Prevalence of gynecological disorders in women with symptomatic pelvic venous disorders

Conception and design: SS, GL, TS, RK, SL, PP Analysis and interpretation: SS, NM, PP Data collection: SS, GL, RK, PP Writing the article: SS, TS, PP Critical revision of the article: SS, NM, GL, TS, RK, SL, PP Final approval of the article: SS, NM, GL, TS, RK, SL, PP Statistical analysis: SS, NM, PP Obtained funding: RK, SL, PP Overall responsibility: PP

This study was funded by a grant from the Lakhanpal Vein Foundation .

We conducted a retrospective cohort analysis of prospectively collected data from January 2017 to March 2024, from our Office of the National Coordinator for Health Information Technology certified electronic medical record (Nextgen Healthcare Information Systems) at the Center for Vascular Medicine (CVM). Institutional review board approval for the investigation was obtained (Advarra). Informed consent was not required as per the institutional review board. Women with symptomatic PVI secondary to iliac vein outflow disease with or without ovarian vein reflux were included in the study. Patients with asymptomatic iliac vein stenoses, no evidence of a PeVD, and patients who did not undergo an intervention were excluded from the investigation. It is our protocol at CVM that all patients receive a thorough evaluation by a gynecologist for nonvenous-related causes of CPP before considering interventions for symptomatic PVI. Once other pelvic pain causes are ruled out, a CVM venous specialist evaluates patients for the presence of symptomatic PVI. A venous specialist is defined as a physician who dedicates their practice to the care of patients with venous disease. At CVM, this consists of board-certified physicians in either vascular surgery, cardiology, gynecology or cardiothoracic surgery. We also use advanced practice nurses and physician assistants to optimize the intake process. All patients with a negative gynecological assessment for CPP, a history of pelvic pain, dyspareunia, postcoital pain, urinary frequency, flank pain, abdominal bloating and/or clinical evidence of lower extremity pelvic escape veins, and leg pain/swelling with a negative infrainguinal duplex scan were evaluated with transabdominal ultrasound as per our previously published protocol. Patients with clinical symptoms and positive transabdominal ultrasound findings were offered, diagnostic venography, intravascular ultrasound examination, and possible iliac vein stenting. Patients were separated into three evaluation groups: Patients with pelvic pain alone, patients with PVI and leg symptoms alone, and patients with combined leg and pelvic symptoms. Patient demographics, prevalence of concomitant gynecological disorders, presenting symptoms, Clinical, Etiology, Anatomy, Pathophysiology (CEAP) class, rVCSS, pre and post visual analog pain scores (VAS), stent type, and vein territory covered were assessed. All treated women underwent a diagnostic venogram, which consisted of an anterior-posterior view of the bilateral iliac veins, inferior vena cava, left renal vein, left ovarian veins, and any pelvic veins. Balloon occlusion venography of the internal iliac veins and interrogation of the right ovarian vein was not performed routinely. All patients had a pre and post stenting, intravascular ultrasound examination for the identification of an area reducing lesion of the iliac veins and confirmation of good wall apposition and appropriate stent expansion. If a residual stenosis required postdeployment venoplasty, a completion intravascular ultrasound examination was performed to ensure proper expansion of the residual stenosis. Antiplatelet therapy after stent implantation is not used. Anticoagulation with a factor Xa inhibitor for 90 days after stent implantation is used at the discretion of the treating physician. Indications for extending anticoagulation past 90 days is the presence of thrombus layering as identified on duplex scanning, a residual stenosis, or the presence of intraluminal post-thrombotic scar tissue. Discriminative data were calculated using χ 2 analysis and continuous categorical values were analyzed using analysis of variance. The statistical software program GraphPad Prism, version 10.0 was used to perform all calculations.

