associ- low discharge arising from the endocervix. The cer- ated malignancy. 'a4 vix may also be erythematous and friable (i.e., bleeds easily when touched with a cotton swab). DIFFERENTIAL DIAGNOSES Tests for N. gonorrhoeae and C. trachomatis endo- The most important differential diagnosis to con- cervical infection should be obtained, and a bi- sider in postmenopausal women with PID is acute manual examination should be performed to assess diverticulitis with or without associated pelvic ab- the presence or absence of cervical motion tender- scess. Diverticulitis is the most common nonneo- ness, uterine tenderness, and adnexal tenderness. plastic gastrointestinal disorder associated with the Bimanual examination is likely to reveal the pres- diagnosis of postmenopausal PID. el Women with ence of a pelvic mass, pelvic tenderness, and, oc- diverticulitis will commonly present with a pre- casionally, physical signs of peritoneal irritation. dominance of bowel symptoms, as opposed to the

250 INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY PELVIC INFLAMMATORY DISEASE IN POSTMENOPA USAL WOMEN JACKSON AND SOPER patient with PID. In addition, women with diver- TABLE I. Suggested antimicrobial regimens for the ticulitis do not experience concurrent vaginal treatment of postmenopausal PIDa'b bleeding. Diverticular disease affects 5-10% of the Regimen A Regimen B population over 45 years old, and nearly 80% of Clindamycin, 900 mg Ofloxacin, 400 mg intravenously those over 85; however, only 20% become symp- intravenously every every 12 hours, tomatic. The sigmoid and descending colon are the 8 hours, plus most common sites of involvement. Computed to- plus Clindamycin, 900 mg Gentamicin, intravenous intravenously every 8 hours mography is considered the diagnostic modality of loading dose (2 mg/kg body or choice for the evaluation of suspected diverticulitis weight) followed by a , 500 mg and allows for the exclusion of other intraabdomi- maintenance dose intravenously every 8 hours nal and pelvic pathology, including abscess forma- (I.5 mg/kg) every 8 hours, zz plus tion. Ampicillin, g intravenously Appendicitis is an additional consideration in every 4 hours the differential of the diagnosis postmenopausal aModified from Centers for Disease Control and Prevention. 1998 woman with PID, although it more commonly oc- Guidelines for treatment of sexually transmitted diseases. MMWR curs in the younger population. Diagnostic modali- Morb Mortal Wkly Rep 1998;47(RR-I):79-86. bother options include the extended spectrum penicillins with beta ties useful in the evaluation of appendicitis include lactamase inhibitors (ticarcillin/clavulanate, ampicillin/sulbactam, and pi- ultrasonography and CT. Transabdominal ultra- peracillin/tazobactam), extended spectrum cephalosporins (cefotetan and cefoxitin), and the carbapenems (imipenem/cilastatin and mero- sound examination of the right lower quadrant may penem). reveal a noncompressible tubular structure with thickened muscular walls. Sensitivity and specific- with postmenopausal PID, namely, E. coli and ity of in the diagnosis of appendicitis is Klebsiella spp. In addition, because of the common reported as 76% and 91%, respectively, with a posi- association of tuboovarian abscess formation, anti- tive predictive value of 95%. Computed tomogra- microbial coverage of anaerobic bacteria is manda- phy evaluation of acute appendicitis reveals a posi- tory. Box lists several regimens that are accept- tive predictive value of 96%, with a sensitivity of able for the treatment of postmenopausal PID. 96% and specificity of 89%. Computed tomography These antimicrobial regimens possess a broad has also been shown to be more accurate in the spectrum of activity against aerobic and anaerobic diagnosis of associated periappendiceal abscess, as microorganisms and should penetrate abscess cavi- compared with ultrasound, z3 ties well. has remained the gold standard for Early surgical intervention in the management the diagnosis of PID, because it provides direct of postmenopausal women with PID should be en- visualization of the , as well as other intraab- tertained after excluding the possibility of cervical dominal organs, to confirm the diagnosis and grade carcinoma. These patients commonly have severe the extent of disease. Liberal use of laparoscopy disease characterized by tuboovarian abscess for- should be considered in older women with uncer- mation, and many have complicating medical ill- tain diagnoses following appropriate imaging stud- nesses, such as diabetes and coronary heart disease. ies, because they are more likely to have other in- As a group, they are less resilient than are younger traabdominal pathology associated with the diagno- women with PID and are more likely to manifest sis of PID. severe systemic signs of sepsis, including shock. Mortality rates of 25% have been reported despite TREATMENT adequate antimicrobial and surgical treatment, is Most postmenopausal women with PID will have Moreover, the common association of inflammatory systemic signs of a severe infection and therefore bowel disease, other extragenital pathology, and should be hospitalized. In situ IUDs should be re- genital tract malignancies with PID in this age moved after parenteral antibiotics are instituted. group allows surgical exploration to be both diag- Several antimicrobial regimens can be recom- nostic and therapeutic. Percutaneous drainage of mended for the treatment of PID in this age group. pelvic abscesses has become more common in the Any regimen should possess excellent activity treatment of tuboovarian abscess following failed against the common microorganisms associated antimicrobial therapy; however, this treatment mo-

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