Frank F. Tu

Pelvic Congestion Syndrome-Associated Pelvic Pain: A Systematic Review of Diagnosis and Management

To systematically evaluate the diagnosis and treatment of female pelvic congestion syndrome (PCS). We searched the PubMed database and relevant bibliographies for English-language studies published between January 1966 and May 2009 pertaining to diagnosis and treatment of female PCS-related pelvic pain. Treatment articles were restricted to those containing at least 4 subjects and a specified length of follow-up. Diagnostic test studies were included if they included subjects with and without pelvic pain. Two reviewers abstracted characteristics and outcomes from all controlled diagnostic studies and treatment papers. Six diagnostic and 22 treatment studies met entry criteria. Diagnostic method studies (pelvic venography, magnetic resonance imaging, or ultrasound) generally lacked appropriate reference standards, blinded assessors, or proven reliability. Treatment studies (using transvenous catheter embolization, surgical ligation, hysterectomy, or hormonal suppression) reporting ordinal outcomes found improvement from 24% to 100%; a similarly wide range of improvement was found with change in continuous rating of visual analogue scale pain scores (mean follow-up 4 months to 5.6 years). Both progestins and gonadotropin-releasing hormone agonists are effective in decreasing pain symptoms. The optimal diagnostic approach for PCS-related pelvic pain remains unclear, and controlled trials comparing medical and interventional treatments are urgently needed for PCS-associated pelvic pain. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to Compare different surgical treatments for pelvic congestion syndromes associated with pelvic pain syndromes. Estimate the relative severity of pelvic congestion in women using current venographic criteria. Choose between different diagnostic methods for characterizing pelvic venous blood flow and anatomy in women presenting with pelvic pain.

Increased Pressure Pain Sensitivity in Women With Chronic Pelvic Pain

OBJECTIVE: To determine whether women with chronic pelvic pain and variable degrees of endometriosis demonstrate altered pain sensitivity relative to pain-free healthy women in a control group and whether such differences are related to the presence or severity of endometriosis or comorbid pain syndromes. METHODS: Four patient subgroups (endometriosis with chronic pelvic pain [n=42], endometriosis with dysmenorrhea [n=15], pain-free endometriosis [n=35], and chronic pelvic pain without endometriosis [n=22]) were each compared with 30 healthy women in a control group in this cross-sectional study. All patients completed validated questionnaires regarding pain symptoms and underwent screening for comorbid pain disorders. Pain sensitivity was assessed by applying discrete pressure stimuli to the thumbnail using a previously validated protocol. RESULTS: While adjusting for age and education, pain thresholds were lower in all subgroups of women with pelvic pain relative to healthy women in the control group (all P values <.01). There was no difference in pain thresholds when comparing patients with endometriosis without pelvic pain with healthy women in the control group (mean difference 0.02 kg/m2, 95% confidence interval −0.43 to 0.47). The presence and severity of endometriosis and number of comorbid pain syndromes were not associated with a difference in pain thresholds. CONCLUSION: Women with chronic pelvic pain demonstrate increased pain sensitivity at a nonpelvic site compared with healthy women in a control group, which is independent of the presence or severity of endometriosis or comorbid pain syndromes. These findings support the notion that central pain amplification may play a role in the development of pelvic pain and may explain why some women with pelvic pain do not respond to therapies aimed at eliminating endometriosis lesions. LEVEL OF EVIDENCE: II

The association of dysmenorrhea with noncyclic pelvic pain accounting for psychological factors

