Treatment of Sexual Problems in People With Cancer
Although research is beginning to clarify the frequency and types of sexual problems people with cancer experience, few treatment programs for sexual dysfunction in cancer patients have been designed or tested. Programs that integrate medical and psychological modalities aimed at the treatment of sexual dysfunction in those who have had cancer are warranted. Additionally, these programs must be cost-effective and accessible to people with cancer.
Many patients are fearful or anxious of their first sexual experience after treatment and can often begin a pattern of sexual avoidance. If the patient is concerned about sending mixed signals to his or her partner, this can lead to avoidance of general intimacy and touch. The partner may also contribute to the generalized avoidance of intimacy through his or her reluctance to initiate any behavior that may be perceived as pressure to be more intimate or may contribute to any potential physical discomfort from greater expression of physical intimacy. Providers need to reassure patients and their significant others that even when intercourse is difficult or impossible, their sex lives are not over. The couple can give and receive pleasure and satisfaction by expressing their love and intimacy with their hands, mouths, tongues, and lips. Providers may encourage the couple to express affection in alternative ways (e.g., hugging, kissing, nongenital touching) until they feel ready to resume sexual activity. The couple will be encouraged to communicate honest feelings, concerns, and preferences.
If a man cannot attain an erection firm enough for penetration, and/or if intercourse is painful for a woman, some couples may be willing to find alternative ways to bring each other to orgasm and express sexual intimacy. Sensate focus exercises of noncoital pleasuring,[1,2] based on principles of sensuous massage, give couples an experience of sexual expression that allows them to be physically close and intimate without pressure and anxiety that can be associated with anticipation of intercourse. The structure and ground rules of sensate focus can help bypass performance anxiety (self-consciousness and self-evaluation) and enable the couple to lose themselves in the current experience of pleasurable touch. These exercises also help the couple communicate about potentially problematic or emotionally sensitive areas of the body. Providers may determine a couple’s openness to modification of their sexual technique.
As many patients will experience anticipatory anxiety about re-establishing sexual intimacy with their partner and potential uncertainty of their own sexual response, the potential advantages of self-stimulation can be explored. Self-stimulation has the advantage of allowing the individual to become comfortable with his/her sexual response and arousal without the added pressure of performance anxiety commonly heightened by concern for his/her partner’s pleasure, reactions, concerns, and/or fears. For many individuals, a cognitive reframing of masturbation to self-stimulation or self-pleasuring allows the individual to accept this activity as part of the process in sexual rehabilitation. For others, this behavior may still be a resilient and persistent taboo for cultural and religious reasons.
For those couples who wish to have sexual intercourse, sexual positions that place no weight on a scar or ostomy and positions that allow better control of depth of penetration can be explored. The side-by-side position (spooning) in which the man is behind the woman, or the L-shaped position, with both partners lying down, torsos at right angles and legs entwined, are two possibilities. Comprehensive pamphlets on sexuality and cancer, for both men  and women, provide illustrations of sexual positions and other self-help information.
For patients with colostomies or ileostomies, pamphlets are available from national organizations related to resuming sexual activity including topics such as sex and the female ostomate, sex and the male ostomate, and gay and lesbian ostomates. Providers can educate patients on limiting food intake before anticipated sexual activity, watching the types of food consumed, and planning times for intimacy when a bowel movement is less likely. Although the ostomy pouch is typically changed when about one-third full, patients should be taught to empty the pouch sooner when anticipating sexual intimacy. Patients may fear that the ostomy bag will interfere with sexual intimacy, become dislodged, or cause damage to the stoma. An empty and flat ostomy bag will not become dislodged from the stoma and can be rolled up or taped down so that it will not get in the way of sexual intimacy. Decorative covers may also be worn.[5,6][Level of evidence: IV] A wide selection of products for ostomates is available, including disposable pouches, reusable pouches that empty from the bottom or top while still attached, pouches with filters to control odors, and pouches that hang sideways instead of down for physical activity. Patients concerned about potential odor can use deodorant tablets or liquids in the bottom of the pouch or as recommended by the manufacturer.
Providers can help educate couples by offering practical suggestions to overcome changes in responsiveness to sexual stimulation. Couples should allow plenty of time for sexual expression with sufficient foreplay to develop the fullest possible sexual arousal. For some couples, early morning may be a good restful time for sexual expression. Conditions that facilitate sexual pleasure should be explored and may include relaxation, dreams, fantasy, deep breathing, and recalling positive experiences with the partner.
