1. Sexual Dysfunction in IBD: Case Studies Raymond Cross, MD, MS, AGAF Associate Professor of Medicine Director, IBD Program University of Maryland School of Medicine

2. Raymond Cross, MD, MS, AGAF Disclosures Abbvie: Advisory Committees or Review Panels, Consulting,, Grant/Research Support Janssen: Advisory Committees or Review Panels, Consulting, Grant/Research Support Takeda: Advisory Committees or Review Panels, Grant/Research Support

3. Case Presentation #1 17 year old with UC involving the entire colon. Diagnosed at age 15 after developing bloody diarrhea. Treated with mesalamine without improvement. Treated with prednisone with resolution of symptoms; however unable to remain off of steroids due to recurrent symptoms.

4. Case presentation (cont.) 1 year after diagnosis started on mercaptopurine but unable to decrease need for steroids (6 TGN 325). IFX 5 mg/kg given at weeks 0, 2, and 6; however hospitalized after 2 nd dose for a flare of colitis requiring IV steroids. Despite increasing the dose of IFX to 10 mg/kg he cannot taper steroids and eventually loses response to high dose steroids.

5. Case presentation (cont.) He undergoes a subtotal colectomy, followed by proctectomy with IPAA, followed by ileostomy reversal. At his 8 week follow up visit after ileostomy reversal, he has good pouch function but reports difficulty getting and maintaining an erection.

6. Case presentation #2 46 year old man with indeterminate colitis with mild gastrointestinal symptoms despite normal inflammatory markers and a normal colonoscopy. Reports intermittent difficulty getting an erection. PMH: GERD, osteoarthritis, recurrent MRSA, UE DVT, juvenile polyposis syndrome, OSA, osteoporosis

7. Case presentation (cont.) PSHx: Right hemicolectomy 2004 Meds: Alendronate 70 mg weekly; cholecalciferol 5000 units daily; celecoxib 200 mg bid; duloxetine 60 mg daily; azathioprine 150 mg daily; adalimumab 40 mg weekly; fexofenadine- pseudophedrine daily; metoprolol 25 mg bid; pantoprazole 40 mg bid; ranitidine 150 mg daily SH: Former smoker (0.5 ppd, quit 2004); 1 ETOH drink per week; no illicit drugs; married

8. How common is sexual dysfunction in men? How common is sexual dysfunction in men with IBD? What are the most common disorders in men? What clinical factors are associated with sexual dysfunction?

9. Prevalence of Sexual Dysfunction in the General Population 31% of men report sexual dysfunction. Most widely recognized disorders are: – Erectile dysfunction – Diminished libido – Abnormal ejaculation Predictors of sexual distress: – Increasing age – Having a partner – Negative mental state – Poor physical health Laumann, E. O., et al. (1999). Jama; Feldman, H. A., et al. (1994). J Urol; Brotto, L. A., et al. (2010). Journal of Sexual Medicine

10. Factors Associated with Impairments in Sexual Desire and Arousal Active luminal or extraintestinal manifestations Surgery Medications Anxiety and depression Distorted body image Age-related changes Hormonal changes Other psychological factors (Deliberate infertility, financial reasons, divorce/separation caused by the disease) Ghazi, LJ. et al. Inflamm Bowel Dis. In press

11. Medications and Conditions Commonly Associated with ED Cardiovascular and vascular disease Anti-hypertensives (clonidine, methyldopa, thiazide diuretics) Narcotics Selective serotonin reuptake inhibitors (SSRI) Neurologic disorders Diabetes and other endocrine disorders (thyroid, low “T”) Alcoholism Depression Other drugs (ketoconazole, spironolactone, cimetidine, MTX) Bicycling Ghazi, LJ. et al. Inflamm Bowel Dis. In press

12. Sexual Interest and Satisfaction in Patients with IBD Sexual satisfaction affected in 80% of patients with active IBD. – “Quite a bit” or “very much” in 1/3 Men had higher interest and satisfaction than women. Active perianal disease, increasing disease activity, fatigue, anxiety, and depression associated with lower interest and satisfaction. Kappelman, M., et al. (2012). Inflammatory Bowel Diseases 18: S43-S44.

13. Sexual Function by Gender in Patients with IBD ScaleMean (SD) IBD Cohort Mean (SD) Cancer Cohort Mean (SD) Non-cancer Cohort Overall SFQ score (men) 3.84 (0.9)3.23 (1.24)3.93 (0.80) Overall SFQ score (women) 2.53 (1.02)2.62 (1.28)3.33 (1.03) Hagan, M. et al. ACG 2014  11% of men were not sexually active.  IBD had a negative impact on sex in 20% of men.  20% of men experience erectile dysfunction.

14. Sexual Function Men with IBD 36% of men report having “a lot” or “quite a bit” of sex in preceding month 44% of men with moderate to severe disease activity felt severely compromised sexually Erectile function was impacted by disease activity (OR 2.5) Men in remission or with mild activity had normal erectile function Depression negatively influence satisfaction with sex (OR 2.3) Only 25% of patients wanted to discuss sexuality with provider Timmer, A., et al. (2007). Inflamm Bowel Dis; Timmer, A., et al. (2007). Clin Gastroenterol Hepatol.

15. How common is sexual dysfunction after surgery in men?

16. Gender Differences in Surgical Outcomes in UC Prospective study of UC patients undergoing proctectomy (n=66) – 48 IPAAs and 18 end ileostomies Men reported improved erectile function, sexual function, disease-specific and general QoL Women reported improved sexual desire, and disease-specific and general QoL No gender specific differences from baseline to follow up Wang, J. Y., et al. (2011). Dis Colon Rectum

17. Functional Results and QoL after IPAA Fazio VW, et al. Ann Surg 1995 Sexual function evaluated in 626 patients 18 years of age or older after IPAA 19 patients had sexual limitations – Retrograde ejaculation (n=8) – Decreased libido (n=4) – Impotence (n=1) – Dyspareunia (n=6) Decreased sexual function in 12% of patients with CD

18. Sexual Function after IPAA 1386 patients with IPAA for CUC between 1981 and 1994 Before surgery 16% and 20% of patients reported no or reduced sexual activity After IPAA 25% reported improved quality of sex life, 56% reported no change, 16% reported mild restriction, and 3% reported severe restriction 10 years after IPAA, no or retrograde ejaculation in 3% Farouk, R., et al. (2000). Ann Surg

19. Evaluation and Treatment of Sexual Dysfunction in Men Ask men if they have problems with sexual function! Control Disease Activity Identify and treat concurrent depression and anxiety Identify and treat cardiovascular disease Refer to urology for medical, injection and surgical treatment * * Check T

20. Treatment of Sexual Dysfunction in Men Identify the underlying etiology Identify and treat cardiovascular risk factors 1 st line medical therapy is phosphodiesterase-5 inhibitors (sildenfil, vardenafil, tadalafil, and avanafil) – Do not use nitrates with PDE-5 inhibitors – May use stable dose of alpha adrenergic blocker 2 nd line therapies: penile self-injectable drugs; intraurethral alprostadil; vacuum devices 3 rd line therapies: penile implant Replace testosterone only with hypogonadism