Introduction
Pelvic inflammatory disease (PID) is an acute infection of the female upper genital tract involving the uterus, oviducts, and/or ovaries. The resultant infections include endomet- ritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. More than 750 000 women are diagnosed with acute PID each year [1]. The sequelae of PID include tubal factor infertility, ectopic pregnancy, and chronic pelvic pain.
Pathophysiology
Pelvic inflammatory disease is a polymicrobial infection that was once thought to be exclusively associated with the sexually transmitted organismsNeisseria gonorrhoeaeand Chlamydia trachomatis. However an evolved understanding of the polymicrobial nature of PID has demonstrated that organisms which compromise the endogenous vaginal and cervicalflora, such as those causing bacterial vaginosis, can also lead to ascending pelvic infection and PID. In addition, genital mycoplasms have been isolated in women with PID and are thought to be other organisms that can lead to PID. The Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) randomized trial, the largest treatment trial of mild to moderate acute PID in the USA, found positive N. gonorrhoeaeand/or C. trachomatisin fewer than one-third of patients [2].
The long-term sequelae of PID are caused by the infection-induced inflammation of the fallopian tube and concurrent edema, which leads to a dysfunctional fallopian tube and partial or total tubal obstruction. In addition, the fibrinoid exudate on the serosal surfaces of the pelvic organs causes agglutination of these pelvic organs to each other and Chronic Pelvic Pain, ed. William Ledger, William D. Schlaffand Thierry G. Vancaillie.
Published by Cambridge University Press. © Cambridge University Press 2015. 124
other organs such as bowel and omentum. In the normal healing process, most of this exudate is broken down within 72 hours. However, local response to trauma leads to decreasedfibrinolytic activity and earlyfibrinous adhesions. Permanent vascular adhe- sions are caused by the invasion offibroblasts and blood vessels.
Diagnosis
The clinical presentation of acute PID includes signs and symptoms that are non-specific and highly variable. As such, the definitive diagnosis of acute PID can be difficult.
Unfortunately, delayed treatment of PID can increase the likelihood of long-term seque- lae, including chronic pelvic pain, thus making timely and accurate diagnosis and treat- ment essential. The risk of this morbidity in untreated PID has led to a low threshold for empiric treatment, even among women at low risk or with an unclear diagnosis.
The decision whether to start empiric treatment for PID should take into consideration the patient’s risk factors for development of the disease. Risk factors for the development of PID include presence of lower genital infection withN. gonorrhoeae,C. trachomatis, and/or other organisms that are commonly associated with PID. Other factors associated with an increased risk of sexually transmitted infections, such as young age, lower socioeconomic status, and multiple sexual partners, are also associated with the development of PID. In addition, gynecological procedures that involve instrumentation of the uterus are also associated with an increased risk of pelvic infection. These include endometrial biopsy, dilatation and curettage, surgical pregnancy termination, and hysteroscopy.
Treatment guidelines from the US Centers for Disease Control and Prevention (CDC) recommend empiric treatment of women at risk for sexually transmitted diseases, includ- ing sexually active young women who present with lower abdominal/pelvic pain and cervical motion tenderness, uterine tenderness, or adnexal tenderness. Signs of lower genital tract inflammation, including vaginal leukocytosis on wet mount, cervical exudate, or cervical friability can increase the specificity of the diagnosis. The absence of leukocytes on a wet mount makes the diagnosis of PID very unlikely. Other clinical criteria that can increase the specificity of the diagnosis include temperature >37.8°C (101°F), elevated erythrocyte sedimentation rate, elevated C-reactive protein, and documented cervical infection withN. gonorrhoeaeorC. trachomatis. Of course, it is important to recognize that not all cases of PID result from sexually transmitted infection, and a negative test for gonorrhea or chlamydia does not exclude the possibility of PID.
A more definitive diagnosis can be achieved with endometrial biopsy, laparoscopy, and/or pelvic imaging showingfindings consistent with pelvic infection. While these criteria are the most specific, they are not usually necessary to start treatment. Because of their increased invasiveness and cost, these diagnostic modalities are usually reserved for situations where further diagnostic certainty is needed.