From January 2017 to March 2024, 2544 women with a PeVD secondary to PVI were treated at the CVM. Of these patients, 70 presented with pelvic pain alone, 1012 with leg pain alone, and 1454 with mixed symptoms. Table I outlines the demographics of the study cohort. The average age of the treated patients was 52.0 ± 13.8. Racial distribution was 49% White, 16% African American, 11% Hispanic, 1% Asian, and 23% unknown. The most common gynecological disorders reported were uterine fibroids (4%), endometriosis (4.4%), ovarian cysts (2.8%), and polycystic ovarian syndrome (1.5%). Average follow-up was 2.32 ± 2.4 years. Fig 1 , A and B , demonstrate the CEAP class by limb of each treatment group. The majority of patients in all groups were either CEAP class 2, 3, or 4a. Preintervention and postintervention VAS scores by study group and symptom type were ( Table II ): pelvic (7.61 ± 3.72/1.93 ± 3.2), leg (6.18 ± 2.95/2.42 ± 3.2), and mixed (5.72 ± 3.72/2.4 ± 3.1) ( P ≤ .05). For women with a history of endometriosis, pre and post VAS scores were 6.52 ± 3.15 and 2.5 ± 0.6 ( P ≤ .05). There was no difference in pre and post VAS scores in women with a history of endometriosis compared with the other presenting symptom groups. A total of 1738 stents were placed: 27 pelvic, 564 leg, and 935 mixed. The most common stent diameters and lengths were 14 and 16 mm and 120, 140, and 160 mm, respectively ( Fig 2 ). The left common and external iliac veins were the most common vein territories covered ( Fig 3 ). There were 768 reinterventions for a 25.6% reintervention rate at 25 ± 24 months. Table I Patient demographics by presentation type Total (n = 2544) Pelvic pain (n = 70) Leg pain (n = 1012) Mixed (pelvic + leg, (n = 1454) P value Age, years 52 ± 13.8 38.6 ± 13.8 56.8 ± 13.8 47.9 ± 13.8 .001 BMI, kg/m 2 31.29 25.3 ± 7.5 31.6 ± 7.5 30.7 ± 7.5 .01 Sex  Male 0 0 0 0  Female 2554 70 1012 1454 Race  American Indian/Alaskan 5 (0.20%) 0 (0.00%) 2 (0.20%) 3 (0.21%) .93  Asian 26 (1.02%) 0 (0.00%) 8 (0.79%) 18 (1.24%) .38  Black/African 406 (15.96%) 5 (7.14%) 193 (19.07%) 207 (14.24%) .007  Hispanic/Latino 286 (11.24%) 4 (5.71%) 81 (8.00%) 200 (13.76%) .99  Indian 7 (0.28%) 0 (0.00%) 3 (0.03%) 4 (0.28%) .9  White 1237 (48.62%) 18 (25.71%) 508 (50.20%) 706 (48.56%) .0004  Native Hawaiian or Pacific Islander 1 (0.04%) 0 (0.00%) 0 (0.00%) 1 (0.07%) .69  Other race 9 (0.35%) 0 (0.00%) 3 (0.30%) 6 (0.41%) .78  Multiracial 4 (0.16%) 0 (0.00%) 2 (0.20%) 2 (0.14%) .89  Unknown/not reported 457 (17.96%) 42 (60%) 168 (16.60%) 246 (16.92%) .99  Declined 106 (4.17%) 1 (1.43%) 43 (4.25%) 61 (4.20%) .51 Medical history  DM 389 (15.29%) 2 (2.86%) 205 (20.26%) 181 (12.45%) .53  HTN 1257 (49.41%) 7 (10%) 628 (62.06%) 620 (42.64%) .96  CAD 58 (2.28%) 0 (0.00%) 30 (2.96%) 28 (1.93%) .10  