Psychological Impacts of Male Sexual Dysfunction in Pelvic Cancer Survivorship

Abstract

Introduction:

A common negative sequela of cancer treatment in men is sexual dysfunction, which can have a significant psychological impact and can contribute to feelings of depression, anxiety, and other mental health issues. Management of cancer survivors’ psychological and mental well-being plays an important role in the treatment and recovery process.

Aim:

This review aims to identify how sexual dysfunction impacts the lives of male cancer survivors and to provide clinicians with treatment recommendations specific to this patient population.

Methods:

A total of 51 peer-reviewed publications related to sexual dysfunction in male cancer survivors were selected for analysis. Sources were chosen based on relevance to current cancer therapies, causes and psychological impacts of sexual dysfunction, and treatment recommendations for clinicians caring for cancer survivors. PubMed search terms included: “sexual dysfunction”, “cancer survivorship”, and “male cancer survivors”.

Main Outcome Measures:

Measures of sexual dysfunction were based on cancer survivors reporting inadequate erectile capacity for penetrative sexual intercourse, decreased sensitivity of the genitalia, or inability to enjoy sex.

Results and Conclusions:

Sexual dysfunction was present in male cancer survivors from diverse ages, cancer diagnoses, and treatments of cancer. Many men surveyed presented with psychological distress resulting from their post-treatment sexual dysfunction. This had a significant negative impact on their sexual self-esteem, body image, and mental health. Sexual and social development was delayed in survivors of childhood cancer. Healthcare practitioners should initiate conversations with patients regarding the potential for sexual dysfunction at the time of cancer diagnosis and throughout treatment and follow up. Physical symptoms of sexual dysfunction should be treated, whenever possible, using phosphodiesterase 5 inhibitors or other interventions, and all cancer survivors presenting with psychological distress related to sexual dysfunction should be offered professional counseling.

Introduction

The National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program reports that 291,350 men in the United States were diagnosed with a form of pelvic cancer in 2018, with prostate cancer being the most prevalent. The 5-year survival rates of these cancers range between 65-100%.[1-7] The National Cancer Institute Division of Cancer Control and Population Studies estimates that there were 15.5 million cancer survivors in the United States as of January 2016. This number is projected to increase to 20.3 million by 2026 and to 26.1 million by 2040, representing an increase of nearly 11 million people since 2016.[8]

Surgery, chemotherapy, and radiation therapy are often used to treat cancer. Sexual dysfunction is a common negative outcome of these treatments, resulting from damage to nervous or reproductive tissues. Nerve sparing surgical procedures and targeted radiation therapy are used to help mitigate the frequency and severity of sexual dysfunction, but complete avoidance of these negative effects is not possible with current therapies.[9-11]

The primary psychological effects of sexual dysfunction in male cancer survivors include a decreased sense of self-worth, loss of personal identity, concern for future reproductive capacity, and struggles maintaining intimate relationships. These feelings can promote a sense of depression and anxiety as well as decrease levels of sexual enjoyment and satisfaction.[12-14] The mental health status of cancer survivors experiencing sexual dysfunction should be carefully monitored. In this review, we summarize the literature examining how sexual dysfunction impacts the lives of male cancer survivors and provide clinicians with treatment recommendations specific to this patient population.

Materials and Methods

A review of peer-reviewed publications was conducted to understand the psychological impacts of sexual dysfunction on male cancer survivorship. A total of 51 studies were selected from the PubMed database and analyzed. These studies were selected based on their relevance to current cancer therapies, causes of sexual dysfunction, psychological effects associated with lack of sexual function, and treatment recommendations for clinicians caring for cancer survivors. PubMed search criteria to obtain these sources included: “sexual dysfunction”, “cancer survivorship”, and “male cancer survivors”.

Cancer Therapies and Sexual Dysfunction

Current treatments for pelvic cancers include surgery, chemotherapy, and radiation therapy, all of which can negatively impact patients’ sexual function. Helgason et al. surveyed 53 Swedish prostate cancer survivors who had undergone external beam radiation therapy using the Radiumhemmet Scale of Sexual Functioning. The study observed that 91% of men reported reduced ejaculate volume, 77% reported decreased sexual desire, 77% reported decreased erection stiffness, and 47% reported decreased orgasmic pleasure demonstrating that sexual dysfunction has both physical and psychological components.[15]

Techniques to minimize the effect of oncologic therapies on sexual function are increasingly used, though these remain imperfect. Cavernous and sympathetic nerve sparing surgical approaches are utilized when tumors do not involve the neurovascular bundle.[9] Avoidance of thermal and electrical energy damage can minimize vascular injury and limit cavernous nerve impairment by reducing cavernous ischemia and preserving the cavernous nerves.[16, 17]

