Introduction
Vascular malformations (VM) are developmental anomalies of veins, arteries, capillaries, and/or lymphatics which may occur sporadically in isolation or in association with recognized syndromes, including Klippel-Trenaunay Syndrome (KTS), Congenital Lipomatous Overgrowth Vascular malformations, Epidermal nevi Scoliosis/skeletal and spinal Syndrome (CLOVES), Generalized Lymphatic Anomaly, and Gorham Stout Disease (ISSVA Classification of Vascular Anomalies 2018 International Society for the Study of Vascular Anomalies, www.issva.org). VM are distinct from vascular tumors, another category of vascular anomalies that includes hemangiomas. The overall prevalence of VM in the United States has been estimated at 1.5% of the general population, and these patients may experience functional impairment, chronic pain, psychological stress, infection, and in rare cases, death from bleeding or embolism.1
Involvement of the genitourinary (GU) tract in males with VM is uncommon. In one retrospective single institution series of 3889 male patients with vascular anomalies seen between 1995 and 2010, genital involvement by any vascular anomaly occurred in only 117 patients (3%).2 This included patients with infantile hemangiomas (n = 10), Kaposiform Lymphatic Anomaly (n = 2), lymphatic malformations (n = 46), venous malformations (n = 33), and capillary- venous-lymphatic malformations (n = 16). Another retrospective report of males and females with KTS seen between 1970 and 2005 suggested that as many as 30% of individuals with this disorder have GU involvement.3 This study did not provide details of sexual function or fertility, but did report instances of hematuria and erectile dysfunction. Anecdotal experience from our multidisciplinary VM clinics also suggests that GU VM can impact the physical and psychosocial well-being of older boys and men, and also may be of concern to parents of minors with these malformations.
We hypothesized that males with VM involving the GU tract and pelvis would have a high prevalence of symptoms of sexual dysfunction and sexual dissatisfaction, and that these issues would be more common than in males with VM at other locations.
Materials and methods
Subjects
Eligible participants included 709 males 18 years of age or older and parents/guardians males younger than age 18 years in the United States who were members of 1 of 3 patient and family VM support groups. The KT support group (http://k-t.org/) database included 424 eligible members. The CLOVES Syndrome Community (https://clovessyndrome.org/) included 200 eligible members. The Lymphangiomatosis & Gorham’s Disease Alliance (https://www.lgdalliance.org/) had 85 eligible members.
Surveys
A survey was designed by the authors based on questions from the validated Patient-Reported Outcomes Measurement Information System (PROMIS) – Sexual Function and Satisfaction v2.04 and the International Index of Erectile Function5 surveys. The survey was assembled using software by Qualtrics (Seattle, WA and Provo, UT). The survey is presented in its entirety in the Supplemental Digital Appendix 1 (https://links.lww.com/JV9/A30). The survey was targeted to adult males with VM; a branch point in the survey asked parents of minor males identical questions about their sons’ reproductive and sexual function to the best of their knowledge. Surveys asked about sexual interest, sexual function, and sexual satisfaction. Subjects were asked whether they had fathered children, either through intercourse or artificial insemination, and whether fertility was a concern. Free-text response space was provided for additional comments related to each question. The survey included 105 yes/no or brief Likert scale questions (almost never = 1, a few times [much less than half] = 2, sometimes [about half] = 3, most of the time [much more than half] = 4, almost always or always/5). A single question (#40) had 6 options (almost never = 1, a few times [much less than half] = 2, sometimes [about half] = 3, most of the time [much more than half] = 4, almost always = 5, always = 6). For sexual symptoms, a response of “at least half of the time”) was considered substantial. Demographic information was requested including patient age, specific VM diagnosis, and whether the diagnosis had been corroborated by a physician affiliated with a dedicated VM clinic. Details of the anatomic location(s) of the VM with specific descriptions of GU involvement (such as scrotum or penis) also were requested. The required time necessary to complete the entire survey was estimated to be 15 minutes.
