NCI/PDQ^® Health professionals: Sexuality and Reproductive Issues (PDQ®)

National Cancer Institute
Ultima Vez Modificado: 14 de junio del 2012

TABLE OF CONTENTS

• The Prevalence and Types of Sexual Dysfunction in People With Cancer

• Factors Affecting Sexual Function in People With Cancer
  • Treatment-related Factors Secondary to Surgery
    • Breast cancer
    • Colorectal cancer
    • Prostate cancer
      • Orgasm alterations
        • Tamsulosin
        • Climacturia
      • Penile length alterations
        • Anatomical fibrotic changes
        • Physiological-functional alterations
    • Testicular cancer
    • Other pelvic tumors
  • Treatment-related Factors Secondary to Systemic Chemotherapy
  • Treatment-related Factors Secondary to Radiation
  • Treatment-related Factors Secondary to Hormone Therapy
  • Psychological Factors
  • Pediatric Cancer Survivors

• Assessment of Sexual Function in People With Cancer
  • General Factors Affecting Sexual Functioning Evaluated in Assessment
    • Current sexual status
    • Premorbid sexual functioning
  • Psychosocial Aspects of Sexuality
    • Relationship status
    • Psychological status
  • Medical Aspects of Sexuality

• Pharmacological Effects of Supportive Care Medications on Sexual Function
  • Effect of Opioids on Sexual Function
  • Selective Serotonin Reuptake Inhibitors

• Treatment of Sexual Problems in People With Cancer
  • Current Clinical Trials

• Fertility Issues
  • Chemotherapy
  • Radiation
  • Preventive Strategies
  • Procreative Alternatives
  • Current Clinical Trials

• Changes to This Summary (06/14/2012)

• Questions or Comments About This Summary

• About This PDQ® Summary
  • Purpose of This Summary
  • Reviewers and Updates
  • Levels of Evidence
  • Permission to Use This Summary
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The Prevalence and Types of Sexual Dysfunction in People With Cancer

Sexuality is a complex, multidimensional phenomenon that incorporates biologic, psychologic, interpersonal, and behavioral dimensions. It is important to recognize that a wide range of normal sexual functioning exists. Ultimately, sexuality is defined by each patient and his/her partner within a context of factors such as gender, age, personal attitudes, and religious and cultural values.

Many types of cancer and cancer therapies are frequently associated with sexual dysfunction. Across sites, estimates of sexual dysfunction after various cancer treatments have ranged from 40% to 100%. 1 Most of the information relates to women who have breast or gynecologic cancer and men who have prostate cancer. Less is known about how other types of cancersin particular, other solid tumorsaffect sexuality. Research suggests that about 50% of women who have had breast cancer experience long-term sexual dysfunction, 2 3 as do a similar proportion of women who have had gynecologic cancer. 4 For men with prostate cancer, erectile dysfunction (erections inadequate for intercourse) has been the primary form of sexual dysfunction investigated. Prevalence rates of erectile dysfunction have varied. In general, those studies that have used patients' self-reports have found higher rates of erectile dysfunction ranging from 60% to 90% after radical prostatectomy and between 67% and 85% following external-beam radiation therapy. 5 6 7 8 Erectile dysfunction appears to be least prevalent with brachytherapy and most prevalent when cryotherapy is used to treat localized prostate cancer. 9 For Hodgkin lymphoma and testicular cancer, 25% of people who have had these cancers are left with long-term sexual problems. 3 10

Several summary articles on sexuality and cancer give particular emphasis on cancer sites that have a direct impact on sexual functioning. 11 12 13 An individual's sexual response can be affected in a number of ways, and the causes of sexual dysfunction are often both physiological and psychological. The most common sexual problems for people with cancer are loss of desire for sexual activity in men and women, erectile dysfunction in men, and dyspareunia (pain with intercourse) in women. 3 Men may also experience anejaculation (absence of ejaculation), retrograde ejaculation (ejaculation going backward to the bladder), or the inability to reach orgasm. Women may experience changes in genital sensations due to pain or a loss of sensation and numbness, as well as a decreased ability to reach orgasm. Loss of sensation can be as distressing as painful sensation for some individuals. 14 In women, premature ovarian failure as a result of chemotherapy or pelvic radiation therapy is a frequent antecedent to sexual dysfunction, particularly when hormone replacement is contraindicated because the malignancy is hormonally sensitive. 2

Unlike many other physiological side effects of cancer treatment, sexual problems do not tend to resolve within the first year or two of disease-free survival; 2 7 15 16 17 18 19 rather, they may remain constant and fairly severe or even continue to increase. Although it is unclear how much sexual problems influence a survivor's rating of overall health-related quality of life, these problems are clearly bothersome to many patients and interfere with a return to normal posttreatment life. Assessment, referral, intervention, and follow-up are important for maximizing quality of life and survival. 2 17

In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.

In a qualitative study of 48 men (130 approached) with erectile dysfunction after treatment for early prostate cancer, 20 quality of life was significantly affected in areas such as the following:

• The quality of sexual intimacy.
• Everyday interactions with women.
• Sexual fantasy life.
• Perceptions of their masculinity.