HLD 738 (29.01%) 5 (7.14%) 362 (35.77%) 369 (25.38%) .75 Gynecological history  Fibroids 96 (3.77%) 0 (0.00%) 41 (4.05%) 55 (3.78%) .23  Endometriosis 113 (4.44%) 5 (7.14%) 17 (1.68%) 90 (6.19%) .76  Ovarian cysts 53 (2.08%) 2 (2.86%) 14 (1.38%) 37 (2.54%) .08  PCOS 39 (1.53%) 1 (1.43%) 3 (0.30%) 35 (2.41%) .20  PID 1 (0.04%) 0 (0.00%) 1 (0.10%) 0 (0.00%) .47  Hysterectomy 787 (31%) 9 452 326 .001 BMI, Body mass index; CAD, coronary artery disease; DM, diabetes mellitus; HLD, hyperlipidemia; HTN, hypertension; PCOS, polycystic ovarian syndrome; PID, pelvic inflammatory disease. Values are mean ± standard deviation or number (%). Fig 1 (A) Clinical, Etiology, Anatomy, Pathophysiology ( CEAP ) class by category for the right limb. (B) CEAP class by category for the left limb. Table II Visual analog pain scores ( VAS ) and revised Venous Clinical Severity Scores ( rVCSS ) by presentation type VAS scores Presenting pelvic pain (n = 70) Presenting leg pain (n = 1012) Presenting mixed pelvic and leg pain (n = 1454) No. of patients with each presenting pelvic symptom Gynecological symptoms  Pelvic pain at rest 7.61 ± 3.72 0 5.72 ± 3.72 1248  Dysmenorrhea 4.97 ± 3.90 0 4.19 ± 3.90 756  Dyspareunia 5.61 ± 3.62 0 4.17 ± 3.62 596  Vaginal or perineal pain 4.75 ± 2.41 0 1.59 ± 2.41 92 Leg symptoms  Maximum lower extremity 0 6.18 ± 2.9 6.49 ± 2.9  Right leg pain 0 4.61 ± 3.3 5.19 ± 3.3  Left leg pain 0 5.32 ± 3.2 6.49 ± 3.2 rVCSS right 0 5.5 ± 2.9 5.3 ± 2.9 rVCSS left 0 5.5 ± 2.9 5.4 ± 2.9 Values are mean ± standard deviation unless otherwise indicated. Fig 2 Stent types, diameters, and lengths used. Fig 3 Iliac vein territories where stents were placed. IVC, inferior vena cava; LCFV , left common femoral vein; LCIV , left common iliac vein; LEIV , left external iliac vein; LVIC , left common iliac vein; RCIV , right common iliac vein; REIV , right external iliac vein. Patient demographics by presentation type BMI, Body mass index; CAD, coronary artery disease; DM, diabetes mellitus; HLD, hyperlipidemia; HTN, hypertension; PCOS, polycystic ovarian syndrome; PID, pelvic inflammatory disease. Values are mean ± standard deviation or number (%). (A) Clinical, Etiology, Anatomy, Pathophysiology ( CEAP ) class by category for the right limb. (B) CEAP class by category for the left limb. Visual analog pain scores ( VAS ) and revised Venous Clinical Severity Scores ( rVCSS ) by presentation type Values are mean ± standard deviation unless otherwise indicated. Stent types, diameters, and lengths used. Iliac vein territories where stents were placed. IVC, inferior vena cava; LCFV , left common femoral vein; LCIV , left common iliac vein; LEIV , left external iliac vein; LVIC , left common iliac vein; RCIV , right common iliac vein; REIV , right external iliac vein.