Avulova et al. conducted a Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) population study of 991 male prostate cancer survivors in order to assess the effectiveness of nerve sparing surgery in preserving sexual function. The study reported that men who underwent a bilateral nerve sparing procedure had significantly greater sexual function 3 years post-treatment than men who underwent unilateral or no nerve sparing.[11] However, despite nerve sparing, sexual dysfunction often persists. Korfage et al., in a sample of 314 prostate cancer survivors, reported that the incidence of erectile dysfunction (ED) 12 months after treatment was 88% for men undergoing radical prostatectomy with nerve sparing and 54% following external beam radiation.[18] Additionally, Basal et al. retrospectively analyzed the medical records of 203 patients who underwent bilateral nerve sparing for radical prostatectomy and found that 47.3% still had some degree of ED an average of 17.4 months after surgery. The study reported that factors such as thermal damage, ischemic injury, mechanically-induced nerve stretching and local inflammatory effects of surgical trauma may injure the cavernous nerves and result in ED.[19] These studies are just some of many which provide evidence that cancer survivors continue to face significant challenges long after their cancer has been resolved.

Desai et al. published the first study to compare robotic-assisted-laparoscopic radical prostatectomy (RALP) vs. open radical prostatectomy (ORP) in the Veteran's Affairs (VA) hospital setting. The authors reported that among the 91 ORPs and 153 RALPs, patients undergoing RALP procedures had significantly lower incidence of the number of blood transfusions (1.3% vs 40%, p<0.001), length of stay, urine leak (1.3% vs 12.1%, p<0.001), and ICU readmissions (0% vs 3.3%, p<0.001) as compared to patients undergoing ORP. As such, the authors concluded that RALP procedures are safe to introduce in the VA setting without compromising outcomes.[20]

Hoppe et al. observed, in a small study of 20 men diagnosed with low- to intermediate-risk prostate cancer that patients receiving proton beam therapy are unlikely to develop azoospermia as a result of scatter radiation to the testis. However, ejaculate volume is likely to decrease and the pH and quality of sperm may be negatively affected.[10]

A cross-sectional, population-based survey of 780 Dutch prostate cancer survivors by Mols et al. reported ED in 74% of radical prostatectomy patients and 67% of external beam radiation patients, compared to 18% in the general population, demonstrating the significantly higher prevalence of sexual dysfunction in cancer survivors.[21]

Androgen deprivation therapy (ADT) and the resulting lack of circulating testosterone can contribute to metabolically adverse changes in body composition.[22] Harrington et al. surveyed 132 prostate cancer survivors treated with ADT in a convenience sample using two established questionnaires, the Body Image Scale and the Quality of Life Index-Cancer Version. The authors reported that there was a significant correlation between body image dissatisfaction and diminished quality of life in prostate cancer survivors treated with ADT as compared with prostate cancer survivors who were not treated with ADT.[23]

Impacts of Childhood Cancers

Radiotherapy and Testosterone Levels

In children and adolescent cancer patients, the impact of radiation therapy on endocrine function is highly dependent on the child’s age, the total dose of irradiation, and the number of fractions given. If less than 12 gray (Gy) are delivered to the testes, testicular Leydig function will likely be preserved. Doses in excess of 30 Gy will cause testosterone deficiency later in development.[24]

Sexual Sequelae of Childhood Cancers

In a longitudinal survey of 291 adult survivors of childhood cancer, Bober et al. analyzed the late effects of childhood cancer treatments on future sexual function. The authors observed that lack of interest in sex (30%), difficulties enjoying sex (24%), and difficulties being aroused (23%) were the most commonly reported sexual sequelae from the survivors’ cancer treatments. Additionally, 19% of male participants reported difficulties with erection and 29% of female participants reported problems achieving orgasm. These sexual dysfunctions were not correlated with type of cancer treatment or type of malignancy. In this sample, female survivors of childhood cancer were twice as likely to report sexual dysfunction than their male counterparts.[25] Frederick et al. reported similar findings after interviewing a small cohort of 22 young adult survivors of childhood cancers who reported two or more problems with sexual function following treatment. In this survey, 91% of survivors reported psychological issues interfering with sexual activity, 86% reported difficulties relaxing and enjoying sex, and 73% reported difficulties becoming sexually aroused.[12]

Fears of Judgement

Survivors in the Frederick et al. study expressed concern regarding how their partners would react to knowledge of their cancer history; forming a significant barrier to intimate relationships. Other respondents feared being judged or pitied by their sexual partners.[12]