Erection problems are the most common sexual dysfunction for which men seek help after cancer treatment. Many men with erectile dysfunction are able to have an orgasm with oral or manual stimulation; many partners are satisfied and orgasmic with noncoital stimulation. If the desire for intercourse remains, there are several treatment options available for erectile dysfunction, depending on the cause and degree of dysfunction. Only a small percentage of men with erection problems seek help.[7,8]
With the advent of sildenafil (Viagra), a phosphodiesterase-5 (PDE-5) inhibitor used to treat erection problems, the percentage of men who seek treatment for erection problems has increased. Despite the publicity about the effectiveness of sildenafil, the drug works best in men with the mildest forms of erectile dysfunction. Many men will be unable to achieve adequate erections by taking this drug alone. The use of sildenafil enables about 72% of men with nerve-sparing prostatectomy and 15% of men with non–nerve-sparing prostatectomy to achieve erections sufficient for vaginal intercourse.
Radical prostatectomy can result in nerve injury, in addition to vascular and smooth muscle damage. Injury and prolonged flaccidity of the penis can result in hypo-oxygenation of the penile tissue, further complicating structural integrity and compromising future erectile function. The process of healing after surgery takes approximately 3 to 6 months, and full recovery can be expected at 1 year postsurgery. However, during this time, it is important for men to continue to have erections to keep the tissue healthy with adequate blood flow and to improve their future ability to have adequate erections. Therefore, early penile rehabilitation is recommended.
In one nonrandomized study, 84 men who had undergone nerve-sparing radical prostatectomy could choose whether to start early rehabilitation or to wait. In this study, early rehabilitation was defined as beginning activities to achieve erections within 6 months of radical prostatectomy, while delayed rehabilitation was defined as starting such activities more than 6 months after radical prostatectomy. Rehabilitation consisted of the use of sildenafil citrate, 100 mg, on four occasions. If erection sufficient for vaginal penetration was not achieved, then men were encouraged to use penile injections to obtain erections. Those who responded well to sildenafil citrate continued using this agent. Forty-eight men chose early rehabilitation, and 36 men chose delayed rehabilitation. The men were matched for age, comorbidities, and baseline erectile function, with a mean age of 58 years. Outcomes were evaluated with the International Index of Erectile Function (IIEF) and were assessed presurgery and at 1 and 2 years postsurgery. Trends for better scores on the IIEF were seen at 1 year, but statistically significant differences were not realized until year 2, with significantly more men in the early rehabilitation arm having unassisted functional erections (48% vs. 33%) and more men in the early group having functional erections with sildenafil (76% vs. 45%). Twenty-four percent of men in the early rehabilitation group had normal erectile function scores as measured by the IIEF, compared to 8% of men in the delayed rehabilitation group.[Level of evidence: II] Some data suggest that about 12% of sildenafil responders lose efficacy by 3 years.[Level of evidence: III]
In a study of brachytherapy in the treatment of localized prostate cancer, sildenafil improved potency in 62% to 70% of patients. Patients who were not being treated with androgen therapy had a significantly better response. Similarly, of men who became impotent after brachytherapy for prostate cancer, 85% to 88% responded with improved erectile function when taking sildenafil. Reported potency rates after prostate brachytherapy are high; a 3-year follow-up study demonstrated that 80% of patients were able to have erections adequate for satisfactory sexual activity with or without sildenafil.[Level of evidence: II] Sildenafil has also improved erectile function for patients with partial parasympathetic nerve disruption from rectal surgery.[Level of evidence: I][Level of evidence: II] No other treatment for erectile dysfunction has a high rate of patient acceptance. Sildenafil has been studied in a novel primary prevention modality using nightly administration after a bilateral nerve-sparing prostatectomy. This approach effected a sevenfold improvement in return of spontaneous, normal erectile function 2 months after discontinuation of the drug.[Level of evidence: IV] The authors state that this effect appears to be mediated by properties unique to sildenafil that include improved endothelial function and neuronal regeneration and neuroprotection.
Published data also suggest that early use of sildenafil after radical retropubic prostatectomy may preserve intracorporeal smooth muscle content;[Level of evidence: II] although this effect on the return of potency is not known, maintaining the pro-erectile ultrastructure is integral to rehabilitating erectile function after radical retropubic prostatectomy. Data on the efficacy of early postoperative erectile treatment rely on very few randomized trials. Because the natural recovery of erectile function has been reported to take as long as 2 years, larger randomized trials with at least 2 years of follow-up are needed before definitive conclusions can be drawn about the true efficacy of rehabilitative sexual therapy for postoperative erectile function.
Three PDE-5 inhibitors approved by the U.S. Food and Drug Administration (FDA) are on the market:
- Viagra (sildenafil).
