While the cancer patient may be affected by sexual dysfunction throughout the entire course of the disease, sexual health is largely underevaluated and undertreated. Sexual problems should be anticipated and patients should be actively screened as they are unlikely to initiate discussion on sexual issues. Cancer-related sexual dysfunction may involve several components, and an understanding of the underlying etiologies is essential to tailoring the appropriate treatment to the individual patient. This article reviews the numerous factors potentially involved in male sexual dysfunction associated with a variety of cancers.
Cancer is a major health concern with a profound impact on quality of life and sexual function. It is estimated that in the year 2005 a total of 710,040 new cancer cases will be diagnosed among American men, 312,660 new cancer cases will involve the male genitourinary system, and prostate cancer, being the most prevalent, will affect 232,090 men (33% of all estimated new cancer cases among males). Sexual dysfunction in cancer patients is multifactorial and involves many different domains, related to both psychological and physiologic insults; erectile dysfunction (ED) is only one of these potential injuries. Unfortunately, oncologists and urologists tend to address only ED in cancer patients and overlook other aspects of sexual dysfunction such as loss of sexual desire, disorders of ejaculation, orgasmic dysfunction, and body image issues.
An Undertreated Problem
While the cancer patient may be affected by sexual dysfunction throughout the entire course of the disease, from the first stage of diagnosis through treatment and cure or progressive disease, sexual health is largely underevaluated and undertreated. Incrocci et al demonstrated a significant decline in patients’ self-reported sexual activity-attributed to decreased sexual desire and interest, erectile dysfunction, or a partner’s loss of sexual desire-among men diagnosed with localized prostate cancer awaiting definitive treatment. Despite the use of questionnaires 4 to 9 weeks after the diagnosis was made and treatment modality determined (baseline sexual function being based on patient recall), this innovative study emphasizes the impact of the diagnosis of cancer itself on sexual function. The authors concluded that sexual health should be discussed with cancer patients early in the course of treatment, as part of a comprehensive oncologic approach.
Sexual problems should be anticipated and patients should be actively screened as they are unlikely to initiate discussion on sexual issues, believing that it is inappropriate to address sexual health when curing cancer should be the main concern. Even if sexual health issues are not present, early discussion will legitimize raising sexual issues later in the course of the treatment or the disease.
Litwin et al compared health-related quality of life (HRQOL) as assessed by the physician and as reported by prostate cancer patients, and demonstrated a gross underestimation of the prevalence of symptoms by clinicans. In fact, they found that underestimation of all domains of quality of life including sexual function (libido and ED) was the rule when reported by the urologist. Ananth et al demonstrated that sexual dysfunction is more profound in patients with advanced cancer receiving palliative care, affecting the frequency of sexual relations and sexual satisfaction. Notwithstanding, cancer patients attending either palliative care or general oncology clinics were more willing to discuss their sexual lives with a professional, compared to healthy controls. With currently available treatment modalities (as curing cancer or achieving a long-term remission is not uncommon), patients may face sexual ill health and its burden on quality of life long after cancer treatment has been completed.
The discomfort level that clinicians exhibit in the evaluation and treatment of sexual health issues is not confined to the cancer setting. By some estimates, only 14% to 35% of patients ever get asked about sexual health by the family physician. This problem is deep-seated and rooted in the inadequate training that medical students and residents receive in sexual health evaluation and management.
Etiology of Sexual Dysfunction in Cancer Patients
Cancer-related sexual dysfunction may involve several different components, and an understanding of the underlying etiologies is essential to tailoring the appropriate treatment to the individual patient.
In the early stages of cancer diagnosis and treatment, patients may confront feelings of depression, fear of death or of treatment consequences, apprehension of imminent erectile dysfunction, deterioration of self-esteem, or impairment of a long-lasting emotional and sexual balance with their spouse.[6,7] Both patient and spouse may experience difficulties in discussing sexual relationship issues, feeling that it is not appropriate when confronting cancer. Libido is adversely affected from the initial steps of diagnosis and treatment planning, and sexually oriented thoughts and desire, if they exist, may result in feelings of guilt and further suppression of sexuality. Cancer treatment, especially if it leads to changes in physical appearance (eg, alopecia, stomas), may exert further psychological stress with impairment of body image and loss of one’s perceived sexual attractiveness.
Treatment-related erectile dysfunction may perpetuate loss of self-esteem and sense of manhood if left untreated, and early comprehensive diagnosis and intervention of sexual dysfunction is the goal. Patients may experience fears-often unrealistic-of potential harm to themselves or their partner during sexual activity, especially when cancer treatment is ongoing. Patients should be encouraged to discuss their fears and other sexual issues with their partners and with professionals and to resume sexual activity soon after cancer treatment, if feasible.
