Treatment-Related Factors Secondary to Surgery
        Breast cancer
        Colorectal cancer
        Prostate 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

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]

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.

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] Adjuvant tamoxifen therapy increases the rate of hot flashes, night sweats, and vaginal discharge, and increases the risk of premature menopause 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.[9,10]

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 satisfication. As noted in other studies of women with breast cancer, sexual changes were more common among younger patients.[11]

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).[12,13] 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.[14]

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,[15] 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.[15] 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.[16] 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.[17] 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.[18]

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.[19] 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%.[20-24] Retrospective cohort studies have provided evidence indicating superior potency results with bilateral nerve-sparing surgical techniques.[25,26] 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.[27] 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.[28]

Other studies suggest that three-dimensional conformational radiation therapy may be superior to radical prostatectomy in preserving erectile function.[21,29-34] Rates of potency are typically in the 30% to 60% range, with conformal therapy superior to older techniques.[21,35-37] 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%).[38] 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.[39] Radiation therapy appears to damage the arterial system that transports blood to the penis.[40] 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.[41]

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).[42] With brachytherapy, ejaculation is preserved and age (91% of men younger than 50 years) correlates with return of sexual function.[43] However, a decline in potency as a function of time following treatment is expected in patients treated with brachytherapy.[42] 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 remaining so 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%.[42]

The etiology of erectile dysfunction following brachytherapy is unknown; however, radiation damage to nerve bundles and vascular structures has been proposed as a cause.[42] One study investigated retrospectively the relationships between the dose of radiation to structures putatively involved in prostate brachytherapy–induced 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]

Nerve-sparing approaches to surgery appear to enhance recovery of erections at least to some degree after radical cystectomy [47,48] and colorectal surgery.[49,48] 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;[50,51] 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.[52] 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.[53] 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.[54] Rather, it is the quality of a woman’s relationship with her partner that correlates with sexual function.[55] 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.[56]

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.[57] 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.[3,58-60] Premature ovarian failure secondary to chemotherapy or radiation brings the sudden onset of menopausal symptoms, and women who experience sudden loss of estrogen and androgen production 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.[61] 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.[62] Because of concerns over causing recurrence of breast cancer, hormone replacement therapy is often not recommended for women who have become menopausal during treatment.[63]

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.[64]

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.[65,66] Systemic chemotherapy in men occasionally interferes with testosterone production in the testicles.[67] 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.[68]

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.[69,70] 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.[71] Women who receive radiation should be educated regarding the use of vaginal dilators. Vascular compromise can be temporary or permanent.[72] For men with rectal cancer, pelvic radiation has been associated with difficulties attaining or maintaining erection.[73,74] The exact etiology of sexual dysfunction after radiation therapy remains unknown [14] but likely relates to arterial damage of the penile arteries, limiting blood flow needed for successful erection.[40] 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.[75]

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.[76-79] 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,[80] giving intermittent hormone therapy as needed to suppress PSA,[81] or using a combination of finasteride and an androgen-receptor blocker instead of hormone treatments that totally eliminate androgen production.[82] It is not yet clear, however, whether men who try these modified treatment regimens are compromising the length of their survival.

Tamoxifen for breast cancer, described as an antiestrogenic drug, actually acts like a weak estrogen in the genital tract.[83] 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.[84,10] 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.[63] Another study found that use of tamoxifen did not make a significant independent contribution to the prediction of impact on sexuality.[85] 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.[86] 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.

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.[87] 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;[88] 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.[89] 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.[90]

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.[91] 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.

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