The Effects of EDS/HSD in Males: Identifying and Addressing Unique Issues, Needs, and Concerns

The Ehlers-Danlos Society July 10, 2019

Basic assumptions for this webinar (and what happens when you assume?) We assume that males may experience the following features and comorbidities • Reduced proprioception • Weakness in sphincters • Autonomic dysfunction • Pain • Fatigue • Vascular—”stretchier” or fragile blood vessels with dysfunctional valves • Reduced muscle strength with hypotonicity • Most of this webinar will focus on males assigned male at birth and identifying as male (cis-gender male).

The Frustration of Males with EDS/HSD: (summed up in one picture)

$#*!s

*Our thanks to Michael Vash of Vash Designs for giving us permission to use his image)

Why is EDS/HSD diagnosed less in males? Biological factors affecting true incidence and severity

• Hunt • Fight • Move heavy stuff • Achieve erections

To be these manly men doing manly things, males tend to: • be stiff, stable, strong, and well-toned. • have a higher threshold to pain. • produce lots of testosterone • have increased skin thickness • have greater muscle mass • have greater tensile strength in ligaments/tendons

Why is EDS/HSD diagnosed less in males? Underdiagnosis and Misdiagnosis • Less likely to seek healthcare • Common among males • Shame/embarrassment • Blaming selves • May be more likely to be evaluated at a later age when Beighton score no longer “positive” • Provider bias • Needing to “man up” • Pain not taken as seriously • EDS and associated diseases seen as “female diseases”

The effects of EDS/HSD on Male Anatomy

• Testicles • Penis • Prostate • Bladder • Pelvic floor • Rest of the body

Testicles • Autonomic and vascular dysfunction • Higher risk for varicocele and generally dysfunctional blood flow • Decreased size • Reduced testosterone • Treatment of borderline-low testosterone associated with varicocele? • Dysfunctional scrotal retraction • Reduced fertility • Decreased protective factors afforded by testosterone

Penis

• Suspensory ligament laxity • Feel space between pubic bone and penis • Lax skin “hiding” penis • Higher risk of genital infections • Impaired skin integrity • Delayed healing of circumcision? • Priapsm?

Prostate, Bladder, and Pelvic floor

• Increased risk of BPH due to venous reflux? • Preemptive DHT inhibitor (i.e. finasteride)? • Caution with alpha-1 blockers, anticholinergics, and Cialis • Caution with surgical procedures • Consider venous ablasion as alternative to surgical resection? • Chronic prostatitis/LUTS/IC • Weak pelvic floor • PT before antibiotics? Toxicity associate with antibiotics • Feel more comfortable sitting down to urinate

Body

• Skin is thinner, velvety, and may be perceived as less masculine • Shaving can be difficult--skin much thinner underneath • Acne can be painful and cystic due to the thinner skin with levels of androgens higher than in females with acne • Thinner skin can make many treatments especially irritating and painful • Feminine fat distribution--lipedema, cellulite, hormone issues • Gynecomastia from hormone issues? • Poorer muscle size, definition, and tone • Physical activity lack of coordination and other difficulties with physical endurance, sports, strength, etc., • Stretchier vocal cords create a voice with greater cadence--upside singing!

Sexual activity • Fatigue, pain, and difficulty with many common sex positions • With things like POTS, it might be very uncomfortable to be in a position other than supine. • Erectile dysfunction • Is penis vacuum device most effective? • Venous procedures? • Ejaculation disorders • Retrograde ejaculation • Anorgasmia • Higher risk for abrasions • Higher risk for STDs

LGBTQI concerns

• Reemphasize condom use and consider PrEP (Truvada). • Explain the consequences of STDs other than HIV (currently, regular condom use may be decreased due to PrEP and recent studies confirming that it cannot be transmitted by a virally suppressed person). • Also, consider the effects of Truvada on bone mineral density and mitochondria. • Consider sexual practices of increased frequency and potential adverse effects on rectal health and TMJ function. Already increased risk rectal prolapse TMJ dysfunction from stretching jaw for oral sex? • Transgender males/females--effects of hormonal therapy and the syndrome on their transition • Non-binary individuals • Intersex individuals *Be mindful of anti-LGBTI bias, discrimination, and maltreatment both currently and historically in medicine.