Cancer is accompanied by physical symptoms, which may adversely affect sexual function. General symptoms include fatigue, gastrointestinal symptoms (nausea, diarrhea), urinary tract symptoms, sleep disorders, and pain. Surgical treatment, chemotherapy, radiation therapy, combined-modality treatment, and biologic and hormonal therapies may all exacerbate physical symptoms. Uncontrolled symptoms impair all aspects of sexual function including sexual interest, sexual desire, and erectile function and cannot be left untreated if sexual dysfunction is to be successfully managed.
Drug-Induced Sexual Dysfunction
While physical symptoms may induce sexual dysfunction in cancer patients, symptom control may be further complicated by the adverse effect of drugs on sexual function. Chronic opioid consumption to control pain in cancer patients has been demonstrated to induce hypogonadism in males and further exacerbate depression, fatigue, and sexual ill health.[9,10] Treatment of depression and anxiety in cancer patients with psychotropic drugs may further impair sexual function by adverse effects on libido, erection, ejaculation, and orgasmic function.
Selective serotonin-reuptake inhibitors (SSRIs) also have been reported to decrease libido in up to 40% of patients. SSRIs and tricyclic antidepressants (TCAs) have been shown to impair orgasmic function; indeed, they are used in clinical practice to treat premature ejaculation. The TCA amitriptyline has also been shown to decrease nocturnal penile tumescence; however, this effect has not been demonstrated with other TCAs. Drug-induced sexual dysfunction can be treated with careful selection of “sex-friendly” drugs, careful dose adjustment, and drug holidays.
Altered Genitourinary Tract Structure and Function
Cancers involving the genitourinary tract and their treatment may lead to structural and functional alterations and consequently have an impact on sexual function and pleasure associated with sexual activity. Anejaculation following retroperitoneal lymph node dissection (RPLND) for testicular cancer is a major concern for young patients who desire paternity after successful cancer treatment. All patients experience anejaculation following radical prostatectomy, and up to 74% describe orgasmic dysfunction manifested as decreased or absent orgasm.[12,13] Involuntary loss of urine has also been described by patients after radical prostatectomy and occurs in 93% of patients within the first year after radical prostatectomy.
Patients with urologic cancer may suffer penile deformities as a consequence of penile skin or distal urethral tumors and their treatment- either surgery (penectomy, urethrectomy) or local irradiation, which may cause penile fibrosis and resultant deformity. However, penile deformities occur not only as a consequence of treatment for penile cancer: Radiotherapy for other pelvic tumors that includes the genitalia may cause local penile or genital skin reactions, temporarily precluding sexual activity or permanent changes in penile sensation.
Moreover, penile structural changes have been described after surgical treatment of prostate cancer. In a prospective study, Savoie et al recently confirmed previously reported data describing penile shortening of 0.5 to 5 cm in two-thirds of patients undergoing radical prostatectomy. However, to what extent these anatomic changes (without accompanying ED) affect sexual function is not clear.[15,16] The impact of other extensive pelvic operations or of pelvic irradiation on penile length has not been described thus far. However, it cannot be presumed to be nonexistent in light of the vascular insults and resultant fibrosis following application of these treatment modalities.
Hypogonadism in cancer patients undergoing treatment and cancer survivors is a well-recognized cause of decreased libido, ED, and sexual dysfunction. Hypogonadism may be encountered among prostate cancer patients receiving androgen deprivation therapy adjuvant to definitive radiotherapy or for recurrent disease after failed definitive treatment.[17,18] Bilateral orchiectomy for bilateral testicular tumors leads ultimately to severe hypogonadism and requires hormonal replacement therapy. Although bilaterality of testis cancer is relatively rare and occurs in only 1% of testis cancer patients, the risk of hypogonadism is markedly increased among survivors of testicular cancer even after unilateral orchiectomy, and even without chemotherapy.[19,20] This risk is further increased with increased treatment intensity.
Hypogonadism and Leydig cell dysfunction, transient or permanent, has also been described in patients with hematologic malignancies undergoing intensive chemotherapy and bone marrow transplantation, with or without whole-body irradiation.[21,22] Sexual dysfunction and ED in these patients may also involve psychological, vascular, or other factors. Treatment-related hypogonadism may also be caused by chronic opioid use and radiotherapy to the base of the skull.[10,23] Primary testicular failure (primary hypogonadism) and depression of gonadotrophin secretion axis (secondary hypogonadism) have also been described in chronic and acute illnesses, including cancer. The exact underlying pathophysiologic mechanism of this endocrine insufficiency is poorly understood. However, hypogonadism may worsen with weight loss and disease progression.
