1. Northwestern Medical Faculty Foundation Sexuality and Bone Marrow Failure Diseases: A Conversation Timothy Pearman, Ph.D. Director, Supportive Oncology Associate Professor Dept. of Medical Social Sciences Dept. of Psychiatry and Behavioral Sciences Feinberg School of Medicine

2. Northwestern Medical Faculty Foundation A caveat: Very little research has been done investigating sexual dysfunction in bone marrow failure diseases “Bone marrow failure sexual function” (3 references on PubMed vs. 6164) Most research has been done either in cancer, cardiovascular or in stem cell transplant survivors Therefore, some speculation is necessary

3. Northwestern Medical Faculty Foundation What factors impact sexual functioning?

4. Northwestern Medical Faculty Foundation I. Age and sexual function Age impacts sexual functioning in both males and females Males Erectile dysfunction increases with age ED increases with comorbid medical conditions (diabetes, CVD, etc.) Females Menopausal impact on sexual functioning (vaginal dryness, decreased libido, dyspareunia)

5. Northwestern Medical Faculty Foundation I. Age Sexual functioning decreases with age independent of bone marrow failure Difficult to determine relative impact of age vs. hematologic abnormalities vs. treatment

6. Northwestern Medical Faculty Foundation Massachusetts Male Aging Study: Key Prevalence Study of ED

7. Northwestern Medical Faculty Foundation Major Risk Factor for Sexual Dysfunction: Aging

8. Northwestern Medical Faculty Foundation Female sexual dysfunction Post-menopausal changes can lead to dysfunction Incidence in cancer survivors: 30-100% This, despite the fact that overall QOL is quite good in female cancer survivors

9. Northwestern Medical Faculty Foundation Medical Factors Medications Narcotics, disease-specific medications Chronic disease CAD, HTN, Dyslipidemias, PVD and depression Lifestyle Alcohol/Drug abuse Stress Smoking

10. Northwestern Medical Faculty Foundation III. Medications Antihypertensives/diuretics Selective serotonin-reuptake inhibitors (antidepressants) Hormonal agents (e.g., antiandrogens) Cytotoxic agents H 2 antagonists

11. Northwestern Medical Faculty Foundation II. Major Risk Factors for Dysfunction: Chronic Disease Risk Multiplied* Diabetes 4.1 Prostate disease 2.9 Peripheral vascular disease2.6 Cardiac Problems1.8 Hyperlipidemia1.7 Hypertension1.6 *Age-adjusted odds ratio.

12. Northwestern Medical Faculty Foundation IV. Lifestyle Alcohol, drug use Inactivity/Deconditioning Smoking Stress

13. Northwestern Medical Faculty Foundation High risk populations Young Old Hematologic (malignancies)

14. Northwestern Medical Faculty Foundation Young Very little research has investigated the impact of childhood/adolescent treatment on sexual functioning (just fertility) Many survivors will not go through puberty without hormonal treatment Role of testosterone replacement unclear (Greenfield et al., 2010) 45% report sexual dissatisfaction (Barrera et al., 2010)

15. Northwestern Medical Faculty Foundation Hematologic (malignancies) Few studies have looked extensively at sexual functioning Men function better than women 25-30% report sexual dysfunction attributed to diagnosis High risk of ED, decreased orgasm in men >50% report dissatisfaction with sexual functioning GVHD can cause penile curvature, pain and ED

16. Northwestern Medical Faculty Foundation Undertreatment Numerous reasons Only 14% of patients reported being asked about sexual issues by their physicians (Pfizer Global Study of Sexual Attitudes and Behaviors, 2011) Thoughts? Provider driven? Patient driven?

17. Northwestern Medical Faculty Foundation Undertreatment 71%: “ MD would dismiss the issue.” 68%: “MD would be embarrassed.” 74%: “No therapy available. “I should focus on my illness and not on sexual activity/health..”

18. Northwestern Medical Faculty Foundation Screening Few screenings are common in clinical practice Importance of simply asking NCCN guidelines recommend systematic evaluation and treatment Patients/family members, in general, are more comfortable talking about this than you would imagine (if only the same were true for treatment providers!)

19. Northwestern Medical Faculty Foundation Recommendations for treatment providers Discuss pretreatment sexual status Provide information about possible sexual changes before treatment Make use of appropriate posttreatment psychological, pharmacologic and mechanical sexual aids 5 A’s: ask, advise, assess, assist, arrange follow up (Sadovsky et al., 2010)

20. Northwestern Medical Faculty Foundation Classification of ED: Psychogenic or Organic? PsychogenicOrganic Sudden onsetGradual onset Complete immediate lossIncremental progression AM erections presentLack of AM erections Varies with partner andLack of erections; situationlittle variation

21. Northwestern Medical Faculty Foundation Psychogenic Causes of Sexual Dysfunction

22. Northwestern Medical Faculty Foundation Organic Causes of Sexual Dysfunction

23. Northwestern Medical Faculty Foundation Why Discuss Sexual Health? Treating this issue improves: Quality of life Patient satisfaction Patient-clinician relationships Sadovsky R et al, Cancer and Sexual Problems, J Sex Med, 2010; 7: 349-373

