Historical perspective

Sexual dysfunction has been recognized as a morbidity of cancer treatment since the 1950s. Early publications focused on mutilating surgery for breast cancer, impaired body image, and loss of feminine identity.¹ Research later revealed that systemic therapy plays a much greater role in sexual morbidity than local treatment of the breast.²

By the 1980s, radical pelvic surgery was redesigned to spare autonomic nerves responsible for penile blood flow.³ However, nerve-sparing radical prostatectomy resulted in a return to baseline erectile function in less than 25% of men.⁴ More recently, robotic-assisted laparoscopic prostatectomy (RALP) has claimed to increase the accuracy of nerve-sparing and enhance recovery of normal erections. Although RALP shortens hospital stays and decreases acute complications, two large studies using Medicare and Surveillance, Epidemiology, and End-Results (SEER) databases found no advantage over open surgery in preserving sexual function and a disadvantage in urinary incontinence.^{5, 6}

Attempts to minimize sexual consequences of pelvic radiotherapy began with the introducing brachytherapy⁷ or computerized three-dimensional conformal fields for external beam treatment.⁸ Long-term preservation of sexual function again proved disappointing, as did later efforts using intensity-modulated radiation therapy or proton beams.^{8, 9}

In the 1980s, sexual function began to be considered in women with gynecological malignancies.¹⁰ As in men, attempts were made to spare nerves and tissues contributing to sexual pleasure and function during surgery or adjuvant radiation therapy.⁹ However, premature ovarian failure and exacerbation of vulvovaginal atrophy by pelvic radiotherapy were increasingly recognized as risk factors for sexual dysfunction.¹¹ Techniques from cognitive behavioral sex therapy, a short-term, action-oriented type of psychological treatment¹² were used with male and female cancer patients, including efforts to enhance relationship satisfaction and sexual communication.¹³

Nevertheless, fewer than 20% of cancer patients/survivors currently seek help when they have a sexual problem.^{14, 15} Few cancer centers offer treatment for sexual problems and sexual dysfunction remains a long-term unmet need for cancer survivors.^{16, 17}

Incidence and epidemiology—local and worldwide

About 59% of an estimated 14 million male cancer survivors in the United States, and 66% of women were treated for pelvic or breast tumors¹⁸ with at least a 50% prevalence of long-term, severe sexual dysfunction.¹⁹ Sexual problems affect at least 25% of survivors of treatment for nonreproductive cancers, including hematologic malignancies²⁰ and cancers of childhood.^{21, 22}

Given comparable prevalence and types of cancer in Europe and other industrialized nations, the risk for sexual dysfunction is similar.²³ Little information is available on sexual consequences of cancer in countries with low medical resources, but cancers potentiated by the human immunodeficiency virus (HIV) and the human papillomavirus (HPV) such as cervical, vulvar, anal, and penile cancer are more common, with a high likelihood of sexual morbidities.²⁴ The diagnosis can lead to divorce and ostracism in rural areas where cancer is stigmatized.²⁵

Sexual problems related to cancer are severe and generalized, including loss of desire for sex or ability to get aroused and reach orgasm, and interference from fatigue, pain, or incontinence.¹⁹ Without professional treatment, most problems do not resolve with time. Most dysfunctions are caused by cancer treatment,¹⁹ including damage to autonomic nerves in the pelvis, reducing genital blood flow during sexual arousal,^{3, 4} especially for men,²⁶ and direct damage to genital blood vessels and tissue from pelvic radiation therapy.⁹ Male erectile dysfunction also results from decreased genital blood flow after surgical interruption of blood vessels²⁷ or radiation damage.⁹ Without regular inflow of oxygenated blood, erectile tissue in the penis atrophies. As a result, too much blood drains into the venous system, limiting erectile rigidity.²⁷

Although the vagina expands and the clitoris swells with sexual arousal in women,²⁸ damage to hemodynamics is poorly understood. It is clear that estrogen deprivation plays a major role in female sexual problems,^{19, 29, 30} decreasing the lubrication produced during sexual arousal by the vaginal mucosa. With vulvovaginal atrophy, sexual caressing and penetration become painful, often leading to loss of desire to engage in sex and difficulty reaching orgasm.³¹