Patients who participated in a randomized trial that compared radical prostatectomy with watchful waiting were asked to complete a questionnaire regarding symptoms, psychological functioning, and quality of life. 21 Although the frequency of sexual thoughts was similar in both groups, the prevalence of erectile dysfunction (changes in voluntary erection in sexual situations, erection on awakening, and spontaneous erections) was higher in the radical prostatectomy group (80%) than in the watchful-waiting group (45%). Among men who underwent radical prostatectomy, 56% were moderately or greatly distressed by the decline in sexual function, as compared with 40% of men in the watchful-waiting group. 21

In a different populationthat of male lymphoma survivorsa cross-sectional study of 15-year survivors of both Hodgkin and non-Hodgkin lymphoma compared sexual function and hormone levels with those of age-matched controls. 22 Overall, the authors concluded that sexual function (as measured by the Brief Sexual Function Inventory [BSFI]) was significantly worse in the lymphoma survivors than in controls. In univariate analysis, lower functioning was attributed to the following:

• Increased age.
• Lower testosterone.
• Higher luteinizing hormone.
• Greater fatigue and emotional distress.
• At least one comorbidity.

There are several cautions in interpreting these results:

• The types of comorbidities are not listed; hence, it is not known whether cardiovascular disease was prevalent.
• Multivariate analyses to look at the relative impact of the various contributing factors to lower functioning were not performed.
• Considering the overall mean scores, the BSFI subscale scores were neither that low nor that different from the scores of controls (a difference of <0.5) even though they were statistically significantly different, likely because of the large sample size.

Although the authors concluded that sexual function was worse, it was only slightly worse; however, it reached statistical significance. Therefore, it is not clear from this study how much sexual functioning contributed to distress or decreased quality of life. 22

References:

1. Derogatis LR, Kourlesis SM: An approach to evaluation of sexual problems in the cancer patient. CA Cancer J Clin 31 (1): 46-50, 1981 Jan-Feb. [PUBMED Abstract]
2. Ganz PA, Rowland JH, Desmond K, et al.: Life after breast cancer: understanding women's health-related quality of life and sexual functioning. J Clin Oncol 16 (2): 501-14, 1998. [PUBMED Abstract]
3. Schover LR, Montague DK, Lakin MM: Sexual problems. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1997, pp 2857-2872. [PUBMED Abstract]
4. Andersen BL: Quality of life for women with gynecologic cancer. Curr Opin Obstet Gynecol 7 (1): 69-76, 1995. [PUBMED Abstract]
5. Walsh PC, Epstein JI, Lowe FC: Potency following radical prostatectomy with wide unilateral excision of the neurovascular bundle. J Urol 138 (4): 823-7, 1987. [PUBMED Abstract]
6. Talcott JA, Rieker P, Clark JA, et al.: Patient-reported symptoms after primary therapy for early prostate cancer: results of a prospective cohort study. J Clin Oncol 16 (1): 275-83, 1998. [PUBMED Abstract]
7. Smith DS, Carvalhal GF, Schneider K, et al.: Quality-of-life outcomes for men with prostate carcinoma detected by screening. Cancer 88 (6): 1454-63, 2000. [PUBMED Abstract]
8. 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 (3): 354-60, 2000. [PUBMED Abstract]
9. 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 (4): 1063-8, 2002. [PUBMED Abstract]
10. Arai Y, Kawakita M, Okada Y, et al.: Sexuality and fertility in long-term survivors of testicular cancer. J Clin Oncol 15 (4): 1444-8, 1997. [PUBMED Abstract]
11. Roth AJ, Carter J, Nelson CJ: Sexuality after cancer. In: Holland JC, Breitbart WS, Jacobsen PB, et al., eds.: Psycho-oncology. 2nd ed. New York, NY: Oxford University Press, Inc., 2010, pp 245-50. [PUBMED Abstract]
12. Lamb MA: Sexuality and Sexual Functioning. In: McCorkle R, Grant M, Frank-Stromborg M, et al., eds.: Cancer Nursing: A Comprehensive Textbook. 2nd ed. Philadelphia, Pa: WB Saunders Co, 1996, pp 1105-1127. [PUBMED Abstract]
13. Ofman US, Auchincloss SS: Sexual dysfunction in cancer patients. Curr Opin Oncol 4 (4): 605-13, 1992. [PUBMED Abstract]
14. Havenga K, Maas CP, DeRuiter MC, et al.: Avoiding long-term disturbance to bladder and sexual function in pelvic surgery, particularly with rectal cancer. Semin Surg Oncol 18 (3): 235-43, 2000 Apr-May. [PUBMED Abstract]
15. Fossí SD, Woehre H, Kurth KH, et al.: Influence of urological morbidity on quality of life in patients with prostate cancer. Eur Urol 31 (Suppl 3): 3-8, 1997. [PUBMED Abstract]
16. Helgason AR, Adolfsson J, Dickman P, et al.: Factors associated with waning sexual function among elderly men and prostate cancer patients. J Urol 158 (1): 155-9, 1997. [PUBMED Abstract]
17. Litwin MS, Hays RD, Fink A, et al.: Quality-of-life outcomes in men treated for localized prostate cancer. JAMA 273 (2): 129-35, 1995. [PUBMED Abstract]
18. Relander T, Cavallin-Stíhl E, Garwicz S, et al.: Gonadal and sexual function in men treated for childhood cancer. Med Pediatr Oncol 35 (1): 52-63, 2000. [PUBMED Abstract]
19. Broeckel JA, Thors CL, Jacobsen PB, et al.: Sexual functioning in long-term breast cancer survivors treated with adjuvant chemotherapy. Breast Cancer Res Treat 75 (3): 241-8, 2002. [PUBMED Abstract]
20. Bokhour BG, Clark JA, Inui TS, et al.: Sexuality after treatment for early prostate cancer: exploring the meanings of "erectile dysfunction". J Gen Intern Med 16 (10): 649-55, 2001. [PUBMED Abstract]
21. Steineck G, Helgesen F, Adolfsson J, et al.: Quality of life after radical prostatectomy or watchful waiting. N Engl J Med 347 (11): 790-6, 2002. [PUBMED Abstract]
22. Kiserud CE, Schover LR, Dahl AA, et al.: Do male lymphoma survivors have impaired sexual function? J Clin Oncol 27 (35): 6019-26, 2009. [PUBMED Abstract]