Effects of meds and other treatments

• Effects of antidepressants • Effects on ejaculation • Effects of erectile dysfunction meds • vasodilators • Effects of prostate meds • Alpha-1 blocker can worsen autonomic dysfunction (opposite of midodrine) • Hormonal effects of Reglan • Increased prolactin • Effects of Rogaine • Vasodilation from systemic absorption through thinner scalp skin

Implications for the healthcare team:

• The syndrome could cause distress for those assigned as males at birth and having a congruent gender identity. • Traditional gender roles • Secondary sex characteristics may be perceived as more feminine. • Poorer athletic ability • Let them know what could be expected vs. expecting them to tell you • This could be especially important for adolescents and during puberty • Let them know it's the disease and not their own fault • Advising more exercise may have a more significant connotation for males who include athletic achievement in definition of masculinity. Give realistic expectations. DO NOT CONSIDER SEX/GENDER WHEN EVALUATING FOR EDS/HSD AND ASSOCIATED COMORBIDITIES

Will Environmental Factors Increase the Rate of Diagnosis and/or Severity for EDS/HSD in Males?

• Studies show decreasing testosterone levels globally • Increased adiposity increases estrogen levels through aromatase • Environmental estrogens • Sedentary lifestyle • Changing societal attitudes about gender • Greater awareness

References

• Adib, N., Davies, K., Grahame, R., Woo, P., & Murray, K. (2005). Joint hypermobility syndrome in childhood. A not so benign multisystem disorder? Rheumatology (Oxford, England), 44(6), 744–750. https://doi.org/10.1093/rheumatology/keh557 • Baio J, Wiggins L, Christensen DL, et al. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. MMWR Surveill Summ 2018;67(No. SS-6):1–23. DOI: http://dx.doi.org/10.15585/mmwr.ss6706a1 • Baeza-Velasco, C., Cohen, D., Hamonet, C., Vlamynck, E., Diaz, L., Cravero, C., … Guinchat, V. (2018). Autism, Joint Hypermobility-Related Disorders and Pain. Frontiers in Psychiatry, 9, 656. https://doi.org/10.3389/fpsyt.2018.00656 • Bosson, J., Michniewicz, K., & Bosson, J. (2013). Gender dichotomization at the level of ingroup identity: What it is, and why men use it more than women. Journal of Personality and Social Psychology, 105(3), 425–442. https://doi.org/10.1037/a0033126 • Castori, M., Camerota, F., Celletti, C., Grammatico, P., & Padua, L. (2010). Ehlers–Danlos syndrome hypermobility type and the excess of affected females: Possible mechanisms and perspectives. American Journal of Medical Genetics Part A, 152(9), 2406–2408. https://doi.org/10.1002/ajmg.a.33585 • de Jong, Y., Pinckaers, J., ten Brinck, R., Lycklama à Nijeholt, A., Dekkers, O., & Phillips, R. (2014). Urinating Standing versus Sitting: Position Is of Influence in Men with Prostate Enlargement. A Systematic Review and Meta-Analysis. PLoS ONE, 9(7), e101320. https://doi.org/10.1371/journal.pone.0101320 • Gat, Y., & Goren, M. (2018). Benign Prostatic Hyperplasia: Long-term follow-up of prostate volume reduction after sclerotherapy of the internal spermatic veins. Andrologia, 50(2), n/a–n/a. https://doi.org/10.1111/and.12870 • Centola, G., Lee, K., & Cockett, A. (1987). Relationship between testicular volume and presence of varicocele: A comparative study. Urology, 30(5), 479–481. https://doi.org/10.1016/0090-4295(87)90386-4 • Hsu, G., Hsieh, C., Wen, H., Hsu, W., Wu, C., Fong, T., … Tseng, G. (2004). Anatomy of the Human Penis: The Relationship of the Architecture Between Skeletal and Smooth Muscles. Journal of Andrology, 25(3), 426–431. https://doi.org/10.1002/j.1939-4640.2004.tb02810.x • Ji, B., & Jin, X. (2017). Varicocele is associated with hypogonadism and impaired erectile function: a prospective comparative study. Andrologia, 49(6), . https://doi.org/10.1111/and.12683 • Kurbatov, D., Kuznetsky, J., & Traish, A. (2008). Testosterone improves erectile function in hypogonadal patients with venous leakage. Journal of Andrology, 29(6), 630–637. https://doi.org/10.2164/jandrol.108.005264