Social Development

Vannatta et al. indicated that a diagnosis of a malignancy during childhood can have a particularly negative effect on social development.[26] Vannatta et al. surveyed 49 pediatric cancer survivors, 82 of their teachers, and 2,504 of the survivor’s classmates in a longitudinal study to investigate the impact of pediatric cancer diagnoses and treatments on the survivors’ social development. The surveys indicated that male cancer survivors under age 10 were less likely to be liked by peers, had fewer friends, and were more likely to be perceived by classmates as socially isolated. Findings in this study were not significant for pediatric female cancer survivors or for male survivors in adolescence.[26]

Delayed Milestones

Assessing cancer survivors in a slightly older age group, van Dijk et al. surveyed 60 Dutch survivors of childhood cancer using the Medical Outcome Study-Short Form (MOS-SF-36) and a 40-item questionnaire related to psychosexual and social functioning designed for the study. The authors reported that male cancer survivors treated in adolescence had a delay in achieving psychosexual milestones including dating, touching under clothes, and sexual intercourse as compared to those treated in childhood. Female survivors of childhood cancer were also delayed in these developmental areas, as well as age in which they began masturbating.[27] These findings suggest that the age of pediatric cancer diagnosis and treatment may be significant in determining which social or psychosexual developmental behaviors are most likely to be delayed.

Stam et al. demonstrated that normal development is delayed in childhood cancer survivors as compared with peers by evaluating Course of Life questionnaires from 363 adult survivors of childhood cancer compared with 508 age-matched peers without a history of cancer. This study observed that cancer survivors achieved fewer milestones than their peers with respect to autonomy-, social-, and psycho-sexual development or achieved these milestones later relative to their peers.[28] Delayed development of sexual identity is also affected by the negative body image formed by cancer survivors during treatments.[29] This negative perception of body image can be due to physical features which sometimes accompany cancer treatments, such as stretch marks or scars. In addition, shortened height or delayed puberty can result from treatment of malignancies and may result in poor self-esteem as well as greater feelings of isolation or being different from peers.[12, 29]

Infertility

Concerns, and in some cases shame, about infertility are particularly prominent among adolescent or young adult survivors of childhood cancer.[12] Crawshaw interviewed 28 adult survivors of childhood cancer with a prognosis of diminished fertility and found that many men had lower social confidence and were hesitant to discuss their fertility status with their partners due to fears of being rejected.[30] This finding is supported by the work of Frederick et al., as more than half of adolescent male participants voiced anxiety about infertility. Even when told they were not at increased risk for infertility, some young men still expressed concerns.[12]

Mental Health Concerns

Hudson et al. analyzed health data from 9,535 adult long-term survivors of childhood cancer in comparison with 2,916 of the survivors’ siblings to assess the impacts of childhood cancer relative to a control group. The authors found that after a mean interval of 17.4 years from time of diagnosis to completion of the questionnaire, 17.2% of survivors reported behaviors consistent with either depression, somatization, or anxiety compared with 10.2% of siblings. Anxiety as a result of cancer treatments, 13.2%, was the most prevalent adverse impact on survivors’ mental health which was measured by the study.[31] The Bober et al. study also reported a higher incidence of anxiety and depression among childhood cancer survivors relative to childhood cancer survivors without sexual dysfunction.[25] These findings demonstrate that a cancer diagnosis during childhood or adolescence can have an enduring impact on the mental health of the survivor.

Changes in Orgasm and Ejaculation

Changes in orgasm are commonly reported by cancer survivors. Frey et al. conducted a cross-sectional study of 256 sexually active Danish men who underwent radical prostatectomy using a series of validated questionnaires including the International Index of Erectile Function (IIEF), International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and a previously non-validated Danish Translation of the Erection Hardness Score. A significant number of subjects reported anorgasmia (5%), decreased orgasm intensity (60%), delayed orgasms (57%), and pain during orgasm (10%) a median of 17 months after surgery. Additionally, 38% of survivors reported urinary incontinence during sexual activity, and 25% reported sensory changes in the penis.[32]

Problems with ejaculation have been linked with psychological disorders in men of all ages.[33, 34] Huyghe et al. surveyed 241 sexually active men who underwent permanent prostate brachytherapy (PB) using the IIEF-5 questionnaire to assess the severity of sexual dysfunction in this population. The authors reported that although 81.3% of men had preserved ejaculatory function after PB, the number of patients with rare or absent ejaculatory function was double the pretreatment number (p < 0.0001). In addition, 18.7% of participants reported dry ejaculations, whereas none reported dry ejaculations prior to PB.[35] Dry ejaculations can be psychologically distressing, as many men associate orgasm and ejaculation as a combined entity.