The differential diagnosis of the etiology of CPP in women is extensive and includes gynecological pathologies, urological, musculoskeletal, pelvic floor dysfunction, psychological diagnoses, and PVI. 1 , 2 , 3 , 4 , 5 , 7 , 12 , 13 Owing to the variety of possible pathologies related to CPP, it is currently recommended that women undergo a thorough gynecological evaluation before referral to other specialists. PVI is increasingly recognized as a common cause for CPP and has been reported to be a primary etiology in ≤30% of CPP patients. 8 It is currently unknown if PVI is associated with the presence of other causes of pelvic pain and specifically if PVI and gynecological causes occur together or independent of each other. A prospective observational investigation performed in an outpatient gynecological clinic in the United Kingdom performed transvaginal ultrasound assessment on 1500 patients. 14 Uterine vein diameters and types of pelvic pathologies were analyzed. Of the examined patients, 1014 (67%) were reported to have gynecological pathologies. The remaining 486 normal investigations served as the control group for uterine vein diameter measurements. Multivariate analysis indicated that uterine vein diameter dilatation was associated with premenopausal status, high parity, Black ethnicity, and the presence of fibroids >50 mm. Single and multiple type pathologies were observed in 67.1% and 32.9% of patients. respectively. The pathologies identified were adenomyosis (13.7%), fibroids (23.2%), ovarian/adnexal cysts (12.3%), polycystic ovarian morphology (12.8%), endometriosis (2.4%), other (2.6%), and a combination of these in 32.9%. There was no mention of the incidence of PVI in this investigation. To try and determine the incidence of PVI in women with pelvic pain and the response to medical management of the pain with a gonadotrophin-releasing hormone agonist (Goserelin acetate) or medroxyprogesterone acetate, a prospective trial was conducted by Soysal et al. 15 Women with CPP were evaluated with a pelvic examination, venography, laparoscopy, ultrasound assessment, and a questionnaire to assess psychological status and sexual functioning. Of 148 enrolled patients, organic pelvic pathology was identified in 93 (63%) patients, 11 (7%) of whom had concomitant PVI. The most common organic pathologies identified were endometriosis (n = 58, 39%), pelvic inflammatory disease (n = 17 [11%]), postoperative adhesions (n = 15 [10%]), and uterine disease (myoma, n = 4 [2.7%] and adenomyosis, n = 1 [1%]). In the 11 patients with PVI and organic pathology, 5 had endometriosis, 4 pelvic inflammatory disease, 1 myoma, and 1 adenomyosis. In 47 patients (31%), PVI was the only detected abnormality. In the remaining eight patients (5.4%), referral for a psychiatric evaluation was recommended. In the asymptomatic control group, there was no venographic evidence of PVI. The authors concluded that “pelvic congestion syndrome is a distinct clinical entity.” We would further add that, based on the observations of the current investigation, PVI more often than not, presents as the sole cause of CPP and is usually not associated with concomitant organic pelvic pathology. The most common gynecological disorder reported in our PVI population was endometriosis (4.4%). The are >6 million women in the United States with a history endometriosis and ≤71% of these patients complain of CPP, dysmenorrhea, and/or dysparunia. 9 Endometriosis is defined histologically and clinically. Histologically, biopsies demonstrate extrauterine lesions consisting of endometrial glands, endometrial stroma, and/or hemosiderin-laden macrophages. Based on location and depth, lesions are further delineated as superficial, peritoneal, or deep. 9 Clinically, endometriosis can be described as a cycle-dependent, chronic, inflammatory, systemic disease that commonly presents as pelvic pain. This definition is important because CPP secondary to PVI is usually not cyclical and pain is characterized as dull, primarily localized to one side, more likely to shift to both sides, and more likely associated with sharp flares. Pain is generally not present in the morning, is exacerbated by standing and walking, worse at the end of the day, improves with lying down, and is associated with dyspareunia and postcoital ache that can last ≤1 to 2 days. 8 A sensitivity of >70% for diagnosing PVI are symptoms of postcoital ache, deep dyspareunia, increased pain with prolonged standing, and signs of vulvar varicosities and ovarian point tenderness. 8 , 9 Based on these differences, a good history, physical examination, and ultrasound examination should be able to differentiate endometrial pain from PVI pain in the majority of cases. Soysal et al 15 observed that 7% of their patients with PVI had a concomitant gynecological cause of their pelvic pain. Our investigation indicates that, in patients with concomitant disease, the treatment of PVI significantly decrease pelvic pain, despite the history of endometriosis. Therefore, the simultaneous existence of both entities should not be a contraindication to treating a patient with symptomatic PVI. Some reports suggest that organic pelvic pathology may cause ovarian vein dilatation. 14 As stated previously, Amin et al 14 reported uterine and ovarian vein dilatation in women with fibroids >50 mm, but not in women with endometriosis. However, Pacheco et al 16 reported that, in 25 women with endometriosis, 80% demonstrated ovarian vein varices in the broad ligament with a transvaginal ultrasound assessment. In 23 women without endometriosis, 26.1% demonstrated broad ligament ovarian varices. The authors speculate that angiogenic activities associated with endometrial implants and hormonal variation may stimulate ovarian vein dilatation in these patients. Given the small sample size of this report, the generalizability of this observation should be questioned. It seems more plausible that patients with CPP have a high incidence of PVI and that a small percentage of patients with concomitant organic disease exist, as suggested by Soysal et al. 15 The major limitation of this investigation is the retrospective analysis of prospectively collected data. It is unknown whether patients with gynecological organic disease demonstrated active disease or simply had a history of these disorders. The prevalence of gynecological disease was based on patient reporting while obtaining a history at the initial encounter. It is possible that a history of a gynecological disorder was missed and that the prevalence data may be under-reported. Similarly, not knowing the indications for the high prevalence of hysterectomies in our patient population suggests that patients may have under-reported the prevalence of common gynecological disorders like endometriosis, myomata, and adenomyosis as these conditions are common indications for performing a hysterectomy.

The current investigation is the largest analysis of women with symptomatic PVI and concomitant gynecological disorders. Our data indicate that concomitant gynecological disorders occur infrequently when there is evidence of symptomatic PVI. Patients with a history of endometriosis and PVI demonstrated significant pain reduction with stenting, supporting the concept that PVI is a distinct cause of pelvic pain. Concomitant gynecological disorders should not be a contraindication to treating patients with symptomatic PVI.

None.