• Li, C., Agrawal, V., Minhas, S., & Ralph, D. (2007). The penile suspensory ligament: abnormalities and repair. BJU International, 99(1), 117–120. https://doi.org/10.1111/j.1464- 410X.2007.06551.x • Giacomoni, P., Mammone, T., & Teri, M. (2009). Gender-linked differences in human skin. Journal of Dermatological Science. Elsevier Ireland Ltd. https://doi.org/10.1016/j.jdermsci.2009.06.001 • Glidden, V., Mulligan, L., Mcmahan, P., Anderson, G., Guanira, M., Chariyalertsak, M., … Grant, M. (2017). Brief Report: Recovery of Bone Mineral Density After Discontinuation of Tenofovir-Based HIV Pre-exposure Prophylaxis. JAIDS Journal of Acquired Immune Deficiency Syndromes, 76(2), 177–182. https://doi.org/10.1097/QAI.0000000000001475 • Goren, M., & Gat, Y. (2018). Varicocele is the root cause of BPH: Destruction of the valves in the spermatic veins produces elevated pressure which diverts undiluted testosterone directly from the testes to the prostate. Andrologia, 50(5). https://doi.org/10.1111/and.12992 • Grahame, R. (2017). The multisystemic nature and natural history of joint hypermobility syndrome and Ehlers–Danlos syndrome in children. Rheumatology, 56(12), 2048–2049. https://doi.org/10.1093/rheumatology/kex241 • Moldwin, R. (2002). Similarities between interstitial cystitis and male chronic pelvic pain syndrome. Current Urology Reports, 3(4), 313–318. https://doi.org/10.1007/s11934-002- 0056-x • Morlino, S., Dordoni, C., Sperduti, I., Venturini, M., Celletti, C., Camerota, F., … Castori, M. (2017). Refining patterns of joint hypermobility, habitus, and orthopedic traits in joint hypermobility syndrome and Ehlers–Danlos syndrome, hypermobility type. American Journal of Medical Genetics Part A, 173(4), 914–929. https://doi.org/10.1002/ajmg.a.38106 • Padoa, A., & Rosenbaum, T. (2016). The Overactive Pelvic Floor (1st ed. 2016.). Cham: Springer International Publishing. https://doi.org/10.1007/978-3-319-22150-2 • Rebonato, A., Auci, A., Sanguinetti, F., Maiettini, D., Rossi, M., Brunese, L., … Torri, T. (2014). Embolization of the Periprostatic Venous Plexus for Erectile Dysfunction Resulting from Venous Leakage. Journal of Vascular and Interventional Radiology, 25(6), 866–872. https://doi.org/10.1016/j.jvir.2014.01.015 • Rew, L., Young, C., Harrison, T., & Caridi, R. (2015). A systematic review of literature on psychosocial aspects of gynecomastia in adolescents and young men. Journal of Adolescence, 43, 206–212. https://doi.org/10.1016/j.adolescence.2015.06.007 • Stern, C., Pepin, M., Stoler, J., Kramer, D., Spencer, S., & Stein, C. (2017). Musculoskeletal Conditions in a Pediatric Population with Ehlers-Danlos Syndrome. The Journal of Pediatrics, 181, 261–266. https://doi.org/10.1016/j.jpeds.2016.10.078 • Troy Blackburn, J., Bell, D., Norcross, M., Hudson, J., & Engstrom, L. (2009). Comparison of hamstring neuromechanical properties between healthy males and females and the influence of musculotendinous stiffness. Journal of Electromyography and Kinesiology, 19(5), e362–e369. https://doi.org/10.1016/j.jelekin.2008.08.005