OBJECTIVE The factors that underlie pelvic pain are poorly understood. Specifically, the relative influence of dysmenorrhea and psychological factors in the etiology of noncyclic pelvic pain conditions, such as interstitial cystitis and irritable bowel syndrome, is unknown. To further characterize pelvic pain, we compared the frequency of menstrual, somatosensory, and psychological risk factors between women with and without severe noncyclic pelvic pain symptoms. STUDY DESIGN A total of 1012 reproductive-aged women completed a 112-item questionnaire with domains including mood, fatigue, physical activity, somatic complaint, and pain. Questionnaire items included existing items for menstrual distress and newly written items derived from qualitative interviews. The relationship of dysmenorrhea and noncyclic pelvic pain complaints (dyspareunia, dyschezia, or dysuria) was modeled using quantile regression. RESULTS Among women who menstruate regularly, those with dysmenorrhea had disproportionally more severe noncyclic pelvic pain (54/402, 13%) than women without dysmenorrhea (5/432, 1%; odds ratio, 13; 95% confidence interval, 5-33). In a multivariate-adjusted model, dysmenorrhea (β = .17), activity capability (β = .17), somatic complaint (β = .17), and bodily pain (β = .12) were the primary predictors of noncyclic pelvic pain. Depression (β = .03) and anxiety (β = .01) were not significantly predictive. The presence of dysmenorrhea, somatic complaint, and low activity capability predicted 90% of the cases of women with noncyclic pelvic pain. CONCLUSION The association between dysmenorrhea and noncyclic pelvic pain suggests that menstrual pain is an etiological factor in noncyclic pelvic pain, whereas depression and anxiety may be secondary effects. Longitudinal studies are needed to determine whether dysmenorrhea causally influences development of noncyclic pelvic pain or shares common underlying neural mechanisms.

The influence of prior oral contraceptive use on risk of endometriosis is conditional on parity

OBJECTIVE To estimate the influence of prior oral contraceptive pill (OCP) use on future diagnosis of endometriosis in young women. DESIGN Prospective cohort study, the Australian Longitudinal Study on Womens Health. SETTING Community-based sample. PATIENT(S) 9,585 women age 18-23 at study onset. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Risk of self-reported endometriosis estimated with Cox proportional-hazards regression with time-dependent covariates. RESULT(S) Compared with never users, endometriosis hazard ratios in nulliparous women with <5 years and ≥ 5 years of OCP use (preceding diagnosis) were 1.8 (95% CI, 1.30-2.53) and 2.3 (95% CI, 1.59-3.40), respectively. Similar risk was seen in both women reporting infertility and unsure fertility. In parous women with <5 years of use, the hazard ratio for endometriosis was 0.41 (95% CI, 0.15-0.56) and for ≥ 5 years of use was 0.45 (95% CI, 0.16-1.23). Women reporting early noncontraceptive OCP use had a twofold higher risk (odds ratio 2.07; 95% CI, 1.72-2.51). CONCLUSION(S) Prior OCP exposure reduces the risk of diagnosis of endometriosis in parous women but increases it among nulliparous women; these associations appear unaffected by fertility status. An increased risk of endometriosis diagnosis seen in women reporting early noncontraceptive OCP use may explain some of the positive OCP risk seen in nulliparous women.

Gynecologic management of neuropathic pain

Obstetrician/gynecologists often are the initial management clinicians for pelvic neuropathic pain. Although treatment may require comprehensive team management and consultation with other specialists, there are a few critical and basic steps that can be performed during an office visit that offer the opportunity to improve quality of life significantly in this patient population. A key first step is a thorough clinical examination to map the pain site physically and to identify potentially involved nerves. Only limited evidence exists about how best to manage neuropathic pain; generally, a combination of surgical, manipulative, or pharmacologic methods should be considered. Experimental methods to characterize more precisely the nature of the nerve dysfunction exist to diagnose and treat neuropathic pain; however, additional scientific evidence is needed to recommend these options unanimously. In the meantime, an approach that was adopted from guidelines of the International Association for the Study of Pain has been tailored for gynecologic pain.