The Institutional Review Board for the University of North Carolina School of Medicine approved this study and waived the requirement for informed consent. Surveys were distributed electronically by participating VM support group directors either to all group members or to males over age 18 years and parents of males under age 18. The survey link was also shared on organizational social media sites and in several newsletters. Recipients were given 2 months to respond, at which time a repeat email was sent out by the support group. An additional month was then allowed for additional responses before tallying results.
Data collection and analysis
Completed survey responses were reviewed. An attempt was made to look at responses to each of the questions in the survey by subject age, specific VM diagnosis, and the specific anatomic GU involvement. For questions with numeric answers (Likert scale questions), univariate differences between responses for subjects with or without GU involvement by a VM was assessed using Student t tests.
Results
Survey responses were received from 49 individuals of 709 support group members (6.9%). Seven respondents were excluded from the study due to reported age <18 years (not submitted by a parent or guardian). Therefore, 42 respondents were included in the evaluation. This included 27 of 424 (7%) from the KT support group, 7 of 200 (3.5%) from the CLOVES support group, and 8 of 85 (9.4%) from the Lymphangiomatosis & Gorham’s Disease Alliance. Respondents ranged in age from 21 to 73 years (median 44 years). An additional 2 responses were submitted by parents of minors (or delayed older child) in these groups, ages 15 and 18 years.
Thirty-three of the 42 respondents (79%) reported that their VM involved the GU tract and/or pelvis including the penis (n = 11), scrotum/testicles (n = 25), anus (n = 8), buttocks (n = 14), lower abdomen (n = 10), or inner thighs (n = 17; Table 1). Several patients had involvement of more than one of these areas and are counted in multiple groups. All of the 33 patients with such involvement endorsed that they had venous malformations or capillary-venous-lymphatic malformations, as did the 9 respondents whose VM did not involve the GU tract or pelvis. Among subjects with GU/pelvic involvement, 17 of 33 (51.5%) reported symptoms (Table 1). These included pain with masturbation (n = 2), pain with intercourse (n = 8), bleeding with masturbation (n = 2), bleeding with sexual intercourse (n = 2), lack of interest in sex (n = 15), and erectile dysfunction (n = 8) (Table 2). Some participants reported more than one symptom. Several patients chose to elaborate on these symptoms in the free-text response sections provided. These responses included: “Develop pain in legs/scrotum affected area soon after climaxing”; “My penis only gets partially erect. The first half is fine, exterior part (towards the head) is not”; “When I was able to function sexually, I would bleed from the movement and or any friction. All of my children were born prior to this complication setting in as the disease worsened over the years”; “The vascular flow into my scrotum is increased causing constant pain. I bleed a lot from the area due to swelling from poor lymphatic drainage.” Other free text responses described a lack of sexual symptoms: “No issues, and I have been sexually active for 40 years.”
Table 1. -
Summary of Demographic Information of the Survey Respondents
|
Count |
Percent of Total* |
Genital Involvement |
No Genital Involvement |
| Hemangiomas |
21 |
50 |
18 |
3 |
| Venous |
27 |
64 |
21 |
6 |
| Arteriovenous |
13 |
31 |
13 |
0 |
| KTS |
27 |
64 |
22 |
5 |
| Cloves |
7 |
17 |
7 |
0 |
| Proteus |
0 |
0 |
0 |
0 |
| Other |
4 |
10 |
2 |
2 |
Abbreviation: KTS, Klippel-Trenaunay Syndrome.
*Some patients reported having more than one vascular malformation and are counted within multiple groups. A total of 42 respondents met inclusion criteria for the study.