Management
Oral and parenteral treatments have been shown to have similar clinical efficacy for women with mild or moderate PID [1]. In addition, data have shown that long-term outcomes, including chronic pelvic pain, are similar among groups of women treated as inpatients and outpatients [2]. As such, most patients can be treated as outpatients. The CDC recommends at least 24 hours of direct inpatient observation for women with tubo- ovarian abscesses. In addition, significant improvement should be seen after 72 hours of
antibiotic treatment for PID. If this is not the case, hospitalization is recommended. Other reasons for inpatient treatment of PID include pregnancy, inability to tolerate oral treat- ment because of nausea/vomiting, and severe clinical illness.
Boxes 11.1and11.2outline the current CDC guidelines for treatment of PID in the inpatient and outpatient setting.
Chronic pelvic pain after pelvic in fl ammatory disease
Despite excellent cure rates for infectious etiologies of PID, rates of chronic pelvic pain after PID have been found to be high. Clinical signs of PID cure do not correlate with a decreased risk of development of chronic pelvic pain and other PID-related sequelae [3]. A subanalysis of PEACH trial data including over 700 women found that 36% of these women experienced chronic pelvic pain over a mean follow-up time of 35 months [4]. A separate subanalysis of PEACH data found a strong association between recurrent PID and the development of chronic pelvic pain [5].
Acute pain caused by PID is thought to result from an inflammatory response to the infectious process that activates the nociceptors of the pelvic viscera. These nociceptors are very responsive to stimuli such as distention, traction, ischemia, and inflammation.
After repetitive stimulation of nociceptors, there is an augmentation of central pain processing that is independent of peripheral stimulation of nociceptors. Many potential mechanisms are thought to contribute to augmented central pain processing. The two mechanisms most described in the literature are loss of descending analgesia and central sensitization. Both of these mechanisms are thought to modulate the pain response in the dorsal horn of the spinal cord.
Box 11.1 Centers for Disease Control and Prevention recommendations for parenteral treatment of pelvic inflammatory disease
Regimen A
Cefotetan 2 g IV every 12 hours or
Cefoxitin 2 g IV every 6 hours plus
Doxycycline 100 mg orally every 12 hours
Regimen B
Clindamycin 900 mg IV every 8 hours plus
Gentamicin: loading dose IV or IM (2 mg/kg body weight), followed by maintenance dose (1.5 mg/kg) every 8 hours
or
Gentamicin single daily dose (3–5 mg/kg) Alternative
Amplicillin/sulbactam 3 g IV every 6 hours plus
Doxycycline 100 mg orally or IV every 12 hours IM, intramuscular; IV, intravenous.
This process of central pain amplification could explain why some women suffer from chronic pelvic pain long after the acute insult of PID, even in the absence of ongoing peripheral nociceptive input. The pain associated with PID can be chronic and widespread and, similar to other chronic pain syndromes, may be characterized by allodynia and reduced pain thresholds. Such pain can be out of proportion to the anatomical abnormalities that may be seen at the time of laparoscopy in these patients. This central- ized pain does not always respond to multiple courses of antibiotics or surgical therapy, and use of medications that modulate the pain regulatory system (e.g. gabapentin, amitriptyline) should be considered.
Pelvic adhesive disease and chronic pelvic pain
Pelvic adhesions can result from tissue inflammation and trauma caused by the PID infectious process. This process begins quickly withfibrinous exudate forming within three hours after tissue injury. While the association between PID and pelvic adhesive disease may be well established, the association between pelvic adhesive disease and chronic pelvic pain is somewhat less clear for several reasons.
First, despite efforts to use imaging techniques to evaluate pelvic adhesive disease, surgical evaluation remains the only definitive way to diagnose these adhesions.
Unfortunately, surgery itself is known to be a significant contributor to adhesive disease.