Multimodal nociceptive mechanisms underlying chronic pelvic pain

OBJECTIVE We sought to evaluate candidate mechanisms underlying the pelvic floor dysfunction in women with chronic pelvic pain (CPP) and/or painful bladder syndrome (PBS)/interstitial cystitis. Notably, prior studies have not consistently controlled for potential confounding by psychological or anatomical factors. STUDY DESIGN As part of a larger study on pelvic floor pain dysfunction and bladder pain sensitivity, we compared a measure of mechanical pain sensitivity, pressure pain thresholds (PPTs), between women with pelvic pain and pain-free controls. We also assessed a novel pain measure using degree and duration of postexam pain aftersensation, and conducted structural and functional assessments of the pelvic floor to account for any potential confounding. Phenotypic specificity of pelvic floor measures was assessed with receiver operator characteristic curves adjusted for prevalence. RESULTS A total of 23 women with CPP, 23 women with PBS, and 42 pain-free controls completed the study. Women with CPP or PBS exhibited enhanced pain sensitivity with lower PPTs (1.18 [interquartile range, 0.87-1.41] kg/cm(2)) than pain-free participants (1.48 [1.11-1.76] kg/cm(2); P < .001) and prolonged pain aftersensation (3.5 [0-9] vs 0 [0-1] minutes; P < .001). Although genital hiatus (P < .01) was wider in women with CPP there were no consistently observed group differences in pelvic floor anatomy, muscle tone, or strength. The combination of PPTs and aftersensation duration correlated with severity of pelvic floor tenderness (R(2), 41-51; P < .01). Even after adjustment for prevalence, the combined metrics discriminated pain-free controls from women with CPP or PBS (area under the curve, 0.87). CONCLUSION Both experimental assessment of pelvic floor pain thresholds and measurement of sustained pain are independently associated with pelvic pain phenotypes. These findings suggest systematic clinical assessment of the time course of provoked pain symptoms, which occurs over seconds for mechanical pain thresholds vs minutes for aftersensation pain, would be helpful in identifying the fundamental mechanisms of pelvic floor pain. Longitudinal studies of therapies differentially targeting these discrete mechanisms are needed to confirm their clinical significance.

The Effects of Platelet-Activating Factor on Uterine Contractility, Perfusion, Hypoxia, and Pain in Mice

It is widely hypothesized that menstrual pain is triggered by prostaglandin synthesis that evokes high-pressure uterine contractions and ischemia. However, the effects of molecules implicated in menstrual pain on uterine contractility, perfusion, and oxygenation in vivo have been rarely demonstrated. Studies in women that do not respond to nonsteroidal anti-inflammatory drugs (NSAIDs) have reported elevated levels of platelet-activating factor (PAF). To establish in vivo evidence of PAF’s capability to impair uterine homeostasis and to elicit visceral pain, we examined the effects of the PAF receptor agonist (carbamyl PAF [CPAF]) in comparison to other molecules hypothesized to play a role in uterine pain in mice. Uterine pressure was increased by oxytocin, prostaglandin F2α (PGF2α), and CPAF. Even in the absence of inflammatory molecules, uterine contractions reduced uterine oxygenation by 38%. CPAF reduced uterine perfusion by 40% ± 8% and elicited further oxygen desaturation approaching hypoxia (9.4 ± 3.4 mm Hg Pao 2). Intraperitoneal injections of CPAF and PGF2α evoked visceral pain and pelvic hyperalgesia in awake wild-type mice. However, pain was not observed in identically injected PAF-receptor knockout mice. Thus, our model provides a demonstration that a molecule implicated in NSAID-resistant dysmenorrhea has a detrimental effect on uterine homeostasis and is capable of causing visceral pain. Our results support the general hypothesis that menstrual cramps are caused by uterine contractions, impaired perfusion, and reduced oxygenation. Since this study was limited to mice, confirmation of these results in humans would be valuable for development of novel therapeutics targeted at inflammatory precursors, contractility, perfusion, and tissue oxygenation.

Dilute versus concentrated vasopressin administration during laparoscopic myomectomy: a randomised controlled trial

To determine if higher‐volume, fixed‐dose administration of vasopressin further reduces blood loss at the time of minimally invasive myomectomy.

Nonsteroidal antiinflammatory drug resistance in dysmenorrhea: epidemiology, causes, and treatment

&NA; Although nonsteroidal antiinflammatory drugs can alleviate menstrual pain, about 18% of women with dysmenorrhea are unresponsive, leaving them and their physicians to pursue less well‐studied strategies. The goal of this review is to provide a background for treating menstrual pain when first‐line options fail. Research on menstrual pain and failure of similar drugs in the antiplatelet category suggested potential mechanisms underlying nonsteroidal antiinflammatory drug resistance. Based on these mechanisms, alternative options may be helpful for refractory cases. This review also identifies key pathways in need of further study to optimize menstrual pain treatment.

Noninvasive experimental bladder pain assessment in painful bladder syndrome

To compare bladder sensitivity between patients with pelvic pain and patients who were pain free, undergoing noninvasive, controlled bladder distension via diuresis. We also sought to measure potential mechanisms underlying bladder sensitivity.