- Levitra (vardenafil).
- Cialis (tadalafil).
Although all three of these oral medications are PDE-5 inhibitors, they are not the same. No trials have been published that compare sildenafil, vardenafil, and tadalafil. It appears that all three agents are similar in efficacy, helping 60% to 70% of patients with erectile dysfunction.[Level of evidence: I][24,25] However, comparisons of the efficacy of the PDE-5 inhibitors are complicated by the heterogeneity of the populations studied, the varied primary cancer therapies employed, different timing in measuring outcomes in the clinical trials, and variance in the endpoints used to determine efficacy. Furthermore, most of these trials were industry sponsored.
The major contraindications for use of a PDE-5 inhibitor are concurrent use of nitrates or the alpha-blockers terazosin (Hytrin) and doxazosin (Cardura). The major difference in the three approved inhibitors is that tadalafil has a considerably longer serum half-life, which provides both a larger window of opportunity and potential side effects.[24,25]
Because it was approved in 1998, there is far more research on the use of sildenafil than on the use of the other PDE-5 inhibitors in oncology patients; vardenafil and tadalafil were approved in 2003. Tadalafil was investigated in the treatment of erectile dysfunction following bilateral nerve-sparing radical retropubic prostatectomy. Results from this randomized, double-blind, placebo-controlled, multicenter study found that 71% of patients randomly assigned to receive tadalafil reported improved erections.[Level of evidence: I] Vardenafil had been investigated in the treatment of erectile dysfunction after radical retropubic prostatectomy and following nerve-sparing radical prostatectomy.[27,28][Level of evidence: I]
In post–radical retropubic prostatectomy patients, the average intercourse success rate per patient receiving 20 mg of vardenafil was 74% in men with mild to moderate erectile dysfunction and 28% in men with severe erectile dysfunction, compared with 49% and 4% for placebo. Patients receiving 10-mg and 20-mg doses of vardenafil following nerve-sparing radical prostatectomy reported significantly greater intercourse satisfaction, orgasmic function, and overall satisfaction rate with hardness on the IIEF, compared with those receiving placebo.
Therapies such as penile injections, vacuum devices, or intraurethral medication have extremely high dropout rates, and of men who seek help at clinics for erectile dysfunction, only about one-third feel long-term satisfaction, despite trying a mean of two different treatment modalities.[29-31][Level of evidence: II] For men who have a suboptimal response to oral therapies after radical retropubic prostatectomy, the use of combined intracorporal injection (ICI) and a PDE-5 inhibitor has been shown to improve erectile function. One retrospective study found that among men who experienced erectile dysfunction after nerve-sparing retropubic prostatectomy, 68% who combined ICI with either sildenafil or vardenafil reported improved erectile function. On follow-up, 36% of these patients used ICI therapy only intermittently, as they reportedly felt that this was adequate for good results.[Level of evidence: III]
Rates of long-term satisfaction are superior for penile prosthesis surgery,[34-36] but with less invasive and permanent treatments available, fewer men choose this treatment modality, particularly after undergoing intensive cancer therapy. The role of the man’s partner in prompting him to try a treatment or to keep on using it is also poorly understood. When erectile functioning is impaired, counseling will initially focus on obtaining sexual pleasure and satisfaction without erections or intercourse. For men with postsurgical erectile dysfunction, there is the possibility for improved function over time as nerves may potentially regenerate for up to 2.5 years after surgery. Providers may educate patients that opting to use no medical intervention to restore erections is also a valid choice. Comprehensive reviews of the current management of erectile dysfunction are available.[38-42] Also, several authors [39,43,44] provide further discussion on the management of inhibited sexual desire and other male sexual dysfunctions.
When women experience changes in arousal, most notably vaginal dryness and irritation, vaginal moisturizers (e.g., Replens) and water-based lubricants (e.g., Astroglide and K-Y Liquid) may be suggested, especially in women who cannot use estrogen replacement. The approval of the estradiol-releasing vaginal ring (Estring), containing a slow-release preparation, 2 mg of micronized 17-beta-estradiol, may also provide a less risky alternative to systemic estrogen replacement for women with postmenopausal vaginal atrophy.[Level of evidence: I] Estring has demonstrated a decreased recurrence of urinary tract infections in postmenopausal women and a significant maturing effect on vaginal and urethral mucosal cells, decreasing the urogenital symptoms of postmenopausal women.[Level of evidence: I]
Another alternative to local estrogen replacement is the first-available 25-μg 17-beta-estradiol vaginal tablet (Vagifem). A study comparing Vagifem tablets with 1.25-mg conjugated equine estrogen vaginal cream (Premarin) found both to be equivalent in relieving symptoms of atrophic vaginitis, with patients who received Vagifem experiencing less endometrial proliferation or hyperplasia. This study also found that women rated vaginal tablets more favorably than vaginal cream.[Level of evidence: I] The long-term safety of the use of vaginal estrogens by women who should avoid estrogens has not been determined.