Psychological Impacts of Sexual Dysfunction (Figure 1)

Figure 1:

Psychological impacts of cancer-related male sexual dysfunction

Perceived Loss of Masculinity

Sexual dysfunction is perceived by cancer survivors and others as a loss of masculinity. For many, the social construct of masculinity parallels with the ability to impregnate a partner.[30] However, even men who were not concerned about fertility expressed shame at their perceived loss of masculinity. Romero et al. surveyed a small cohort of 18 penile cancer survivors who had undergone partial penectomy and reported that 50% of these patients did not resume penetrative sexual relations as a result of their shortened penis, despite having adequate erectile and reproductive capacities.[36]

Zaider et al. surveyed 75 prostate cancer survivors and their partners and found that men who perceive loss of masculinity following cancer treatments, regardless of their level of sexual function, are more likely to be distressed by ED. Thirty seven percent of respondents reported feeling that they had lost part of their manhood, 35% that they were not the man they used to be, and 29% feeling as if they were no longer a whole man.[37] Albaugh et al. confirmed Zaider’s findings in a study surveying 27 prostate cancer survivors and their partners to assess the psychological impacts of sexual dysfunction. The men in Albaugh’s study equated ED to “feeling like less of a man” and stated that it made them feel abnormal or unnatural.[14] Ussher et al. interviewed 124 prostate cancer survivors identifying as gay or bisexual and reported similar findings as Zaider and Albaugh, with men in their sample relating their post-treatment ED to “not feeling whole” or being “cheated” out of a core aspect of their masculinity. Additionally, men in this study reported undergoing a sexual identity crisis following cancer treatments.[13]

Risk of Depression

Nelson et al. surveyed 339 prostate cancer survivors a mean of 3.9 years from time of diagnosis to evaluate the relationship between prostate cancer and depression. The authors reported, based on multivariate analysis, that erectile function was a significant predictor of depression.[38] Presenting similar findings, the Albaugh et al. study of prostate cancer survivors observed that the majority of men surveyed reported psychological distress including depression, anxiety, and suicidal ideation resulting from post-treatment sexual dysfunction.[14]

Impact on Gay and Bisexual Males

The degree to which cancer survivors are psychologically distressed regarding their sexual dysfunction can be compounded by social factors. Men identifying as gay and bisexual in the Ussher et al. study experienced loss of erectile function and ability to engage in penetrative sex at rates comparable with prostate cancer survivors in the general male population.[13, 39, 40] Ussher et al. conducted an additional study comparing the psychological impacts of sexual dysfunction of 124 gay and bisexual male prostate cancer survivors to 225 heterosexual male prostate cancer survivors. In this comparison, the authors found that men who identified as gay and bisexual had lower self-esteem and satisfaction with treatment as well as significantly higher psychological distress, cancer-related distress, and ejaculatory concern.[41]

Additionally, the Ussher et al. study of gay and bisexual prostate cancer survivors indicated that 61% of respondents rated their ED as a moderate or big problem which had a “great emotional impact” and was “depressing”, “very difficult”, “an enormous loss”, or a cause of “great sadness”.[14] Of this cohort, many men reported that, to them and others in the homosexual community, ED signifies aging and thus promotes feelings of failure and inadequacy. This label has negative connotations within gay male culture, where youthfulness and normal sexual function are highly valued.[13] Some gay and bisexual men in the Ussher et al. survey stated that their sexual dysfunction forced them to “reinvent [themselves]” sexually. This process of adapting to new sexual roles contributed significantly to the feelings of inadequacy and loss of sexual identity expressed by the men in this study.[13]

Katz-Dizon Model

The Katz-Dizon Model of male sexuality after cancer is a comprehensive biopsychosocial model which considers numerous factors influencing sexuality for men after cancer.[42] This model proposes that a man’s sex drive is heavily influenced by societal messages about the concept of masculinity and how male performance are envisioned. This sex drive is strongly linked to a man’s sexual performance, which is also determined by commonly critical feedback from the sexual partner regarding their personal degree of sexual satisfaction. The subsequent body changes following cancer treatment and related prescription medications often alter a man’s body image, which can negatively impact the man’s sex drive and performance. This perception of negative body image associated with cancer or treatments can endanger the effectiveness of communication between cancer patients and their current or future sexual partners.

Patient and Partner Expectations

Symon et al. surveyed 50 prostate cancer survivors who underwent either radical prostatectomy (n=24) or external beam radiotherapy (n=26) to assess the correlation between the survivors’ pre-treatment expectations and post-treatment outcomes. The authors reported that pre-treatment expectations of post-treatment outcomes were 22.5% greater (p<0.0001) than observed sexual domain scores a year following treatment indicating that the patients were overly optimistic about their future sexual outcomes.[43]

These overly optimistic expectations of sexual outcomes are frequently shared by the survivors’ sexual partners. Wittman et al. interviewed 20 prostate cancer patients and their partners preoperatively and 3 months postoperatively to assess the role of couples in the recovery process of cancer survivors experiencing sexual dysfunction. The authors reported that, preoperatively, 90% of couples expected the men to recover to their preoperative level of erectile function despite being educated on the potential for nerve damage and a lengthy erection recovery period of up to 2 years. However, post-operatively, 75% of the men felt that ED diminished their manhood, 50% mourned the loss of sexual performance, and 25% reported loss of sexual confidence. The preoperative over-optimism of couples was rooted in the association of factors such as surgeon skill, healthy living, and willingness to work diligently towards recovery; unfortunately, these factors are only somewhat relevant in determining degree of postoperative sexual functioning.[44] These findings demonstrate that couples are largely unprepared to cope with the realities of cancer treatment on sexual function, despite efforts by practitioners to educate patients and set reasonable expectations.