Factors Affecting Sexual Function in People With Cancer

Sexual dysfunction may be multifactorial; both physical and psychological factors contribute to its development. Physical factors include functional damage secondary to cancer therapies, fatigue, and pain. In addition, cancer therapy such as surgery, chemotherapy, radiation therapy, and bone marrow transplantation may have a direct physiologic impact on sexual function. 1 Medications used to treat pain, depression, and other symptoms may contribute to sexual dysfunction. Psychological factors include misbeliefs about the origin of the cancer, guilt related to these misbeliefs, coexisting depression, changes in body image after surgery, and stresses to personal relationships that occur secondary to cancer. 2 3 Increasing age is often believed to be associated with decreased sexual desire and performance; however, in one study, elderly men reported that sex remains important to their quality of life, that performance can be maintained into the 70s and 80s, and that altered sexual function is distressing. 4

Treatment-related Factors Secondary to Surgery

A number of cancer treatments have a direct physiologic impact on sexual function. As treatment success has improved for some sites, attempts have been made to modify treatment to reduce sexual morbidity. Several predictors of postoperative sexual functioning include patient's age, premorbid sexual and bladder functioning, tumor location, tumor size, and extent of surgical resection.

Breast cancer

Sexual function after localized treatment for breast cancer has been the subject of a good deal of research. Several reviews concur that breast conservation or reconstruction have only a minor impact in preserving sexual function compared with a mastectomy alone. 5 6 Women who have breast conservation, in particular, are more likely to continue to enjoy breast caressing, but groups typically do not differ on less subtle variables such as the frequency of sex, ease of reaching orgasm, or overall sexual satisfaction. A cross-sectional survey of younger women (aged 50 years or younger) with breast cancer found in multivariate analyses that having a mastectomy was associated with greater problems in interest in sex; chemotherapy was associated with greater sexual dysfunction. 7 Other studies confirm that sexual quality of life is disrupted more among those receiving chemotherapy, those who have undergone total mastectomies, those whose cancers were detected at later stages, and those with more depressive symptoms near the time of diagnosis. 8 A large survey of women with breast cancer who were being treated with either adjuvant tamoxifen or adjuvant exemestane (an aromatase inhibitor) was conducted to evaluate the differences in menopausal symptoms associated with these two agents. After 1 year of use, exemestane was associated with fewer hot flashes and less vaginal discharge than tamoxifen but with more vaginal dryness, bone pain, and sleep disorders. 9

Few studies evaluate sexuality in women with breast cancer that recurs. One longitudinal study compared women who were recently diagnosed with recurrent cancer with matched patients who were disease free. The recurrence group had less frequent intercourse, although there were no differences in sexual or relationship satisfaction. As noted in other studies of women with breast cancer, sexual changes were more common among younger patients. 10

Colorectal cancer

Changes related to sexual functioning in men and women with colorectal cancer have not been well studied, and there is scant literature to illuminate the issues and provide understanding and effective solutions. There are, however, potential changes in sexual function that can result from commonly performed surgery, particularly surgery performed on people with rectal cancer. This section will describe the possible effects on male sexual function that can occur after rectal cancer surgery.

Sexual and urinary dysfunctions are recognized complications of resection for rectal cancer. The main cause of sexual dysfunction from surgical resection appears to be injury to the autonomic nerves in the pelvis along the distal aorta from blunt pelvic resection or undefined cutting. Incidence of genitourinary dysfunction depends on the type of surgery performed (i.e., the plane of dissection, the degree of preservation of the autonomic nerves, and the extent of pelvic dissection). 11 12 Nerve injury can occur via direct injury, by vascular damage to the vasa nervosa, or where the blood supply to the nerves that enter laterally is disrupted with traction or devascularization. 13

The neuroanatomy for sexual functioning requires an intact autonomic nervous system, which includes an interaction between the parasympathetic and sympathetic nervous systems. Erection (parasympathetic-mediated response) is governed by impulses traveling along the nervi erigentes that arise from the second, third, and fourth sacral nerves, 14 whereas ejaculation depends on sympathetic control. The sympathetic fibers originate from the lower thoracic and upper lumbar segments of the spinal cord. These fibers descend along the aorta, forming the superior hypogastric plexus near the aortic bifurcation. The plexus divides into two trunks, which enter the pelvis along its lateral walls as the hypogastric nerves. The parasympathetic fibers to the pelvis join the hypogastric nerves on each pelvic wall to form the pelvic plexuses. 14 One study provided a more extensive review of the anatomy of the pelvic autonomic nerves and the relation of these nerves to the mesorectal fascial planes. 15 Damage to the hypogastric (sympathetic) nerves or sacral splanchnic (parasympathetic) nerves, or both, during surgical resection are the most likely cause of urinary and sexual dysfunction. 16 Pelvic plexus preservation is necessary to maintain erectile functioning, and both hypogastric nerve and pelvic plexus preservation are necessary to maintain ejaculate function and orgasm. 17