Neurogenic Sexual Dysfunction
Normal sexual function requires intact neurologic pathways. Neural pathways involved in sexual function originate in S2-S4 nerve roots and include the superior hypogastric plexus, inferior hypogastric plexus, pudendal nerve, cavernosal nerve, and pelvic splanchnic nerves. Although the most commonly studied form of neurogenic sexual dysfunction in cancer patients is ED following insult to the neurovascular bundles that travel along the dorsolateral aspect of the prostate in radical prostatectomy or radical cystectomy, erectile function is not the sole component of surgical treatment-related neurogenic sexual dysfunction. Normal sexual function incorporates sensory, motor (eg, pudendal nerve to bulbospongiosus and ischiocavernosus muscles), sympathetic, and parasympathetic activities to achieve erection, ejaculation, and orgasm.
While neural structures involved in the conduction of sympathetic activity may be disrupted during RPLND for testicular cancer, resulting in impaired ejaculation, erection is usually preserved. Extensive pelvic surgery for rectal cancer may damage all the previously described neural structures, leading to impairment of ejaculation, erection, and orgasm. With advances in surgical techniques and the advent of nerve-sparing surgery for prostate cancer, bladder cancer, and testicular cancer, surgery-induced neural damage and resultant neurogenic sexual dysfunction can be minimized.
Vasculogenic Sexual Dysfunction
Cancer treatment-related vascular damage impairs erectile function, while other domains of sexual health are not known to be affected. Upon sexual stimulation, an adequate arterial blood inflow and a competent veno-occlusive mechanism are required to achieve functional erection, both of which may be adversely affected by cancer-related treatment.
Vasculogenic ED notoriously occurs following pelvic radiotherapy. Radiation has been shown to induce endothelial proliferation, fibroblast proliferation, collagen deposition, and microvascular fibrosis accelerating existing arteriosclerosis and atherosclerosis, leading to occlusive vascular disease.[26,27] Pelvic arteriography after pelvic radiotherapy demonstrates bilateral narrowing of the internal iliac arteries and tortuosity and occlusions of the internal pudendal and penile arteries. Following radiotherapy, months to years may elapse before clinical ED is evident.
Vasculogenic ED-in particular, venous leak (deficient penile valve function)-has been reported to occur not only following radiotherapy, but also as a consequence of cavernous nerve injury during pelvic surgery. This results in corporal fibrosis, erectile tissue apoptosis, and disruption of the penile venoocclusive mechanism.[29,30]
The author(s) have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
1. Jemal A, Murray T, Ward E, et al: Cancer statistics, 2005. CA Cancer J Clin 55:10-30, 2005.
2. Incrocci L, Madalinska JB, Essink-Bot ML, et al: Sexual functioning in patients with localized prostate cancer awaiting treatment. J Sex Marital Ther 27:353-363, 2001.
3. Litwin MS, Lubeck DP, Henning JM, et al: Differences in urologist and patient assessments of health related quality of life in men with prostate cancer: Results of the CaPSURE database. J Urol 159:1988-1992, 1998.
4. Ananth H, Jones L, King M, et al: The impact of cancer on sexual function: A controlled study. Palliat Med 17:202-205, 2003.
5. McKinlay JB, Digruttolo L, Glasser D, et al: International differences in the epidemiology of male erectile dysfunction. Int J Clin Pract Suppl 102:35, 1999.
6. Schover LR: Counseling cancer patients about changes in sexual function. Oncology (Williston Park, NY) 13:1585-1596 (incl discussion), 1999.
7. Costabile RA: Cancer and male sexual dysfunction. Oncology (Williston Park, NY) 14:195-205 (incl discussion), 2000.
8. Lidstone V, Butters E, Seed PT, et al: Symptoms and concerns amongst cancer outpatients: Identifying the need for specialist palliative care. Palliat Med 17:588-595, 2003.
9. Rajagopal A, Vassilopoulou-Sellin R, Palmer JL, et al: Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids. Cancer 100:851-858, 2004.
10. Daniell HW: Hypogonadism in men consuming sustained-action oral opioids. J Pain 3:377-384, 2002.
11. Clayton DO, Shen WW: Psychotropic drug-induced sexual function disorders: Diagnosis, incidence and management. Drug Saf 19:299-312, 1998.