Adhesions are identified in the majority of women who have undergone a previous Box 11.2 Centers for Disease Control and Prevention recommendations for oral treatment of pelvic inflammatory disease
Regimen A
Ceftriaxone 250 mg IM in a single dose plus
Doxycycline 100 mg orally twice a day for 14 days with or without
Metronidazole 500 mg orally twice a day for 14 days
Or Regimen B
Cefoxitin 2 g IM in a single doseand probenecid 1 g orally administered concurrently as a single dose
plus
Doxycycline 100 mg orally twice a day for 14 days with or without
Metronidazole 500 mg orally twice a day for 14 days
Or Regimen C
Other parenteral third-generation cephalosporin (e.g. ceftizoxime or cefotaxime) plus
Doxycycline 100 mg orally twice a day for 14 days with or without
Metronidazole 500 mg orally twice a day for 14 days IM, intramuscular.
gynecological surgery, with over 80% of women having adhesions at the time of a second- look procedure [6]. These rates are highest in women who have undergone previous laparotomy, but the rate of adhesive disease after laparoscopic procedures is still high. In addition, most women who undergo surgical adhesiolysis develop recurrent postoper- ative adhesions, with some women developing worse pelvic adhesive disease. There is also difficulty in attributing chronic pelvic pain to pelvic adhesive disease because so many other etiologies, both identifiable at the time of surgery and not, can cause chronic pelvic pain. Ultimately, not all patients with pelvic adhesive disease suffer from chronic pelvic pain, making the pathophysiological causality of chronic pelvic pain arising from adhesions difficult to explain. Nervefibers have been identified in pelvic adhesions, but the presence or absence of these nerve fibers does not correlate with the presence or absence of reported pelvic pain.
There are data to suggest that surgical adhesiolysis improves pelvic pain in the short term;
however long-term pain benefits have not been clearly established. The exception may be women with severe pelvic adhesions who may benefit from surgical adhesiolysis. A random- ized trial comparing laparoscopic lysis of adhesions and diagnostic laparoscopy found no difference in quality of life and abdominal pain scores 12 months following surgery [7].
Prevention of pelvic adhesive disease is an area of particular interest in light of the potential benefits it may provide. Minimally invasive surgical techniques and proper tissue handling at the time of surgery may help to reduce postoperative adhesions, although studies have shown the development of adhesive disease despite these tech- niques. Anti-inflammatory agents such as dexamethasone and promethazine, and periton- eal instillates including crystalloid solutions and heparin, have not consistently been found to reduce the risk of postoperative adhesion formation. While certain surgical adhesions barriers such as Seprafilm, Interceed, and the Gore-Tex Surgical Membrane have been shown in some studies to reduce postoperative adhesions, there is no good evidence that their use decreases the likelihood of chronic pelvic pain [8].
Conclusions
Many studies have shown a relationship between PID and chronic pelvic pain. Practitioners should be vigilant about appropriately diagnosing and treating acute PID in order to decrease the risk of long-term sequelae such as chronic pelvic pain. Unfortunately, treat- ment for acute PID does not guarantee that a patient will not have chronic pelvic pain in the future. Ultimately, evaluation and treatment of this pelvic pain should consider all possible causes. In terms of adhesive disease, there are currently insufficient data to support adhesiolysis as a viable, definitive solution for pelvic pain. Consequently, other treatment modalities should be utilized before an attempt at surgical treatment.
References
1. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2010.MMWR 2010;59(RR-12):63–7.
2. Ness RB, Soper DE, Holley RL,et al.
Effectiveness of inpatient and outpatient treatment strategies for women with pelvic
inflammatory disease: results from the Pelvic Inflammatory Disease
Evaluation and Clinical Health (PEACH) Randomized Trial.Am J Obstet Gynecol 2002;186:929–37.
3. Trautmann GM, Kip KE, Richter HE,et al.
Do short-term markers of treatment
efficacy predict long-term sequelae of PID?
Am J Obstet Gynecol2008;198:30.
4. Haggerty CL, Peipert JF, Weitzen S, et al. Predictors of chronic pelvic pain in an urban population of women with symptoms and signs of pelvic
inflammatory disease.Sex Transmit Dis 2005;32:293–9.
5. Trent M, Bass D, Ness RB,et al.
Recurrent PID, subsequent STI, and reproductive health outcomes:findings from the PID evaluation and clinical health (PEACH) study.Sex Transmit Dis 2011;38:878–81.
6. Diamond MP, Singh M, Puscheck EE.
Chronic pelvic pain and adhesions.