In both men and women, loss of desire frequently ends with avoiding sexual encounters.¹⁹ Low androgen levels are sometimes a factor in loss of desire for men, for example, during anti-androgen therapy for prostate cancer,³² after intensive chemotherapy,³³ or after radiation that damages the testes.³⁴

Risk factors—premorbid sexual function, cancer treatments, and behavioral characteristics

Many people have sexual problems before their cancer diagnosis, especially men. Erectile dysfunction is strongly associated with age-related cardiovascular disease, hypertension, diabetes, smoking, sedentary lifestyle, and obesity.^{35, 36} Erectile dysfunction is the most common reason that aging couples stop having sex.³⁷ At least half of women over age 50 are no longer sexually active because of lack of a functional sexual partner.³⁸ Being sexually active and functional at cancer diagnosis increases distress about new sexual problems in men and women.^{39, 40}

Cancer treatments with a high risk of sexual dysfunction include intensive chemotherapy, total body irradiation, graft versus host disease after allogeneic transplant,⁴¹ treatments leading to abrupt ovarian failure in premenopausal women,³⁰ pelvic radiation therapy,⁹ radical pelvic cancer surgery in men,^{4–6, 42} chemoradiation for pelvic tumors,⁴³ anti-androgenic therapy for prostate cancer,³² and aromatase inhibitors for breast cancer.⁴⁰ Although penile and vulvar cancers are rare in Western nations, radical surgery removing major areas of genital tissue obviously also causes problems.^{44, 45} Vaginal reconstruction for advanced cervical or rectal cancer often fails to restore women’s sexual pleasure.⁴⁶

Psychosocial or behavioral factors also contribute to cancer-related sexual problems. Patients with a history of sexual abuse or trauma may have difficulty coping with cancer treatment, especially if the malignancy is in the reproductive system.⁴⁷ Relationship conflict and poor communication is also associated with poor sexual outcomes.⁴ Traditional beliefs on masculinity and suppression of emotion may contribute to deterioration of sexual function after treatment for prostate cancer.⁴⁸ Both men and women scoring high on neuroticism, a personality trait involving depression and anxiety, have higher rates of sexual problems after cancer.^{49, 50}

Prevention—surgical, medical, behavioral

Modifications of cancer surgery to prevent sexual dysfunction have included sparing autonomic nerves near the prostate,^3–6 not only during radical prostatectomy but also in radical cystectomy or surgery for colorectal cancer.^{42, 51} Enhancement has had limited results, as has avoiding damage to accessory arteries to the penis during pelvic surgery.⁵² Animal research and theoretical models support penile rehabilitation after surgery, using treatments for erectile dysfunction to promote penile blood flow, but benefits on recovery of erections in humans are unclear.²⁷ Nerve-sparing in radical hysterectomy has little impact on female sexual function.²⁶ Tissue-sparing surgery has been used instead of partial penectomy to treat localized penile cancer⁴⁴ or substituted for radical surgery in women for vulvar cancer,^{45, 53} but a majority of patients still have major sexual problems. Breast conservation or reconstruction also has few advantages over mastectomy in preserving women’s sexual pleasure and desire.²

Cancer treatments that preserve ovarian function in younger women, such as conservative surgery for low-grade ovarian cancer⁵⁴ or local therapy alone for ductal carcinoma in situ,⁵⁵ leave most women with normal sex lives. Intensive chemotherapy increases sexual dysfunction in both men³³ and women,⁵⁶ but less toxic regimens rarely achieve equivalent survival benefits. One exception is treating early-stage Hodgkin lymphoma with nonalkylating chemotherapy.⁵⁷ The trend toward personalized medicine and use of biological response modifiers may eventually lessen sexual morbidity, but little information is yet available on their sexual side effects.