The couples captured by the Wittman et al. study experienced grief both after cancer diagnosis and following surgery. Feelings associated with grief, frustration, and hopelessness were reported by 80% of the couples. Even though the majority of couples preoperatively expressed confidence in their ability to cope with anticipated postoperative sexual function challenges, 80% of couples postponed thinking about the recovery process.[44] Thus, planning and mental preparation may help to decrease the degree of grief and loss experienced by cancer survivors and their partners.

Treatment Recommendations

In February 2018, the American Society of Clinical Oncology (ASCO) released updated clinical practice guidelines for treatment of cancer survivors experiencing sexual dysfunction.[45] Several of the primary recommendations include:

• Phosphodiesterase Type 5 inhibitors (PDE5i) should be used to treat erectile dysfunction (Table 1).

• Discussion of sexual function should be initiated by the provider and conducted with the patient throughout the treatment and recovery process.

• Patient and their partner should be provided with access to resources or referral information.

• Psychosocial counseling should be offered to all individual patients and couples desiring to improve relationship and intimacy issues including sexual function and satisfaction.

Table 1:

Phosphodiesterase Type 5 Inhibitors [74-77]

Drug	Dose	t1/2	Time to Peak, Plasma	Time to Take Before Sex
Avanafil	100 mg once daily (50-200 mg; should use lowest dose to achieve desired effect)	5 hr	Fasting: 30-45 min After High-fat Meal: 1.12-1.25 hrs	~15 min
Sildenafil (Revatio; Viagra)	50 mg once daily	4 hr	Fasting: 30-120 min (Oral)	1 hr (range: 30 min–4 hr)
Tadalafil (Adcrirca; Cialis)	As needed (An): 10 mg (range: 5-20 mg as tolerated) Once daily (Od): 2.5 mg once daily at approximately the same time each day (range: 2.5-5 mg as tolerated)	15-17.5 hr	2 hr (range: 30 min-6 hr)	An: 30 min Od: No regard for timing of sexual activity
Vardenafil (Levitra; Staxyn)	10 mg once daily	4-6 hr	0.5-2 hr	1 hr

Sexual Aids

Phosphodiesterase Type 5 Inhibitors

Phosphodiesterase Type 5 inhibitors are commonly prescribed as a treatment for ED. Tsertsvadze et al. analyzed 130 randomized, controlled trials of PDE5i to assess clinical utility and risks and concluded that sildenafil, vardenafil, and tadalafil are equally effective. However, the manufacturer of tadalafil sponsored three of four randomized, controlled trials directly comparing these PDE5i, introducing a potential bias.[46]

Avanafil is a PDE5i that was approved by the US Food and Drug Administration (FDA) in April 2012.[47] Burke et al. analyzed 3 randomized, double-blind, placebo-controlled clinical trials of avanafil to assess its efficacy and safety for clinical use as a PDE5i. The authors reported that avanafil has sufficient efficacy for clinical use and has a faster onset of 15 minutes compared to other FDA approved PDE5i. In vitro data suggest that avanafil has more selectivity for PDE5 compared to the other PDE5i. This may result in fewer vision changes and other side effects that have been reported with other PDE5i, which are less specific to PDE5.[48]

Risks of PDE5i

There are a number of risks associated with use of PDE5i’s. Sildenafil can cause temporary visual changes such as blue tinged vision, increased sensitivity to light, and blurred vision.[49] Additionally, clear cautions and contraindications about the use of PDE5i in patients with cardiovascular comorbidities and patients taking nitrates have been indicated.[50] Giannetta et al. performed a recent meta analysis of 1,622 subjects randomized to either PDE5i or placebo to determine the effects of PDE5i on cardiac morphology and function. The authors reported that subjects treated with PDE5i experienced an anti-remodeling effect by reducing cardiac mass in subjects with left ventricular hypertrophy (LVH), an increasing end-diastolic volume in non-LVH subjects, and improved cardiac performance by increasing cardiac function and ejection fraction.[51] Studies have demonstrated that mild and moderate hepatic impairment significantly decrease oral clearance and increase maximum concentration, area under the curve, and drug half-life for sildenafil and vardenafil, but not tadalafil.[49, 52]

Although there are some reports of priapism and hearing loss, Giuliano et al. analyzed 67 double-blind placebo-controlled trials of sildenafil with over 14,000 men and reported that there was no causal link between sildenafil and cardiovascular events, priapism, hearing loss, or non-arteritic anterior ischemic optic neuropathy (NAION). The authors also noted that overdose with sildenafil was rare in the ED population.[53] The data for this analysis were provided by Pfizer, the manufacturer of sildenafil, thus representing a potential bias.