If changes in arousal are also associated with the endocrine changes of menopause, the option and evaluation of hormone replacement may be discussed. Some women may experience discomfort with penetration around the vaginal entrance and can learn to relax the pubococcygeus muscles with Kegel exercises.[38,49,50] Women who have lost vaginal depth or caliber as a result of pelvic surgery, radiation therapy, or graft-versus-host disease may also benefit from a program of inserting vaginal dilators of gradually increasing sizes, and at the same time, learning exercises to better relax the muscles surrounding the vaginal entrance.[38,51] Some women may also benefit, at least in the short term after cancer treatment, from lubricant or anesthetic gels to prevent pain in tender, dry vulvar areas.[Level of evidence: I]
The FDA approved a nonpharmaceutical device to aid sexual arousal in women. The EROS clitoral therapy device (EROS-CTD) creates a gentle suction over the clitoris to increase blood flow and sensation. This device is only available by prescription and is clinically indicated for the treatment of female sexual dysfunction. It is expected to be particularly effective in postmenopausal women, women who have had hysterectomies, and those women who have surgically induced menopause. The efficacy of EROS therapy has been supported by several small pilot studies,[Level of evidence: III][55,56] one of which specifically examined its efficacy in alleviating the symptoms of sexual dysfunction among women with a history of irradiated cervical cancer.[Level of evidence: II] Three months posttherapy, this study found statistically significant improvements in all domains evaluated, which included increased sexual desire, arousal, lubrication, orgasm, sexual satisfaction, and reduced pain. Additionally, follow-up gynecological examinations revealed improved vaginal elasticity, mucosal color, and moisture and decreased bleeding and ulceration. Randomized controlled trials are warranted to fully assess the benefits of EROS therapy.
More specific information for the evaluation and treatment of female sexual dysfunction, including painful intercourse (i.e., dyspareunia), vaginismus, inhibited orgasm, and sexual arousal and desire disorders, is available in other resources.[39,49,57,58]
For both men and women, a persistent and complex sexual problem is loss of desire for sex after cancer treatment. In men who have not had prostate cancer and have clinically low levels of serum testosterone, replacement by injection or patch is often effective in restoring normal sexual function. Testosterone replacement tends to have little effect, however, if given to a man whose own hormone levels fall within the normal range. Safety, dosage, and delivery systems for androgen replacement in women need to be studied. Numerous studies have evaluated the use of transdermal testosterone in various populations.[59-65][Level of evidence: I] These populations include women who have hypoactive sexual desire disorder who have had oophorectomies, who are naturally postmenopausal, who are premenopausal, and who have a history of cancer. These studies used doses ranging from 150 μg to 10 mg daily. Most of the studies in women have used concomitant estradiol supplementation if estrogen levels fell outside the normal premenopausal range and found that testosterone supplementation significantly improved libido outcomes.
Only two published studies have evaluated transdermal testosterone for libido in postmenopausal women without estrogen supplementation. One of these studies was in cancer survivors, and the other was in postmenopausal women who were diagnosed with hypoactive sexual desire disorder.[Level of evidence: I] The clinical trial in cancer survivors showed that in 150 female cancer survivors randomly assigned to receive either 10 mg of transdermal testosterone daily or placebo for 4 weeks, there was no statistically significant difference in improvement in sexual desire as measured by a validated sexual function scale, the Changes in Sexual Functioning Questionnaire, despite the fact that androgen levels improved significantly in the women receiving the testosterone but remained unchanged in the women receiving placebo. The other clinical trial randomly assigned 814 postmenopausal women to receive either 150 µg or 300 µg of transdermal testosterone versus placebo for a year (without estrogen), with an efficacy endpoint of 24 weeks looking at satisfying sexual episodes captured in activity logs. Authors reported a significant improvement of about one additional satisfying sexual episode over a 4-week period in the 300-µg group compared with placebo, but not in the 150-µg group. Upon further analysis, it was found that women who had experienced surgical menopause, having had their ovaries removed, did not benefit from this intervention. This raises the questions of whether ovarian status in women who have been treated for cancer with chemotherapy is more like surgical or natural menopause, and whether the chemotherapy-induced menopausal ovary functions with an active stroma or has no activity after chemotherapy, akin to surgical removal. Research in this area is needed to better understand the entire hormonal milieu of women after cancer treatment and how all of the hormone changes work together to impact symptoms. Therefore, it is not clear that testosterone alone, in the absence of estrogen, can positively impact libido.