Behavioral strategies may help prevent cancer-related sexual problems. Staying sexually active or stretching genital tissues with vacuum erection devices or vaginal dilators may prevent atrophy.^{27, 58, 59} Counseling that promotes more open sexual communication, and continued, noncoital sexual intimacy, certainly may prevent a loss of satisfaction within a couple’s relationship or a reduction in sexual self-esteem.^{60, 61}

Screening

Patients should be screened for sexual concerns and problems across the continuum of cancer care. During treatment planning, potential damage to sexual function from cancer treatment should be explained, including a mention of any conservative treatments. Although most patients rank survival over sexuality, a few would risk poorer cancer control for a treatment that would preserve sexual function. During treatment and at follow-up visits, sexual function should be monitored, at least with a periodic question, for example: “Sexuality is one important part of quality of life. Do you have any questions or concerns today about changes in your sex life since your cancer treatment?” In a study of patients in palliative care, about half wanted to continue sexual activity, despite a very high prevalence of sexual problems.⁶² In 2013, a new National Comprehensive Cancer Network survivorship guideline recommended systematic screening for sexual dysfunction by interview or questionnaire, followed by further evaluation and referrals for treatment. Although the guideline was categorized under survivorship, it includes patients at any point of care.⁶³

A brief questionnaire can be used to screen for sexual dysfunction. The National Cancer Institute sponsored creation of the Patient-Reported Outcomes Measurement Information System (PROMIS) Brief Sexual Function profiles for men and women. These multiple choice questionnaires with 8 and 10 items, respectively, can be administered as an entire scale or using computer adaptive software, only by asking relevant items.⁶⁴

Diagnosis

Because sexual dysfunction is most typically measured by self-report, diagnostic nomenclature has been varied and controversial.⁶⁵ Many labels do not help clinicians in choosing evidence-based treatments for problems. It is helpful to categorize sexual problems as affecting the following:

• ability to desire sex and experience subjective arousal
  
• ability for the genitals to engorge with blood during sexual arousal (i.e., erection in men and vaginal lubrication and expansion in women)
  
• ability to experience a satisfying orgasm
  
• problems with pain interfering with sexual pleasure
  
• urinary or fecal incontinence during sex

Most people treated for cancer have more than one specific sexual problem. For example, a woman who had chemoradiation for localized cervical cancer may have vulvovaginal atrophy and vaginal stenosis, causing dryness and acute pain with sexual caressing or penetration. As a result, her desire for sex and ability to reach orgasm are also impaired. A man may be unable to get or keep firm erections after radical prostatectomy. Urine may also drip from his penis with arousal and at orgasm. If he uses a medical treatment for erections, he may realize that his penis has shrunk in size or developed a curvature.⁶⁶ These problems lead him to avoid sex.

Taking the time to elicit a full description of the patient’s sexual problems remains the most important aspect of diagnosis. For women, a pelvic examination with attention to pain and atrophy on the vulva and inside the vagina is crucial.⁶⁷ For men with erectile dysfunction, urologists may conduct a color duplex ultrasound imaging studies of the penis, before and after injecting drugs to create an erection.⁶⁸ Such testing may identify venous insufficiency due to atrophy of the erectile tissue, which can limit the efficacy of oral medication or penile injection therapy. However, many urologists prescribe treatments empirically for erectile dysfunction, starting with oral medication and proceeding if necessary to penile injection therapy, a vacuum device, or a urethral suppository, with a penile prosthesis as the final step.⁶⁹ In many aging men, cardiovascular disease complicates the treatment of cancer-related sexual problems.⁷⁰

Prognostic factors

Only a few prognostic factors for sexual rehabilitation have been identified. Men or women who were not sexually active before cancer diagnosis are unlikely to seek help after cancer, unless they had previously sought treatment for their problems.^{37, 40} Younger men who start out with normal erections are more distressed and likely to seek help after surgery for prostate cancer.⁷¹ Having a partner who still enjoys sex is also crucial.⁷² For women, being in a sexual relationship is key to help-seeking.⁴⁰

Poor general and sexual communication are barriers to success with cognitive-behavioral treatment of sexual problems.¹³ In fact, couples with troubled relationships are less likely to enter clinical trials of sexual counseling.^{73, 74} Research on treatment outcomes is not available for people who are single or in a same-sex relationship.^{75, 76}