Prostate cancer

In men, there is controversy whether the newer nerve-sparing technique for radical prostatectomy is more or less successful in preserving erectile function than definitive radiation therapy for localized prostate cancer. A 1994 survey of practice patterns found that 95% of randomly-sampled urologists considered surgery the treatment of choice for clinically localized prostate cancer in men younger than 70 years. 18 As follow-up studies of large groups of men undergoing radical prostatectomy have accumulated, estimates of the number who recover functional erections (firm enough to allow penile-vaginal penetration on most occasions) range from 10% to 40%, with estimates of functional erections following external-beam radiation therapy ranging from 15% to 33%. 19 20 21 22 23 Retrospective cohort studies have provided evidence indicating superior potency results with bilateral nerve-sparing surgical techniques. 24 25 One research group suggested that much of the superiority of nerve-sparing over standard surgical technique in preserving potency is an artifact of selection bias. 26 The men selected to receive nerve-sparing surgery are those with the best potential to recover adequate erections. A systematic literature review using MEDLINE and CANCERLIT from January 1997 to June 2003 concluded that patient selection and surgical technique are the major determinants of postoperative erectile function in patients receiving treatment for localized prostate cancer. For properly selected patients undergoing a nerve-sparing radical prostatectomy by an experienced surgeon, unassisted or medically assisted erections postoperatively should be achieved. 27

Other studies suggest that three-dimensional conformational radiation therapy may be superior to radical prostatectomy in preserving erectile function. 20 28 29 30 31 32 33 Rates of potency are typically in the 30% to 60% range, with conformal therapy superior to older techniques. 20 34 35 36 Men who are older and in poor health, however, are often directed into radiation therapy, so that researchers often report posttreatment sexual function only for the subgroup that began with good erections. Furthermore, long-term follow-up is needed in comparing surgery with radiation therapy because recovery of erectile function typically occurs within a year or so after radical prostatectomy, whereas the damaging impact of radiation on erectile function is slow and gradual, with declines still being observed as long as 2 or 3 years after treatment. A retrospective cohort study of men treated with either radical prostatectomy or external-beam radiation therapy (EBRT) revealed significantly greater prevalence of erectile dysfunction in the surgery group at 5 years after diagnosis (79.3% vs. 63.5%). 37 The mechanism of injury to erectile function also differs between surgery and radiation therapy. Radical prostatectomy damages nerves that direct blood flow into the penis, ultimately decreasing oxygenation of these tissues and increasing collagen deposits that interfere with the penile tissue relaxation essential for firm erection. 38 Radiation therapy appears to damage the arterial system that transports blood to the penis. 39 A retrospective review of population-based data suggests that the choice of primary treatment for prostate cancer is not associated with 2-year general health-related quality-of-life outcomes. 40

Prostate brachytherapy with permanent radioactive implants is an increasingly popular choice for the treatment of prostate cancer. Two isotopes are commonly used: iodine 125 (¹²⁵I) and palladium 103 (¹⁰³Pd). 41 With brachytherapy, ejaculation is preserved and age (91% of men younger than 50 years) correlates with return of sexual function. 42 However, a decline in potency as a function of time following treatment is expected in patients treated with brachytherapy. 41 43 One study found an actuarial preservation of potency after brachytherapy alone of 79% at 3 years and 59% at 6 years. 44 Another study found lower rates, with 57% of men fully potent or with mild erectile dysfunction at baseline and at 30 months postbrachytherapy. 45 Potency rates after brachytherapy are significantly influenced by the addition of EBRT and/or neoadjuvant hormonal deprivation. Patients who received brachytherapy alone had a 5-year potency rate of 76%, compared with a potency rate of 56% for those treated with brachytherapy and EBRT. Patients who received a combination of EBRT, neoadjuvant hormonal deprivation, and brachytherapy had a 5-year potency rate of 29%. 41

The etiology of erectile dysfunction following brachytherapy is unknown; however, radiation damage to nerve bundles and vascular structures has been proposed as a cause. 41 One study investigated retrospectively the relationships between the dose of radiation to structures putatively involved in prostate brachytherapyinduced erectile dysfunction and incidence of postbrachytherapy erectile dysfunction. This study found no increased risk of erectile dysfunction with increasing dose to the crus or neurovascular bundle, proposing a possible dose-response relationship between the risk of erectile dysfunction and radiation dose to the bulb. 46

Orgasm alterations

Despite advances in our understanding of the erectile mechanism, the orgasm process remains poorly understood. Although orgasm alterations receive little attention, they are not uncommon and can be categorized into three areas:

• Changes in orgasm.
• Orgasmic pain (dysorgasmia).
• Orgasm-associated incontinence.

A study of 1,236 men treated for localized prostate cancer (52% radical prostatectomy [RP], 48% radiation therapy) found that 65% of patients reported a problem with their orgasms, including 31% who no longer tried to reach orgasm, 17% who tried but were unable to reach orgasm, and 28% with orgasms that were disappointingly weak. 47

To define the type of orgasmic dysfunction in men after RP, one group of investigators used a survey, including questions addressing the following: 48

• Presence of orgasm.
• Absence of orgasm.
• Orgasm quality before surgery.
• Orgasm quality after surgery.
• Presence of orgasmic pain.
• Location of orgasmic pain.
• Consistency and duration of orgasmic pain.

Of the patients treated surgically:

• 22% reported no change in orgasm intensity.
• 37% reported a complete absence of orgasm.
• 37% had a decreased orgasm intensity.
• 4% reported a more intense orgasm after RP than before.

Pain during orgasm occurred in 14% of the patients, located in the penis (63%), abdomen (9%), rectum (24%), and other areas (4%). Most patients had orgasm-associated pain for less than a minute, one-third reported pain for 1 to 5 minutes, and 12% reported pain lasting more than 5 minutes. 48 No consensus on the etiology of orgasmic pain exists; however, it is thought that bladder neck/pelvic floor spasm plays a role.