Table 2. -
Summary of Selected Survey Question Results
| Questions Regarding the Past 30 d |
With Genital Involvement (n = 33) |
Without Genital Involvement (n = 9) |
| Mean |
Standard Deviation |
Mean |
Standard Deviation |
| Sexual interest |
|
|
|
|
| How often have you felt like you wanted to have sexual activity? |
3.52 |
0.85 |
3 |
1.22 |
| How interested have you been in sexual activity? |
3.48 |
1.12 |
2.89 |
1.17 |
| Overall mean |
3.50 |
0.95 |
2.94 |
1.18 |
| Sexual function |
|
| How often were you able to get an erection (get hard) during sexual activity? |
4.38 |
0.88 |
3.86 |
1.46 |
| When you had erections with sexual stimulation, how often were your erections hard enough for penetration? |
4.13 |
1.39 |
3.71 |
1.38 |
| During sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner? |
4.24 |
2.07 |
4.43 |
1.27 |
| How often have you been able to have an orgasm/climax when you wanted to?* |
5.46 |
0.72 |
5.00 |
1.16 |
| Overall mean |
4.44 |
1.23 |
4.25 |
1.20 |
| Sexual satisfaction |
|
| How satisfying have your orgasms or climaxes been? |
5.13 |
0.80 |
4.71 |
1.38 |
| How much pleasure have your orgasms or climaxes given you? |
5.04 |
0.96 |
4.71 |
1.38 |
| How satisfied have you been with your sex life? |
2.80 |
1.42 |
2.44 |
1.42 |
| How much pleasure has your sex life given you? |
3.07 |
1.46 |
2.78 |
1.48 |
| How often have you thought that your sex life is wonderful? |
2.33 |
1.30 |
2.44 |
1.42 |
| How satisfied have you been with your sexual relationship(s)? |
3.13 |
1.81 |
3.78 |
1.99 |
| Overall mean |
3.33 |
1.42 |
3.21 |
1.61 |
| Sexual symptoms |
|
| How often have you had discomfort or pain in your penis or testicles during sexual activity? |
2.00 |
1.12 |
1.43 |
0.54 |
| When you have had sexual activity, how much discomfort or pain have you had in or around your anus or rectum? |
1.32 |
0.80 |
1.00 |
0.00 |
| Overall mean |
1.66 |
0.81 |
1.21 |
0.27 |
|
Questions Regarding the Past 30 d
|
With Genital Involvement
|
Without Genital Involvement
|
|
Yes
|
No
|
Yes
|
No
|
| In the past 30 days, did you have any type of sexual activity? (examples of sexual activity are masturbation, oral sex, and sexual intercourse) |
25 |
7 |
7 |
2 |
| Do you experience pain with masturbation? |
2 |
28 |
1 |
8 |
| Do you experience genital bleeding with masturbation? |
2 |
28 |
0 |
9 |
| Do you experience genital bleeding with sexual intercourse? |
2 |
28 |
1 |
8 |
P values comparing responses for respondents with genital involvement compared to those without were all >0.05.
*Responses for this question were 1–6 instead of 1–5. For the questions in the sexual interest, function, and satisfaction categories, higher scores indicate fewer symptoms. For the sexual symptoms section, higher scores indicate more severe symptoms.
Among subjects without GU involvement, 6 of 9 noted symptoms including pain with masturbation (n = 1), pain with intercourse (n = 1), bleeding with sexual intercourse (n = 2), lack of interest in sex (n = 7), and erectile dysfunction (n = 2). Some respondents reported more than one symptom. There was no significant difference detected between the patients with VM involving the GU tract/pelvis and those with VM only involving other anatomic locations.
Seventeen of 42 respondents (42%) reported having one or more biological children. This included 14 of 33 (43%) who had GU/pelvis involvement and 3 of 9 (33%) who did not. Sixteen of 17 confirmed that this was through natural means. The remaining patient did not confirm whether natural means or artificial insemination was used. One free text response was obtained which reported concerns regarding fertility in a minor patient after surgeries for debulking of VMs: “He had two surgeries to remove them, which supposedly did not affect his testicle. A couple of years ago we collected semen to keep because he was starting new medication which could affect fertility. The clinic said there were no sperms in the material. He handed in material twice and no sperms.”