12. Koeman M, van Driel MF, Schultz WC, et al: Orgasm after radical prostatectomy. Br J Urol 77:861-864, 1996.
13. Barnas JL, Pierpaoli S, Ladd P, et al: The prevalence and nature of orgasmic dysfunction after radical prostatectomy. BJU Int 94:603-605, 2004.
14. Chen CT, Valicenti RK, Lu J, et al: Does hormonal therapy influence sexual function in men receiving 3D conformal radiation therapy for prostate cancer? Int J Radiat Oncol Biol Phys 50:591-595, 2001.
15. Munding MD, Wessells HB, Dalkin BL: Pilot study of changes in stretched penile length 3 months after radical retropubic prostatectomy. Urology 58:567-569, 2001.
16. Savoie M, Kim SS, Soloway MS: A prospective study measuring penile length in men treated with radical prostatectomy for prostate cancer. J Urol 169:1462-1464, 2003.
17. Higano CS: Side effects of androgen deprivation therapy: Monitoring and minimizing toxicity. Urology 61:32-38, 2003.
18. Hollenbeck BK, Wei JT, Sanda MG, et al: Neoadjuvant hormonal therapy impairs sexual outcome among younger men who undergo external beam radiotherapy for localized prostate cancer. Urology 63:946-950, 2004.
19. Che M, Tamboli P, Ro JY, et al: Bilateral testicular germ cell tumors: Twenty-year experience at M. D. Anderson Cancer Center. Cancer 95:1228-1233, 2002.
20. Nord C, Bjoro T, Ellingsen D, et al: Gonadal hormones in long-term survivors 10 years after treatment for unilateral testicular cancer. Eur Urol 44:322-328, 2003.
21. Chatterjee R, Kottaridis PD, McGarrigle HH, et al: Management of erectile dysfunction by combination therapy with testosterone and sildenafil in recipients of high-dose therapy for haematological malignancies. Bone Marrow Transplant 29:607-610, 2002.
22. Mertens AC, Ramsay NK, Kouris S, et al: Patterns of gonadal dysfunction following bone marrow transplantation. Bone Marrow Transplant 22:345-350, 1998.
23. Pai HH, Thornton A, Katznelson L, et al: Hypothalamic/pituitary function following high-dose conformal radiotherapy to the base of skull: Demonstration of a dose-effect relationship using dose-volume histogram analysis. Int J Radiat Oncol Biol Phys 49:1079-1092, 2001.
24. Baker HW: Reproductive effects of nontesticular illness. Endocrinol Metab Clin North Am 27:831-850, 1998.
25. Banerjee AK: Sexual dysfunction after surgery for rectal cancer. Lancet 353:1900-1902, 1999.
26. Mirone V, Imbimbo C, Palmieri A, et al: Erectile dysfunction after surgical treatment. Int J Androl 26:137-140, 2003.
27. Basavaraju SR, Easterly CE: Pathophysiological effects of radiation on atherosclerosis development and progression, and the incidence of cardiovascular complications. Med Phys 29:2391-2403, 2002.
28. Incrocci L, Slob AK, Levendag PC: Sexual (dys)function after radiotherapy for prostate cancer: A review. Int J Radiat Oncol Biol Phys 52:681-693, 2002.
29. De Luca V, Pescatori ES, Taher B, et al: Damage to the erectile function following radical pelvic surgery: Prevalence of veno-occlusive dysfunction. Eur Urol 29:36-40, 1996.
30. Montorsi F, Briganti A, Salonia A, et al: Current and future strategies for preventing and managing erectile dysfunction following radical prostatectomy. Eur Urol 45:123-133, 2004.
31. Surveillance, Epidemiology, and End
Results (SEER) Program (www.seer.cancer.gov), DevCan database: SEER Incidence and Mortality, 1993-2001. National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2004.
32. Wei JT, Dunn RL, Sandler HM, et al: Comprehensive comparison of health-related quality of life after contemporary therapies for localized prostate cancer. J Clin Oncol 20:557-566, 2002.
33. Stanford JL, Feng Z, Hamilton AS, et al: Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: The Prostate Cancer Outcomes Study. JAMA 283:354-360, 2000.
34. Merrick GS, Wallner KE, Butler WM: Management of sexual dysfunction after prostate brachytherapy. Oncology (Williston Park, NY) 17:52-73 (incl discussion), 2003.
35. Clark JA, Inui TS, Silliman RA, et al: Patients’ perceptions of quality of life after treatment for early prostate cancer. J Clin Oncol 21:3777-3784, 2003.