Tamsulosin

A prospective, nonplacebo-controlled study was conducted to assess the use of tamsulosin, an alpha-adrenergic blocking agent, in patients with orgasmic pain. In this study, 77% of patients reported significant improvement in pain, and 12% noted complete resolution of their pain with significant increase in International Index of Erectile Function (IIEF) libido score, supporting the hypothesis that orgasmic pain is related to bladder neck and/or pelvic floor muscle spasm. 49

Climacturia

Urinary incontinence during orgasm (climacturia) is another phenomenon that may adversely affect satisfaction with sexual activity for men post-RP and for their partners. One group of investigators reported that climacturia occurred in 20% of patients after RP and that it was unrelated to the type of prostatectomy performed (open or laparoscopic). 50 Another group reported a higher prevalence of post-RP climacturia at 45%. 51 In 68% of the cases reported, climacturia occurred rarely or only occasionally, while in 21% of cases it occurred most of the time or always. Urine leakage amounted to only a few drops in 58% of patients, but 16% reported a loss of more than 1 oz. Bother was none or minimal in 52% of patients and significant in 48%.

There is no effective treatment to restore the nature of preoperative orgasm. Dysorgasmia can be managed symptomatically with alpha-blockers, and climacturia may be managed behaviorally (restricting fluid intake and emptying the bladder before sexual activity) or mechanically (using a rubber constriction ring or condoms, if the leakage amount is small).

Penile length alterations

One study has found a significant decrease in all penile dimensions after RP: decreased penile length of 8% and 9% and decreased volume of 19% to 22% in the flaccid and erect states, respectively. 52 The most substantial change occurred between the first 4 months and 8 months postsurgery. A measured decrement in penile length was found in 71% of men after RP, which was more than 1 cm in 48% of patients at 3 months postsurgery. 53 Similar findings were obtained in another study, with a decrease in the stretched penile length in 68% of patients and more than 15% decrease in 19% of patients. 54 Penile length shortening has been shown to be independently associated with nerve preservation status and with postoperative erectile function outcome.

Anatomical fibrotic changes

Anatomical fibrotic changes that showed significantly decreased elastic fibers and smooth muscle fiber content and increased collagen content have been demonstrated in comparisons of penile biopsies preoperatively and at 2 months and 12 months postoperatively. It is thought that the chronic absence of erectile activity leads to a state of cavernosal hypoxia, low oxygen tension, which favors the secretion of fibrogenic cytokines such as transforming growth factor-beta 1 (TGF-beta 1), while during erection the corporal smooth muscle is oxygenated. This results in the secretion of endogenous prostanoids (prostaglandin E1) which, in turn, inhibit fibrogenic cytokine production.

Physiological-functional alterations

In addition to anatomical changes, there are also physiological-functional alterations. It is well recognized that even in the hands of an experienced surgeon using nerve-sparing surgery, some degree of nerve injury is likely to occur to the cavernosal nerves. Sympathetic hyperinnervation (termed by some competitive sprouting) refers to the concept that when autonomic nerves are injured, sympathetic fibers are biologically primed to recuperate from injury and regenerate more quickly, resulting in unantagonized sympathetic tone in the end organ. After cavernosal nerve injury, this phenomenon results in a penile hypertonic state. Any factors that result in reduced nitric oxide secretion or increased sympathetic tone, such as nerve injury after RP, may lead to decreased relaxation or distensibility of corporal smooth muscle and may lead to shortening.

Regardless of the exact mechanism of penile length alteration, the common underlying mechanism of penile shortening and long-term erectile dysfunction may be structural changes that result from a combination of neural injuryassociated denervation resulting in smooth muscle degeneration and cavernosal hypoxia-induced collagen deposition.

Penile length changes can be divided into early and delayed:

• Early changes. Early changes occur in response to the neural injury during RP. The cavernosal nerves degenerate, and in the early phasewhen sympathetic nerve function is in the ascendancythe penis is contracted. Given that the penile smooth muscle is highly contractile in response to adrenergic tone, this results in a penis that patients often refer to as being drawn back in the body. This hypertonic state is most pronounced within the first 3 months to 6 months postsurgery. A clinical scenario supporting this is the circumcised man whose penis, soon after surgery, appears incompletely circumcised or even uncircumcised.
• Delayed structural changes. Delayed structural changes are more distressing to the patient, resulting from true irreversible structural alterations in the corporal smooth muscle. These structural changes most probably result from a combination of factors (as described above). The difference between these changes and early increased tone is shown by the reduced or absent penile stretch in the group with permanent smooth muscle alterations. It is easy to appreciate how these alterations affect not only length but also girth.