24. Northwestern Medical Faculty Foundation Step-Care Approach Men: first line therapy Life style/medication modification Counseling (Depression, body-image issues, anxiety) For ED: Androgen replacement if patient hypogonadal Oral therapy (PDE-5 Inhibitors)

25. Northwestern Medical Faculty Foundation Step-Care Approach Women: first line therapy Sex therapy: focus not only on sexuality, but intimacy Vaginal estrogen Cream, ring or tablet Vaginal moisturizers (Replens, RepHresh)

26. Northwestern Medical Faculty Foundation First-Line Therapy: Medication Modifications Modify drug regimens associated with ED Antihypertensives/diuretics Narcotics Selective serotonin-reuptake inhibitors Hormonal agents (e.g., antiandrogens)  Consider Intermittent Androgen Ablation Therapy H 2 -receptor antagonists

27. Northwestern Medical Faculty Foundation Step-Care Approach Women: first line therapy Vaginal estrogen Cream, ring or tablet Increases in serum estrogen Clinical significance unclear Vaginal moisturizers (Replens, RepHresh) Again, clinical significance unclear

28. Northwestern Medical Faculty Foundation Step-Care Approach to ED Management First Line Therapy Life style/medication modification Counseling Androgen replacement Oral therapy (PDE-5 Inhibitors)

29. Northwestern Medical Faculty Foundation First-Line Therapy: Oral PDE-5 Inhibitors Phosphodiesterase type-5 (PDE-5) inhibitors Sildenafil - Viagra Tadalafil - Cialis Vardenafil - Levitra

30. Northwestern Medical Faculty Foundation Optimizing PDE-5 Inhibitor Therapy Incorrect use/treatment failure Patients should be advised Sexual stimulation is needed A number of drug trials may be required Sildenafil, Vardenafil may be taken with food but onset of action may be delayed Risk factor modification may improve treatment outcomes Follow-up visits are essential

31. Northwestern Medical Faculty Foundation Second-Line Therapy for Management of ED Vacuum constriction device Intracavernosal injection Alprostadil Drug mixture* (trimix: papaverine, phentolamine, alprostadil) Transurethral alprostadil (MUSE ® ) Topical therapy–creams/gels

32. Northwestern Medical Faculty Foundation Vacuum Constriction Device

33. Northwestern Medical Faculty Foundation Third-line Therapy: Penile Prostheses Intolerance or lack of response to other treatment modalities Irreparably damaged erectile tissue Specific concomitant medical conditions such as vascular or neurological disease, chronic renal disease, and genital trauma (e.g., Peyronie’s disease) >85% would undergo surgery again and/or recommend procedure to a friend (n=178)

34. Northwestern Medical Faculty Foundation What can I do to help my partner?? Normalize physical response to treatment Encourage open communication with partner Include nongenital foreplay to minimize performance pressure

35. Northwestern Medical Faculty Foundation What can I do?? Include sexual aids in the bedroom Focus on pleasure/arousal rather than orgasm to limit performance pressure Use sexual positions that are physically easiest Encourage brief course of sex therapy with professional

36. Northwestern Medical Faculty Foundation Psychotherapy Discussion of sex after menopause/older age Managing vaginal dryness Managing ED Sensate focus Communication issues Lifestyle modification: alcohol, smoking, exercise

37. Northwestern Medical Faculty Foundation What can I do?

38. Northwestern Medical Faculty Foundation What can I do? Exercise is the most strongly supported behavioral intervention for fatigue (Mishra et al., 2012) Impact on fatigue, sleep, mood, quality of life, physical functioning Surgeon General recommends 30 min moderate activity most days Consult with physician and/or physical therapist

39. Northwestern Medical Faculty Foundation Benefits related to sex Changes in body composition Increased self esteem Decreased fatigue Decreased risk of comorbid conditions Decreased depression, anxiety Increased quality of life Increased desire (Cormie et al., 2013)

40. Northwestern Medical Faculty Foundation

41. Yoga Look for churches, community centers, senior centers that offer beginners’ yoga Modifiable based on physical challenges, other medical conditions, premorbid physical activity level

42. Northwestern Medical Faculty Foundation Partner yoga!

43. Northwestern Medical Faculty Foundation

45. Sleep Hygiene & Sleep Routines Avoid caffeine after noon Within 2 hours of bedtime avoid: Tobacco/nicotine Alcohol Exercise Heavy Meals  Stimulus control  15-20 minute intervals  Bedroom rule of two

46. Northwestern Medical Faculty Foundation Conclusions Sexual functioning is an important quality of life issue for many patients. Sexual dysfunction is highly prevalent and age is a leading risk factor Hematologic disease states and treatment can cause or exacerbate impaired sexual functioning. Treatment algorithm is goal-directed, stepwise

47. Northwestern Medical Faculty Foundation Interventions (cont.) Overall, interventions work better if include education, self-efficacy, motivation components In general, psychological interventions are feasible and seem to work well (Brotto, Yule & Brecken, 2010) Exercise, sleep can contribute to sexual health