A modestly increased risk of melanoma has been reported in studies of subjects using PDE5i.[54, 55] However, reports of causation between PDE5i and sun exposure resulting in melanoma are conflicting.[54, 56]

When postoperative ED is anticipated, use of PDE5i can be started in the preoperative setting. Beginning a regimen of PDE5i daily immediately following radical prostatectomy may help to decrease penile length loss. Montorsi et al. conducted a double-blind placebo-controlled trial with 423 prostate cancer survivors randomized to either 5mg tadalafil once daily, 20mg tadalafil on demand, or placebo. The authors reported that, after 9 months of follow up, only subjects taking 5mg tadalafil once daily yielded a significantly reduced loss of penile length compared to placebo, with a mean difference of 4.1mm.[57] No clinical trial data currently support an expedited return of erectile function with the use of PDE5i’s.

Accessibility of PDE5i Medications

Healthcare practitioners should be aware of the wide range of costs of medications such as PDE5i and testosterone, particularly with patients who lack insurance coverage or whose insurance does not cover such medications. Of the most commonly prescribed PDE5i’s, sildenafil is generally the most affordable, given that a generic formulation is available.[58] The inability to afford medications or access healthcare resources can further compound the anxiety and frustration of patients and enhance the degree of underlying stress.

Mishra et al. recently evaluated the price variability of PDE5i at different types of pharmacies. The authors analyzed 331 pharmacies in the same geographic region which were classified as chain (CVS, Walgreens, Rite Aid), wholesale (Sam’s Club, Costco), independent, or hospital-affiliated. Comparing variable costs of sildenafil, the authors reported a 1,189% price difference between independent and hospital-affiliated pharmacies and a 928% price difference (p<0.001) between independent and chain pharmacies, with independent pharmacies being the most affordable.[59]

Alternatives to PDE5i Therapies

ASCO recommends that vacuum erection devices (VEDs), medicated urethral systems for erection, or intracavernosal injections be used as adjunct therapies in patients who lack responsiveness to PDE5i. Furthermore, VEDs should be used daily to prevent loss of penile length [45]. Preservation of penile length or faster restoration of erectile function may result from use of these therapies sooner after cancer treatment, although this remains to be definitively determined. Introduction of these interventions prior to treatment may be beneficial to some men.[45]

Inflatable penile prosthesis (IPP) should be considered when patients lack responsiveness to less invasive therapies such as PDE5i, VEDs, and intracorporal injections. These devices allow patients with ED to resume penetrative sexual intercourse without interfering with urination, ejaculation, sensation, or orgasm.[60] The introduction of InhibiZone antimicrobial coating comprised of the antibiotics minocycline and rifampin has drastically reduced the once-common infection rates of IPP patients.[61, 62] Carson retrospectively compared patient data from 2,261 men with InhibiZone-coated IPP to 1,944 men of similar age and etiologies with non-coated IPP and reported that the antimicrobial treated group had an infection rate that was 82.4% lower than the control group after 60 days and 57.8% lower after 180 days.[61, 62] Carson et al. more recently retrospectively analyzed IPP revision rates due to infection in 39,005 men with first-time IPP over 8 years and reported that the rates of revision in the antimicrobial treated group was 1.1% compared to 2.5% (p<0.0001) in the non-treated group.[63]

Discussion of Sexual Dysfunction with Affected Men

Clinicians are strongly encouraged to initiate the discussion of possible sexual dysfunction with the patient at the time of cancer diagnosis and continue to inquire about the patient’s level of sexual function periodically during treatment and recovery.[45] Nearly all of the participants of the Frederick et al. study reported not having discussions with their physicians regarding sexual function. When discussion did occur, it was typically limited in scope, with focus on the use of protection and safe sex practices. Both male and female participants in the study expressed a strong desire to discuss sexual health with their medical providers including relevant topics such as dating, developing relationships, body image, and disclosing cancer history to partners.[13]

The 27 prostate cancer survivors in the Albaugh et al. study recommended that information be provided before, during, and after cancer treatment. These men commented that patients may lack sufficient understanding or may not be mentally prepared to process all of the information upon first learning of their cancer diagnosis.[15] This study observed that patient experiences are improved when patients feel that the physician devotes the time to provide information and answer questions. Reports of poor patient experiences are commonly associated with the belief that the physician was overly optimistic about sexual function outcomes. Additionally, some men in the study felt they were not adequately informed about the effects of treatment on their sexual function and thus felt unprepared to cope following treatment. Several of these participants stated that they regretted having their procedure done.[15] These findings demonstrate the importance of setting clear expectations starting at the time of cancer diagnosis and continuing to discuss sexual function throughout the treatment and recovery process.