Testicular cancer

Men diagnosed with testicular cancer find changes in sexual function particularly worrisome. However, limited published data describing long-term sexual function in men postorchiectomy are encouraging. A Dutch study reported a decline in sexual function, including desire, during the first 3 months postsurgery, with function improving beyond baseline at 12 months. 55 In this study, being single was the main predictor of worse sexual functioning and/or less satisfaction with functioning at all time points. The type of treatment (orchiectomy alone vs. orchiectomy plus chemotherapy or radiation therapy) had no effect on sexual function. Depression was predictive at baseline and at 3 months but not at 12 months. 55

A French case-control study evaluated sexual outcomes in 106 men with testicular cancer who were 5 years postdiagnosis and disease free. 56 The control group was matched by age and geographic location. Both testicular cancer survivors and controls had equal rates of marriage, divorce, and separation. There was, however, a significant difference between survivors and controls with regard to sexual enjoyment, desire (P = .04), infertility (P < .001), and erectile dysfunction (P = .05). Loss of sexual activity and reduction of sexual intercourse did not differ between groups. 56

Similarly, a Norwegian study of more than 1,000 men with histories of testicular cancer (diagnosed and treated 418 years previously) found statistically significant differences on the Brief Male Sexual Function Inventory in the areas of erection, ejaculation, and desire in both younger men (aged 2039 years) and older men (aged 4059 years), compared to men of similar ages in the general population. 57 However, in contrast, the authors report that these statistically significant differences were small and not clinically meaningful. Men who received chemotherapy in addition to retroperitoneal lymph node dissection reported more trouble with ejaculation but no trouble in other sexual domains. As in the Dutch study described above, being single was the most important variable with respect to sexual problems. In addition, increasing age was associated with worse sexual scores in this study. 57

In summary, data suggest that although men with testicular cancer may report more problems with some aspects of sexual function, negative changes are mostly short term, with long-term function and activity being comparable to function and activity in the general population.

Other pelvic tumors

Nerve-sparing approaches to surgery appear to enhance recovery of erections at least to some degree after radical cystectomy 58 59 and colorectal surgery. 59 60 Although the sexual side effects of definitive radiation therapy for pelvic malignancies other than prostate cancer have not been well researched, outcomes similar to those after prostate cancer treatment would be expected when the dosage and field affect the pelvic vascular bed.

Pelvic surgeries in women include hysterectomy/oophorectomy, cystectomy, vulvectomy, and abdominoperineal resection and often involve removal of a portion of the vagina or other parts of the female genital anatomy. Older studies indicated that few women reported dyspareunia or loss of orgasmic capacity after radical hysterectomy; 61 62 however, a newer prospective study of women with early-stage cervical carcinoma who had undergone radical hysterectomy compared with control women reported severe orgasmic problems and uncomfortable sexual intercourse due to reduced vaginal size during the first 6 months after surgery. Throughout the first 2 years after surgery, the women reported persistent lack of sexual interest and lubrication. 63 Radical cystectomy for bladder cancer is more often associated with pain from reduced vaginal depth and caliber resulting from resection of the entire anterior vaginal wall. These patients may resume pain-free intercourse, normal sensation, and orgasm with the help of counseling, hormone therapy, and use of vaginal dilators. 64 Conservation of vaginal tissue may reduce some of these problems. Decreased morbidity has been reported from sparing of vulvar tissue with a partial vulvectomy versus radical vulvectomy, yet the amount of tissue resected has not been a good predictor of postoperative sexual satisfaction. 65 Rather, it is the quality of a woman's relationship with her partner that correlates with sexual function. 66 Women who undergo abdominoperineal resection may also report pain with intercourse related to loss of cushioning from removal of the posterior vaginal wall. In addition, pelvic adhesions or scarring may contribute to dyspareunia after an anterior/posterior resection. Radical resection of recurrent pelvic tumors in women (pelvic exenteration) involves partial or complete removal of the vagina and levator muscles. Vaginal reconstruction produces satisfactory function and aesthetic results in some patients. 67

Treatment-related Factors Secondary to Systemic Chemotherapy

Chemotherapy is associated with loss of desire and decreased frequency of intercourse for both men and women. Common side effects experienced after chemotherapy include nausea, vomiting, diarrhea, constipation, mucositis, weight changes (gain or loss), and altered sense of taste and smell. 3 These symptoms often leave individuals feeling asexual. Alopecia is often one of the most distressing side effects with associated changes in body image. 68 Loss of pubic hair can also be particularly uncomfortable, which, in turn, promotes asexual feelings.

For women, cytotoxic agents are associated with vaginal dryness, dyspareunia, reduced ability to reach orgasm, and for older women, greater risk of ovarian cancer. 3 69 70 71 Premature ovarian failure secondary to chemotherapy or radiation brings the sudden onset of menopausal symptoms, and women who experience sudden loss of estrogen from the ovaries experience a number of associated sexual changes. Sexual symptoms associated with estrogen deprivation include vaginal atrophy, thinning of the vulvar tissues and vagina, loss of tissue elasticity, decreased vaginal lubrication, hot flashes, increased frequency of urinary tract infections, mood swings, fatigue, and irritability. In addition, for younger women with breast cancer, menopausal symptoms as a result of therapy contribute to poorer health perception and quality of life. 72 A study of the psychosocial aspects of the transitional period between the end of primary breast cancer treatment and survivorship enrolled 558 women. They were treated with surgery (either mastectomy or lumpectomy) with and without chemotherapy, and the health outcomes examined included physical, emotional, and sexual functioning, as well as mood and symptoms. Sexual functioning was worse for women who received chemotherapy, regardless of the type of prior surgery (i.e., mastectomy or lumpectomy). These problems with sexual function were likely related to problems with vaginal lubrication and a change in menopausal status, both of which are more common in those receiving chemotherapy. 73 Because of concerns over causing recurrence of breast cancer, hormone replacement therapy is often not recommended for women who have become menopausal during treatment. 74

In women with malignancies of other types, however, estrogen replacement therapy can usually reverse many sexual problems. Providers should discuss with women the risks and benefits of hormone replacement therapy with consideration of each women's individual risk profile. The impact of menopause on sexual functioning and the arousal phase of the sexual response in particular are often not communicated to women who struggle to understand these changes in their sexual responsiveness. Women who have graft-versus-host disease (GVHD) after bone marrow transplantation may develop vaginal strictures and adhesions that interfere with intercourse. 75