For women who have breast cancer, the safety of giving androgens is unknown. Serum androgens can be aromatized to estrogen. Data from epidemiologic studies suggest there may be an increased risk of breast cancer with higher concentrations of endogenous androgens.[68,69] However, endogenous androgens present over a life span do not equal exogenous androgen supplementation for a woman with low androgen concentrations. One small study evaluating the effects of testosterone supplementation on breast tissue found that the addition of testosterone to estrogen and progesterone inhibited the breast proliferation exhibited in the group that received estrogen, progesterone, and placebo.[Level of evidence: I] Furthermore, one case-controlled study in more than 8,000 women found that the use of exogenous testosterone for 4 years did not result in an increased incidence of breast cancer, despite the fact that 83% of testosterone users were also using estrogen replacement compared with only 15% of the age-matched controls.[Level of evidence: III] Therefore, many unanswered questions remain about sufficient androgen levels for adequate sexual function as well as short- and long-term safety. To date, there are no compelling data to support the use of testosterone alone to improve libido in women who are estrogen deficient.
Because loss of desire often is multifactorial, an approach that includes psychological assessment and treatment is usually optimal. An experienced mental health professional can rule out a mood disorder as a factor in loss of desire and can explore the interactions of factors such as the following:
- Changes in relationship dynamics.
- Loss of physical well-being.
- Changes in sexual self-concept.
- Negative body image.
The effects of prescription medications, chemical dependency, or hormonal abnormalities can be recognized and targeted for change. Unfortunately, there is no true aphrodisiac medication that can restore sexual desire in the presence of a normal hormonal environment.
In general, a variety of treatment modalities are available for sexual dysfunction after cancer. For many problems, providing information and suggestions for behavior change in a self-help format may be sufficient. Education can be provided via books, pamphlets,[3,4] CD-ROMs, videos, peer counselors,[Level of evidence: I] or Internet interactions. For men and women with more complex and severe problems, professional intervention will be more effective. Future research needs to explore which treatment components are most effective with particular groups of patients. A psychoeducational intervention was evaluated in women with a history of breast cancer.[Level of evidence: I] The intervention content addressed the following:
- Sexual anatomy.
- Body image.
- Attitudes and behavior.
- Ways to enhance sexual function.
The intervention was delivered in person, in groups, at 2-hour sessions over a 6-week period. The primary outcome was the Mental Health Index, providing a measure of anxiety, depression, loneliness, distress, well-being, and positive affect. Other outcomes included sexual satisfaction, self-image, and functioning, such as dyspareunia. Women were identified through a mailed survey and randomly assigned ahead of time either to the intervention or to the control group (written material only). Women randomly assigned to the intervention were then invited to participate. Of 284 women assigned to the intervention, only 83 agreed to participate; of those, only 72 attended any of the sessions. The most common reasons for declining participation were inconvenient time and/or location, being too busy, or feeling that the intervention was not needed. One hundred twenty-seven women were randomly assigned to the control group, and follow-up was reported for 98 of them.
Results from this study are presented for three groups:
- Control group.
- Intervention nonparticipants.
- Intervention participants.
An intent-to-treat analysis showed no significant differences between groups for the Mental Health Index. However, there was an intervention effect for general satisfaction with sex. An as-treated analysis did suggest improvement on the Mental Health Index, with women who reported more distress at baseline experiencing more benefit. This study provides data to support the idea that interventions focusing on psychosocial and cognitive factors may be an important component of interventions to improve emotional and sexual outcomes. However, more research is needed to develop psychoeducational interventions that are less time intensive, can be disseminated easily, and are more readily accepted by cancer survivors.
Sexual counseling can be provided for individuals, couples, or groups. The effectiveness of these different formats has not been compared for people with cancer. It is also not known whether brief counseling can enhance the impact of medical treatments, such as those used to overcome erectile dysfunction or dyspareunia. There is limited research about the impact of support groups on sexual outcomes for men with prostate cancer.[Level of evidence: II] It is likely that associations between better outcomes and participation in support groups reflect baseline sociographic and clinical differences between those who participate in support groups and those who do not.Current Clinical Trials
Check NCI’s list of cancer clinical trials for U.S. supportive and palliative care trials about sexuality and reproductive issues and sexual dysfunction that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.References
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