Discussion
VMs are uncommon and are considered to be rare disorders by the National Organization of Rare Disorders. VM involving the GU tract have been estimated to occur in anywhere from 3% to 30% of patients with VM.2,3 However, the higher reported prevalence rates were reported by a urology group, so that degree of prevalence likely reflected ascertainment bias. That series also included females, and only 5 males with GU involvement.3 The small numbers of patients affected by these rare disorders, the fact that the majority of vascular anomalies clinics in the United States care only for patients under the age of 21 years, and the sensitive nature of the subject matter likely have contributed to the limited information on sexual function and fertility in males with VM involving the GU tract and pelvis. Apart from hematuria,3,6-12 case reports describe painless bleeding with nocturnal erections7 in a 35-year-old man with KTS and a VM involving the penis and scrotum. Another report in the urology literature describes implantation of a penile prosthesis in a man with KTS for management of erectile dysfunction.13
It seems likely that symptoms and concerns related to sexual function, satisfaction, and fertility are more common than has been appreciated in this group of patients. Disappointingly, although our subjects all were voluntary members of dedicated VM support groups, the response rate was only 6.9%. However, 33 of the 42 evaluable respondents reported that their VM involved the GU tract, from a total of 709 members to whom surveys were sent (4.6%). Comparing this prevalence to the reported prevalence of 3% in this population makes it possible that our survey did capture a majority of support group members with VM involving the GU tract.2 Even with this small number of responses, this report has expanded on the types of problems with sexual function which patients may encounter, including difficulty with developing and maintaining erections, penile swelling, and bleeding and pain with masturbation and intercourse but also without sexual activity, though conclusions are difficult to draw from the limited number of responses. While some patients reported experiencing problems with fertility, a sizeable number did report having one or more biologic children by natural means. One patient’s parents also indicated that he had been found to have low sperm counts. Of note and as commented on by one responder, complications of VM may increase with age. Thus, GU-related complaints may worsen over time, underscoring the need for ongoing follow-up of patients as they progress through adulthood.
Surprisingly, concerns about sexual function were not clearly more prevalent in patients with GU tract/pelvic involvement compared with the small number of men with VM at other anatomic locations who responded to the survey. This may be due to the small numbers in this group. However, it also may reflect contributions to sexual function of VM in locations other than the GU tract, possibly due to functional impairment of other body parts, or psychosocial effects of the diagnosis of VM, such as decreased self-esteem. This series focused on males with KTS, CLOVES, and other syndromic VM diagnoses because of their accessibility through support groups. We did not specifically include or exclude males with VM of the central nervous system, face, hands, or other areas which also might be expected to influence self-image and possibly sexual function. Isolated VM involving the GU tract also can occur but such patients likely were not included in the support groups. Lymphedema, another vascular anomaly distinct from lymphatic malformations, also can involve the genitalia with a prevalence in males of under 1%.14 Lymphedema patients were not queried in our study, and could be involved in future studies.
The distributed survey did not include questions regarding the treatment of the respondents’ VMs, including medication use, which could have contributed to some reported symptoms, such as erectile dysfunction. In the urology literature, the most commonly utilized treatments included local vascular compression or surgery, such as gross total resections of bladder VM requiring partial cystectomy.15 In the setting of multidisciplinary vascular anomalies clinics, other treatment options aside from surgery are available to those patients with VM in a variety of anatomic locations, and include image-guided sclerotherapy and medical therapies with drugs such as sirolimus and newer, small molecule therapeutics targeted at genetic mutations such as those involving PIK3CA.
Based on the results of this survey, we conclude that males with VM involving the GU tract/pelvis frequently experience symptoms related to sexual function and satisfaction. Further studies will be needed to confirm the true prevalence and extent of such symptoms in males with VM involving the GU tract and pelvis, as well as with those with VM involving other anatomic locations. In the absence of larger studies, physicians could consider discussion of sexual function, sexual satisfaction, and fertility as part of the care of these patients in the setting of a multidisciplinary vascular anomalies clinic.
Acknowledgments
We would like to thank Dr. Leslie Schover for guiding us in survey design. Special thanks to Kristen Davis (Director, the Cloves Syndrome Community, West Kennebunk, Maine), Mellenee Finger (Director, the KT-Support Group, Milford, Ohio), Lisa Klepper (Director of Patient Programs, Lymphangiomatosis & Gorham’s Disease Alliance, Boca Raton, Florida), and to the vascular malformation support group members who responded to the survey.
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