In Vercellini P, ed.Chronic Pelvic Pain. Oxford: Wiley-Blackwell, 2011, pp. 71–6.
7. Swank DJ, Swank-Bordewijk SCG, Jop WCJ,et al. Laparoscopic adhesiolysis in patients with chronic abdominal pain: a blinded randomized controlled multi-centre trial.Lancet 2003;361:1247–51.
8. Practice Committee of the American Society for Reproductive Medicine.
Pathogenesis, consequences, and control of peritoneal adhesions in gynecologic surgery: a
committee opinion.Fertil Steril 2013;99:1550–5.
12 dysfunction: cause and e ff ect
12
William D. Petok
Introduction
Healthy sexual function is a source of intimacy, satisfaction, and pleasure for most individuals. Contrary to the Marquis de Sade’s assertion that “sex without pain is like food without taste,”most who suffer from chronic pelvic pain (CPP) would gladly opt for a blander experience. As Vancaillie points out inChapter 1,“the impact of pelvic pain on sexual function should not surprise anyone.”
When interruptions to normal sexual function occur, people can experience frustra- tion, loss, depression, and a host of other reactions. Because of its protracted nature, CPP can produce a variety of sexual problems, not always pain related. In addition to dyspar- eunia and vaginismus, a reduced desire for sex is often a concomitant diagnosis. Formerly known as Hypoactive Sexual Desire Disorder, the new nomenclature of theDiagnostic and Statistical Manual, 5th edition (DSM-V) [1] labels this as Female Sexual Interest/Arousal Disorder. The DSM-V includes the new Genito-Pelvic Pain/Penetration Disorder, which combines dyspareunia and vaginismus from the previous editions.
History Dyspareunia
Painful intercourse has been reported for over 3000 years [2]. Often ascribed to menstrual irregularity, it was later attached to vulvar conditions that caused pain during intercourse by Soranus of Ephesus. Anatomical mismatches from extraordinarily long penises were seen as a cause by Hildanus, a physician of the sixteenth century in Europe. In 1874, the Chronic Pelvic Pain, ed. William Ledger, William D. Schlaffand Thierry G. Vancaillie.
Published by Cambridge University Press. © Cambridge University Press 2015. 130
modern term dyspareunia, from the Greek for“difficult or painful mating”was estab- lished by Barnes. He focused on the primary clinical complaint in his patients: difficult intercourse because of pain [2].
Unfortunately, focus on the sexual component rather than the pain itself produced a classification as a sexual problem rather than a pain problem. Binik suggested that in the early twentieth century the psychoanalytic movement shifted thinking away from physical pathology and toward“hysterical”symptoms and, therefore, into the realm of psychosexual dysfunction. Prior to DSM-V, a variety of medical problems that cause pain (e.g. vulvodynia, vulvar vesitibulitis syndrome (VVS), vestibulodynia, dysesthetic vulvo- dynia) had all been grouped together over time under the dyspareunia label in DSMs.
These individual disorders certainly produce pain in patients that can lead to difficult intercourse. However, they are pain problems and not sexual problems. They can lead to sexual problems but have been incorrectly categorized as such. Binik [2] highlighted that other pain problems are not categorized by the function with which they interfere.
Consequently, it is unusual that pain that interrupts sexual function would be classified as a sexual problem in the DSM.
Vaginismus
Until DSM-V, vaginismus was characterized by vaginal spasm as the crucial diagnostic criterion for the disorder. Trotula of Salerno was probably thefirst to describe a“tighten- ing of the vulva so that even a woman who has been seduced may appear a virgin”[3].
Sims coined the term vaginismus, describing an“involuntary spasmodic closure of the mouth of the vagina, attended with such excessive supersensitiveness as to form a complete barrier to coition.”Masters and Johnson similarly described pelvic musculature spasms that were an involuntary reflex that severely limited if not prevented a woman’s ability to engage in intercourse. Earlier editions of the DSM utilized this scheme and placed vaginismus in its own category and distinctly different from dyspareunia.