36. Brucker PS, Cella D: Measuring self-reported sexual function in men with prostate cancer. Urology 62:596-606, 2003.
37. Litwin MS, Flanders SC, Pasta DJ, et al: Sexual function and bother after radical prostatectomy or radiation for prostate cancer: Multivariate quality-of-life analysis from CaPSURE. Cancer of the Prostate Strategic Urologic Research Endeavor. Urology 54:503-508, 1999.
38. Talcott JA, Manola J, Clark JA, et al: Time course and predictors of symptoms after primary prostate cancer therapy. J Clin Oncol 21:3979-3986, 2003.
39. Potosky AL, Davis WW, Hoffman RM, et al: Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: The prostate cancer outcomes study. J Natl Cancer Inst 96:1358-1367, 2004.
40. Penson DF, Feng Z, Kuniyuki A, et al: General quality of life 2 years following treatment for prostate cancer: What influences outcomes? Results from the prostate cancer outcomes study. J Clin Oncol 21:1147-1154, 2003.
41. Rabbani F, Stapleton AM, Kattan MW, et al: Factors predicting recovery of erections after radical prostatectomy. J Urol 164:1929-1934, 2000.
42. Robinson JW, Moritz S, Fung T: Meta-analysis of rates of erectile function after treatment of localized prostate carcinoma. Int J Radiat Oncol Biol Phys 54:1063-1068, 2002.
43. Walsh PC: Radical prostatectomy for localized prostate cancer provides durable cancer control with excellent quality of life: A structured debate. J Urol 163:1802-1807, 2000.
44. Kundu SD, Roehl KA, Eggener SE, et al: Potency, continence and complications in 3,477 consecutive radical retropubic prostatectomies. J Urol 172:2227-2231, 2004.
45. Rassweiler J, Schulze M, Teber D, et al: Laparoscopic radical prostatectomy: Functional and oncological outcomes. Curr Opin Urol 14:75-82, 2004.
46. Lowentritt BH, Scardino PT, Miles BJ, et al: Sildenafil citrate after radical retropubic prostatectomy. J Urol 162:1614-1617, 1999.
47. Zelefsky MJ, McKee AB, Lee H, et al: Efficacy of oral sildenafil in patients with erectile dysfunction after radiotherapy for carcinoma of the prostate. Urology 53:775-778, 1999.
48. Merrick GS, Butler WM, Lief JH, et al: Efficacy of sildenafil citrate in prostate brachytherapy patients with erectile dysfunction. Urology 53:1112-1116, 1999.
49. Schoenberg MP, Walsh PC, Breazeale DR, et al: Local recurrence and survival following nerve sparing radical cystoprostatectomy for bladder cancer: 10-year followup. J Urol 155:490-494, 1996.
50. Brendler CB, Steinberg GD, Marshall FF, et al: Local recurrence and survival following nerve-sparing radical cystoprostatectomy. J Urol 144:1137-1141 (incl discussion), 1990.
51. Ries LAG, Eisner MP, Kosary CL et al: SEER Cancer Statistics Review, 1975-2001. Bethesda, Md; National Cancer Institute; 2004.
52. Jonker-Pool G, Van de Wiel HB, Hoekstra HJ, et al: Sexual functioning after treatment for testicular cancer-review and meta-analysis of 36 empirical studies between 1975-2000. Arch Sex Behav 30:55-74, 2001.
53. Baniel J, Foster RS, Rowland RG, et al: Complications of primary retroperitoneal lymph node dissection. J Urol 152:424-427, 1994.
54. Heidenreich A, Albers P, Hartmann M, et al: Complications of primary nerve sparing retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell tumors of the testis: experience of the German Testicular Cancer Study Group. J Urol 169:1710-1714, 2003.
55. Jacobsen KD, Ous S, Waehre H, et al: Ejaculation in testicular cancer patients after post-chemotherapy retroperitoneal lymph node dissection. Br J Cancer 80:249-255, 1999.
56. Windahl T, Andersson SO: Combined laser treatment for penile carcinoma: Results after long-term followup. J Urol 169:2118-2121, 2003.
57. Pietrzak P, Corbishley C, Watkin N: Organ-sparing surgery for invasive penile cancer: Early follow-up data. BJU Int 94:1253-1257, 2004.
58. D’Ancona CA, Botega NJ, De Moraes C, et al: Quality of life after partial penectomy for penile carcinoma. Urology 50:593-596, 1997.
59. Windahl T, Skeppner E, Andersson SO, et al: Sexual function and satisfaction in men after laser treatment for penile carcinoma. J Urol 172:648-651, 2004.