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

2. Disclosures
Educational consultant for Boston Scientific ™

3. 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).

4. 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

5. 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

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

7. 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

8. 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.

9. 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, (9): 1185—1192.

10. 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

11. 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.

12. 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.

13. 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.

14. Diabetes & Erectile Dysfunction

15. 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

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

17. 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

18. 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…)

19. 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 ( )]

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

21. 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

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

23. 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

24. 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

25. Questions