Diabetes & Male Reproductive Health Alison M. Rasper, MD Assistant Professor of Urology Division of Reconstructive Urology University of Kentucky Alison.Rasper@uky.edu Second Annual Barnstable Brown Diabetes Center Symposium September 14, 2018

Disclosures Educational consultant for Boston Scientific ™

Objectives Explain the potential impact of metabolic syndrome or diabetes on the reproductive health of both males and females. Describe the use of pharmacologic therapies for the treatment of polycystic ovarian syndrome (PCOS).

Components of Sexual Wellness A state of physical, emotional, mental, and social well- being in relation to sexuality An important and integral aspect of human development and maturation A human right WHO 2006

Erectile Dysfunction Persistent inability to maintain an erection sufficient for intercourse Incidence is age dependent Organic and psychogenic are broad classifications Certain disease states and their treatment are associated with ED

Prevalence in General Population Men aged 40-70 years (N= 1290) No ED (48%) ED (52%) *Massachusetts Male Aging Study. Adapted from Feldman HA, et al. J Urol. 1994;151:54-61.

Prevalence in General Population Epidemiologic analysis from 2126 adult male participants in NHANES Overall prevalence 18.4% = 18 million men in US over age of 20

Causes of Erectile Dysfunction With permission from Goldstein I, and the Working Group for the Study of Central Mechanisms in Erectile Dysfunction. Sci Am. August 2000:70-75.

Prevalence in Diabetic Patients Varies greatly in the literature (20-85%) Meta-analysis of prevalence with 88,577 men (mean age of 55.8): 37.5% Type 1 66.3% Type 2 57.7% both Massachusetts Male Aging study reported 28% age-adjusted prevalence for males with DM compared to 10% without DM Erectile Dysfunction: AUA Guideline (2018) Kouidrat Y. High prevalence of erectile dysfunction in diabetes: a systematic review and meta-analysis of 145 studies. Diabetic Medicine, 2017. 34 (9): 1185—1192.

Diabetes and Erectile Dysfunction In men with diabetes, risk of ED is approximately 3-fold higher than in non-diabetic men ED in men with diabetes is more severe and less responsive to therapy than in men without diabetes Higher chance of progressing to second and third line therapies Walsh et al. 2014

Anatomy Two paired corpora cavernosa (erectile bodies) and a single corpus spongiosum surrounding the urethra, all encased within Buck’s fascia The erectile tissue is comprised of a network of vascular sinusoids surrounded by trabecular smooth muscle.

Mechanism of Erection Blood flow increases secondary to vasodilatation of the cavernosal arteries Relaxation of smooth muscle dilates the lacunar spaces causing engorgement Increased intracorporal pressure expands the trabecular wall against the tunica albuginea Compression of the subtunical veins along with a reduction of venous blood flow results in elevated pressures in the lacunar spaces, “veno-occlusive” mechanism The parasympathetic nervous system provides excitatory input causing vasodilation and erection. (autonomic) The sympathetic nervous system provides input which results in detumescence, maintains flaccidity, and emission. (autonomic) Somatic sensory nerves provide sensation of the penile skin, glans, and urethra. (dorsal nerve). The motor pathway lies within the sacral nerves to the pudendal nerve and innervate the bulbocavernous and ischiocavernous muscles and allow for ejaculation.

Several systems have to work together to produce normal erection. Mechanism of Erection Several systems have to work together to produce normal erection. Initiated in the brain and then has psychological, neurological, hormonal, and blood vessel involvement. Blood flow increases secondary to vasodilatation of the cavernosal arteries Relaxation of smooth muscle dilates the lacunar spaces causing engorgement Increased intracorporal pressure expands the trabecular wall against the tunica albuginea Compression of the subtunical veins along with a reduction of venous blood flow results in elevated pressures in the lacunar spaces, “veno-occlusive” mechanism The parasympathetic nervous system provides excitatory input causing vasodilation and erection. (autonomic) The sympathetic nervous system provides input which results in detumescence, maintains flaccidity,and emission. (autonomic) Somatic sensory nerves provide sensation of the penile skin, glans, and urethra. (dorsal nerve). The motor pathway lies within the sacral nerves to the pudendal nerve and innervate the bulbocavernous and ischiocavernous muscles and allow for ejaculation.

Diabetes & Erectile Dysfunction

Hormonal Changes AUA Guideline 2018: Erectile Dysfunction Morning serum total testosterone levels should be measured New AUA Guideline on Evaluation & Management of Testosterone Deficiency with definition of total testosterone < 300 ng/dL Hypogonadism prevalent in diabetic patient population Consider evaluation & treatment to improve libido, quality of life, depression, complementary ED therapy

Treatment Algorithm for treatment Following thorough history, physical exam, labs Counsel about risk of underlying cardiovascular disease

First-Line Therapy: Oral Agens US Food & Drug Administration (FDA)-approved phosphodiesterase type 5 inhibitors: Viagra (Sildenafil citrate) Levitra/Staxyn (Vardenafil) Cialis (Tadalafil) Avanafil (Stendra) Do not use with nitrates! Ok with stable CAD

Optimize Success Requires sexual stimulation Educate! Dose titration 55% of initial sildenafil non-responders achieved successful results through re-education Dose titration Meal association (empty stomach!) Treat comorbid conditions Preserve endothelial/smooth muscle function (optimize glucose control, reduce smoking, encourage exercise…)

Retrospective review in UK of 5956 men with T2DM Use of PDE5i associated with Lower risk of AMI Lower death from AMI Lower overall mortality [HR 0.54 (0.36- 0.80)]

Second-Line Therapy Vacuum erection device Intracavernosal injection Alprostadil Drug mixture (Trimix: papaverine, phentolamine, alprostadil) Transurethral alprostadil (MUSE)

Third-Line: Penile Implants Third line but: Higher patient and partner satisfaction compared to oral and intracavernosal therapies Satisfaction rates for patients and partners as high as 98% and 96%, respectively These aren’t new! Era began in the late 1960’s with original inflatable device launched by American Medical Systems in 1973

Penile Implant Two companies: Boston Scientific™ (AMS) & Coloplast ® Malleable/semirigid (AMS, Coloplast) Inflatable 2-piece (Ambicor™) 3-piece AMS™ (CX, CXR, LGX) Coloplast® (Titan®)

Complications of Penile Implant Infection (< 3% with newer devices) Mandatory A1c < 9% prior surgery Mechanical Malfunction Regular Wear and Tear Auto – Inflation: decreased new technology Subtle things – under sizing, poor girth, perforation, other organ injury

Summary ED is prevalent in general population and increased in diabetic patients Diabetes can affect psychological, hormonal, vascular, and neurological aspects of erectile function Encourage discussion of sexual health as important for patient and couple health Be willing to change therapy if poor efficacy and urology available for consultation/referral

Questions