For men, chemotherapy agents rarely play an obvious role in erectile dysfunction. 3 Some cytotoxic agents may cause nerve damage, but few reports indicate permanent loss of erections upon completion of treatment. Sexual dysfunction, including loss of desire and erectile dysfunction, is more common after bone marrow transplant, often associated with autonomic neuropathy or GVHD. 76 77 Systemic chemotherapy in men occasionally interferes with testosterone production in the testicles. 78 For those men who have damage to the testicles from chemotherapy, testosterone replacement may be necessary to restore sexual function. 3 More rarely, neurotoxic chemotherapies have been observed to interfere with ejaculation of semen at orgasm, presumably because of damage to autonomic nerves involved in the contractions of the prostate, seminal vesicles, and bladder neck. 79

Treatment-related Factors Secondary to Radiation

Like chemotherapy, radiation can produce side effects such as fatigue, nausea and vomiting, diarrhea, and other symptoms that can reduce feelings of sexuality. In particular, pelvic radiation often irritates the intestinal lining and may cause diarrhea. The fatigue and change in bowel habits associated with radiation likely contribute to loss of libido and decreased sexual activity reported for both men and women.

For women, pelvic radiation also causes changes in the vagina. Both external-beam radiation and implants damage the vaginal epithelium and basal layer of the mucosa, leading to vaginal stenosis and vascular fibrosis. These factors can then lead to long-term sexual dysfunction, painful pelvic examinations, dyspareunia, potential gonadal toxicity, infertility, and low-birth-weight pregnancy outcomes in survivorship. 80 81 A longitudinal prospective study of sexual function and vaginal changes after radiation therapy for cervical cancer found persistent sexual dysfunction and adverse vaginal changes throughout the 2 years after radiation therapy during which the women were followed; 85% had low or no sexual interest, 35% reported moderate to severe lack of lubrication, 55% had mild to severe dysfunction, and 30% were dissatisfied with their sexual life. 82 Women who receive radiation should be educated regarding the use of vaginal dilators. Vascular compromise can be temporary or permanent. 83 For men with rectal cancer, pelvic radiation has been associated with difficulties attaining or maintaining erection. 84 85 The exact etiology of sexual dysfunction after radiation therapy remains unknown 13 but likely relates to arterial damage of the penile arteries, limiting blood flow needed for successful erection. 39 Proposed etiologies include pudendal or sympathetic nerve injury, vascular occlusion of penile arteries, or decreased levels of testosterone. Often, sexual changes are insidious, with changes occurring from 6 months to 1 year after radiation as fibrosis develops. There is a greater risk of sexual morbidity in men who already have compromised quality of erections before cancer diagnosis. Other risk factors that contribute to greater risk of sexual morbidity include cigarette smoking, history of heart disease, hypertension, pretreatment potency, and/or diabetes. 86

Treatment-related Factors Secondary to Hormone Therapy

Hormone therapy for prostate cancer involves reducing circulating androgens as close to zero as possible. Because androgens also act in the brain to promote sexual desire, about 80% of men report a profound decrease in sexual interest, typically accompanied by erectile dysfunction and difficulty reaching orgasm. 87 88 89 90 Younger men, however, are sometimes able to continue adequate sexual function. With an increasing number of younger men diagnosed with asymptomatic but advanced prostate cancer found through prostate specific antigen (PSA) screening, more attention has been given to preventing some of the sexual morbidity of treatment. Some centers have experimented with delaying hormone therapy until the onset of symptoms, 91 giving intermittent hormone therapy as needed to suppress PSA, 92 or using a combination of finasteride and an androgen-receptor blocker instead of hormone treatments that totally eliminate androgen production. 93 It is not yet clear, however, whether men who try these modified treatment regimens are compromising the length of their survival.

Adjuvant tamoxifen therapy can increase the rate of hot flashes, night sweats, and vaginal discharge in women older than 45 years by approximately 10%. Furthermore, though rates of sexual activity with a partner did not decline, women taking tamoxifen reported slightly increased rates of difficulty with sexual arousal and achieving orgasm. 94 95Tamoxifen for breast cancer, described as an antiestrogenic drug, actually acts like a weak estrogen in the genital tract. 96 The medication has anecdotally been reported to be associated with vaginal dryness and excessive vaginal lubrication, soreness, as well as occasional decrease in sexual desire and orgasmic delay. 95 97 The results of the few studies to examine women's actual sexual function while taking tamoxifen are not conclusive or easily compared because each study utilized different measures and statistical analyses. One study found no difference in reported sexual problems among women taking tamoxifen and women who received no systemic therapy, when adjusted for age. 6 Another study similarly found no significant effect of tamoxifen on sexual functioning utilizing a different measure and examining the effect only in women aged 50 years and older. 74 Another study found that use of tamoxifen did not make a significant independent contribution to the prediction of impact on sexuality. 98 Results from a study with a limited sample size of women taking tamoxifen, however, noted a differential estrogen effect by age, such that an estrogen effect was seen on the vaginal smears of 34 of 49 participants and was more common in older patients (P = .054). The presence of an estrogen effect was correlated with negative reactions during sex (P = .02) and vaginal dryness or tightness (P = .046). This study raised the possibility that tamoxifen may have antagonist effects on the vagina of younger women and estrogen agonist effects on postmenopausal women. 99 Prospective study of sexual functioning with evaluation of physiologic status (e.g., vaginal mucosa and hormone levels) before and after introduction of systemic therapy continues to be warranted. The impact of tamoxifen on sexuality and mood is still not clearly understood.