Many clinicians are familiar with Masters and Johnson’s description of a woman with vaginismus during a pelvic examination [4, pp. 250–251]:
The literature has remarked on an unusual physical response pattern of a woman afflicted with vaginismus. She reacts in an established pattern to psychological stress during a routine pelvic examination that includes observation of the external genitalia and manual vaginal exploration. The patient usually attempts to escape the examiner’s approach by withdrawing toward the head of the table, even raising her legs from the stirrups, and/or constricting her thighs in the midline to avoid the implied threat of the impending vaginal examination.
Frequently this reaction pattern can be elicited by the woman’s mere anticipation of the examiner’s physical approach to pelvic examination rather than the actual act of manual pelvic investigation.
As Binik [3] has noted, there are no published instruments that translate self-report into a diagnosis of vaginismus. Nothing exists to confirm the presence of the required spasm.
Masters and Johnson believed that an accurate diagnosis of vaginismus could not be made without a pelvic examination. This would leave all mental health professionals, save those rare psychiatrists who perform such diagnostic tests, incapable of making the diagnosis.
Gynecological investigation or self-report would then be necessary for proper diagnosis.
But by 2000 no one had empirically demonstrated that muscle spasms characterized
vaginismus, that it could be differentiated from dyspareunia, or that it could be reliably diagnosed. No suggestion was made in the DSM that women be asked if they experienced spasm even though that would be a normal investigative question for spasms in other parts of the body. A review of the literature on diagnosis of vaginismus yields the striking observation that after 150 years “there is no empirical evidence to support vaginal/
pelvic muscle spasms as the defining characteristic of vaginismus. While it appears possible that a subset of women currently diagnosed with vaginismus do suffer from vaginal/pelvic spasm, it is likely a minority” [3, p. 282]. Furthermore, the defining characteristic of the majority of women diagnosed with vaginismus is vulvar pain. The conclusion is“there is converging empirical consensus on two issues: (1) Muscle spasm is not an adequate defining characteristic for vaginismus; (2) As currently defined by the DSM-IV-TR, vaginismus and “penetration type”or “superficial” dyspareunia resulting from VVS cannot be reliably differentiated”[3, p. 284].
With the publication of DSM-V, the entities of dyspareunia and vaginismus were combined to the more accurately descriptive Genito-Pelvic Pain/Penetration Disorder.
Diagnosis requires“persistent or recurrent difficulties with one (or more) of the following:
1. Vaginal penetration during intercourse. 2. Marked vulvovaginal or pelvic pain during vaginal intercourse or penetration attempts. 3. Marked fear or anxiety about vulvovaginal or pelvic pain in anticipation of, during, or as a result of vaginal penetration. 4. Marked tensing or tightening of the pelvicfloor muscles during attempted vaginal penetration.” A minimum duration of six months and clinically significant distress are necessary conditions from the above symptoms. Of note, the dysfunction is not“better explained by a non-sexual mental disorder or as a consequence of severe relationship distress (e.g. partner violence) or other significant stressors. . ..” This last requirement attends to the multifactorial nature of most sexual problems and highlights relationship issues that were not previously addressed in earlier diagnostic manuals yet are clearly important in understanding a patient’s presenting problem.
Causes
Previous chapters have discussed the range of disorders that can cause pelvic pain. All of these can impact sexual function with different profiles. The pathophysiology is well discussed inChapter 1. The following discussion will highlight the sexual nature of reports that patients will provide for the various diagnostic entities.
Vulvar vesitibulitis syndrome tends to produce pain on vestibular touch or attempted vaginal entry. Women with this disorder report a severe burning type of pain at the entrance to the vagina with contact of sexual and non-sexual nature. These women also can have increased pelvicfloor muscle tension, which is possibly a protective reaction or a condi- tioned response to vulvar pain, much in the same way that pain can be associated with diminished sexual interest (seeChapter 8). Patients with VVS report lower levels of sexual desire, arousal, pleasure, orgasmic success, and lower frequencies of intercourse [5]. They also can have elevated anxiety, depression, hypervigilance to pain stimuli, catastrophization regarding pain, shyness, and lowered sexual self-esteem. It is unclear if these are pre-existing conditions or the result of their pain problems. Finally, while studies of sexual abuse indicate that psychological stressors are more common in patients with persistent pain, they are inconclusive as to whether or not abuse plays a role in women with VVS or any other chronic pain condition.