Psychological Factors

Loss of interest in sex is likely to be secondary to psychological factors. It is not uncommon for both men and women to believe, though incorrectly, that past sexual activity, an extramarital affair, sexually transmitted disease, or abortion has caused their cancer. Some believe, again incorrectly, that sexual activity may promote a recurrence of their tumor. This misbelief is especially common in individuals with a malignancy of the pelvic or genital area. These individuals may need reassurance that cancer is not transmissible via sexual contact. Women with squamous cell carcinoma of the cervix have often read or been told that this cancer is associated with the sexually transmitted human papillomavirus. 100 Guilt about past sexual activity or concern about potential harm to a partner are issues that should be addressed in these patients. The health care provider can clarify that it is the virus and not the cancer that is transmissible through sexual contact.

Loss of sexual desire or a decrease in sexual pleasure is a common symptom of depression. Depression is 15% to 25% more prevalent in patients with cancer than in the healthy population; 101 therefore, an assessment to rule out depression is an important part of evaluating sexual dysfunction. Sometimes people present with complaints of sexual dysfunction, feeling less stigmatized having a physical medical problem than they do by acknowledging that they are depressed. Treating depression can be helpful in alleviating sexual dysfunction. Attention should be paid to the sexual side effects of antidepressants in clinical decision making. (Refer to the PDQ® summary on Depression for more information.)

Changes in body image may interfere with sexual desire in some cancer survivors, but the impact of disfiguring cancer treatments, such as mastectomy, has been exaggerated. For example, breast conservation may result in better self-rated physical attractiveness in women compared with mastectomy alone, but these groups of women do not differ in their sexual activity or satisfaction. On the other hand, weight gain after chemotherapy for breast cancer may be underestimated as a factor that decreases a woman's feelings of attractiveness. 102 Having an ostomy for elimination of stool or urine can also affect a man's or woman's sense of being sexually attractive. Specific coping strategies have been suggested to overcome these problems. 103

One study attempted to explore the relationships between several relevant factors that can affect sexual function in 175 women with gynecologic cancer. 104 These factors included the following:

• Body image.
• Mood.
• Vaginal changes.
• Fatigue.
• Partner sexual function.
• Physical symptoms.
• General demographics such as socioeconomic status.

After controlling for sociodemographic factors, the authors concluded that physical symptoms/health status, partner function, and sexual self-image (called sexual self-schema) contributed significantly to sexual behavior, responsiveness, and satisfaction. In fact, the authors found that sexual self-schema actually served as a buffer between lack of sexual satisfaction and moodthat is, women with a more positive sexual self-image had fewer depressed symptoms when their sexual satisfaction was poor. Therefore, interventions that target cognitive representations may improve certain outcomes related to sexual health and functioning. 104

The stress of cancer diagnosis and ongoing therapy can exacerbate underlying marital tensions. This can likewise affect the sexual relationship. Men or women who do not have a committed relationship also have to face the potential trauma of being rejected by a new partner who learns about his or her history of cancer. 3 Some avoid all dating relationships out of fear of such rejection. One premorbid personality factor that may play a role in whether a man or woman stays sexually active after cancer is the sexual self-schema (i.e., whether an individual regards his or her own sexuality in a positive light). Women with negative sexual self-schemas were less likely to resume sex or have good sexual function after treatment for gynecological cancer. 105 One of the most important factors in adjusting after cancer is the person's feelings about his or her sexuality before cancer. That does not mean, however, that this is not a good opportunity to help a person explore those issues.

Pediatric Cancer Survivors

A cross-sectional survey of 599 survivors of pediatric cancer from three U.S. institutions in Southern California and the Midwest was conducted. 106 Types of cancer included the following:

• Leukemia (38%).
• Hodgkin/non-Hodgkin lymphoma (25%).
• Central nervous system/brain tumor (13%).
• Solid and soft tissue tumors (12%).
• Wilms tumor (4%).

Respondents had to be 21 years of age or younger at diagnosis and had to be 18 to 39 years of age at the time of the study. The mean age at diagnosis for the sample was 11 years, and the mean number of years since diagnosis was 16. The mean age of the sample was 27 years. Overall, 52% of women and 32% of men reported some problems in sexual functioning, with 43% citing at least one specific symptom. Erections were reported as being somewhat or very much of a problem by 8.5% of men. Becoming sexually aroused was reported as being somewhat or very much of a problem by 17% of women and 7% of men, and a lack of interest was reported by 19% of women and 10% of men. Emotional and physical comorbidities were more strongly associated with problems in sexual functioning.

Predictors of sexual problems in women included being married and reporting health problems; in men, lower income and reporting health problems were significant predictors. 106 While more women reported problems with sexual symptoms, men reported more distress. Limitations of this study include that it was a cross-sectional survey subject to selection/response bias. Results of this study cannot directly link sexual sequelae to a cancer diagnosis or to cancer treatment. However, particularly for men, the extent of sexual dysfunction reported is not generally seen in a cohort this young.

References:

1. Watson M, Wheatley K, Harrison GA, et al.: Severe adverse impact on sexual functioning and fertility of bone marrow transplantation, either allogeneic or autologous, compared with consolidation chemotherapy alone: analysis of the MRC AML 10 trial. Cancer 86 (7): 1231-9, 1999. [PUBMED Abstract]
2. Schover LR, Montague DK, Lakin MM: Sexual problems. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1997, pp 2857-2872. [