Sperm Banking

Sperm banking is recommended for men with cancer before proceeding with surgery, chemotherapy, or retroperitoneal or pelvic radiotherapy. Girasole et al. studied the effects of sperm banking prior to cancer treatments on future fertility of testicular cancer survivors and found that men who banked sperm were less likely to have had children before cancer diagnosis and more likely to have children after treatment compared to survivors who did not bank sperm.[64] Ginsberg et al. analyzed data from 68 male cancer patients to assess the benefits of sperm banking and observed that the semen quality of men was dramatically reduced by just one course of gonadotoxic therapy.[65] This finding demonstrates the importance of offering sperm banking prior to therapy, particularly in men undergoing chemotherapy.

Access to Resources

Zhou et al. surveyed 615 prostate cancer survivors 3 to 8 years after treatment to assess their physical and psychological health as well as their information interests and preferences related to the late effects of cancer treatment. These survivors desired information related to coping with sexual dysfunction (64.1%), side effects (52.2%), and emotional problems (27.2%). The authors did not, however, specify whether participants preferred receiving this information before or after cancer treatment. The study reported that 77.4% of men with low sexual function desired information on sexual health and function, whereas only 66.8% of men with good sexual health desired the same information (p=0.004).[66] The study further observed that male cancer survivors desired information on sexual health and function from either their oncologist, primary care provider (PCP), or from the internet or written resources. However, survivors strongly desired information regarding their emotional health primarily from their PCP, preferring their PCP over their oncologist 4-fold.[66] These data suggest that survivors may not directly associate their post-treatment emotional health status with the physical consequences of their cancer treatment.

Flynn et al. utilized the Patient-Reported Outcomes Measurement Information System (PROMIS) Sexual Function measure to survey data on communication between 819 oncology professionals and 109 cancer patients and survivors. Of these participants, 74% of cancer patients and survivors believed that discussions with oncology professionals about sexual problems was important, yet the degree of information provided regarding sexual function varied by cancer type. The authors reported that patients and survivors who received information on sexual function from their oncology professionals was highest for prostate cancer (79%) followed by colorectal (39%) and lung cancer (23%).[67] This discrepancy identifies an important communication gap between oncology professionals and cancer patients and survivors, particularly among those individuals being treated for non-pelvic cancers.

Psychosocial and Psychosexual Counseling

Kowalkowski et al. surveyed 85 male and 32 female bladder cancer survivors and noted that while nearly half of participants reported the usefulness of talking with partners about sexual function, only one-fifth reported sharing all their concerns with their partners.[68] These findings demonstrate the difficulty some cancer survivors face in communicating their feelings related to sexual dysfunction and maintaining intimacy with their partners. Sexual therapists are trained professionals which can help cancer survivors feel more comfortable addressing and discussing these sensitive topics.

ASCO recommends that PDE5i be used along with psychosocial and/or psychosexual counseling during treatment of cancer-related sexual dysfunction (Figure 2).[45] Professional psychosocial/psychosexual counseling should be offered to all patients with cancer, with the goal being to improve sexual response, body image, intimacy and relationship issues, and overall sexual functioning and satisfaction. For men with partners, counseling should be directed at the couple. The inclusion of partners, while important during assessment, should not be automatic, but based on the findings of a comprehensive assessment as well as the desires of the cancer survivor.[45] However, sexual rehabilitation can be most successful if both partners participate in a recovery plan that responds to both partner’s needs.[69] Most insurances, including Medicare, cover sexual health assessment and treatment under mental health services.

Figure 2:

Treatment algorithm for male cancer patients with sexual dysfunction

Although mental health/sexual health practitioners are integrated into the continuum of care in some cancer centers, Albaugh et al. noted that the offering of comprehensive mental health services is beyond the scope of practice for most urology practices. Having a strong referral network of mental health professionals and sexual therapists will improve the quality of care and provide a team-based approach.[15] The American Association of Sexuality Educators, Counselors, and Therapists (AASECT) is an excellent resource for connecting healthcare providers with professional sexual therapists across the United States. ASCO’s Expert Panel acknowledged that additional education concerning changes in erection capacity and alternative ways to maintain intimacy may be required for gay and bisexual men.[45]

Antidepressant Medications

Specific medication recommendations for treating mental health diagnoses, such as depression and anxiety, in cancer survivors who also have sexual dysfunction are not included in the updated ASCO clinical guidelines.[45] It is appropriate to refer cancer survivors experiencing psychological distress to a mental health professional for psychological evaluation and counseling. The need for mood-altering medications can be assessed at this time and be prescribed if appropriate.

Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly prescribed for treatment of depression. However, the use of SSRIs frequently contributes to many aspects of sexual dysfunction, including decreased libido, ED, and orgasmic and ejaculatory disorders. There are some indications that antidepressant-emergent sexual dysfunctions do not resolve upon cessation of the medication and can persist indefinitely in some individuals, so caution should be exercised when prescribing these medications.[70]

However, not all antidepressants share the same sexual sequelae. Koshino et al. analyzed the effects of Wellbutrin on 569 patients diagnosed with Major Depressive Disorder (MDD) based on criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. The authors reported that there were no significant findings in regards to sexual dysfunction, weight change, and withdrawal symptoms in patients treated with Wellbutrin.[71] Thus, Wellbutrin should be considered as a first-line antidepressant therapy in populations with sexual dysfunction.

Mindfulness Therapy

Bossio et al. recently conducted a pilot study to assess the feasibility of utilizing mindfulness as a therapy for situational ED. The authors surveyed a small sample of 10 individuals diagnosed with situational ED who engaged in formal 4-week mindfulness therapy sessions as well as in-home mindfulness exercises and found that the participant’s IIEF subscale score improved between pretreatment and 6 months following treatment; although the degree of improvement was not statistically significant.[72] However, additional studies implementing mindfulness as a therapy for cancer patients with ED are needed. While mindfulness therapy may not have a strong impact on sexual function which is organic, it may reduce anxiety regarding sexual performance and maximize the man’s ability to function at an optimal level.

Maintaining Intimacy

Maintaining intimacy in the setting of ED is a struggle which impacts many cancer survivors and their partners. Couples struggling to maintain intimacy following treatment of cancer should be encouraged to meet with a sexual therapist.

Along with striving to overcome the physical challenges associated with ED, couples should focus on strengthening their relationship and physical affection for each other through means other than sexual intercourse. It may be necessary for couples to expand their sexual repertoire by engaging in non-penetrative sexual activities such as manual stimulation, deep kissing, or oral sex.[69] The use of alternative sexual methods can allow the couple to maintain intimacy, even if challenges with ED and loss of libido persist.

Walker et al. evaluated 59 prostate cancer survivors and their partners using a one-time couples’ intimacy workshop in order to assess the effectiveness of this intervention. The authors surveyed these couples at baseline and two months following the workshop through the Revised Dyadic Adjustment Scale and Sexual Function questionnaire to assess the outcomes of relationship adjustments and sexual function. The authors reported that patients and partners who participated in this workshop showed improvements in relationship satisfaction. Furthermore, small-to-medium effect improvements were noted regarding sexual function, but these improvements were not statistically significant after adjusting for multiple comparisons.[73]

Areas for Future Research

There is a paucity of research examining the psychological impact of sexual dysfunction in cancer survivors from minority or multi-cultural groups, particularly those from lower socioeconomic backgrounds or those lacking education. Most current adult studies of sexual dysfunction in male cancer survivorship have focused on a relatively homogenous group of Caucasian, educated males. The psychological and social impacts of prostate cancer survivors presenting with sexual dysfunction are well documented. However, more research is needed on the psychological impact of other pelvic and non-pelvic cancer diagnoses in male cancer survivorship. There is also a need for additional longitudinal studies exploring how a childhood or adolescent cancer diagnosis and associated treatment impact survivors throughout their lifetime. Further research on the effectiveness of alternative therapies such as mindfulness, in treating aspects of sexual dysfunction, is needed.

Analysis Limitations

Limitations of this review include using data from two publications of male cancer survivors with sexual dysfunction in the Dutch population as well as one study from both the Danish and Swedish populations. It is thought that these data can be applied to cancer survivors in other countries, but differences in culture may result in variation between populations. Additionally, the scope of the present review is focused on sexual dysfunction in male cancer survivors and does not include studies exclusive to female cancer survivors or to populations with sexual dysfunction without a cancer diagnosis.

A significant limitation of many sources utilized in this review is a small sample size, with 6 of the included studies evaluating fewer than 30 individuals. Also, many of the studies involved interviewing cancer patients, survivors, or their partners and could potentially be biased.

Conclusions

Sexual dysfunction commonly results from cancer therapy, irrespective of the type of therapy, and potentially impacts over 15.5 million Americans and their partners. Sexual dysfunction after cancer therapy is frequently the result of damage to cavernous or sympathetic nerves to male genital tissues or gonadotoxicity and can result in symptoms of ejaculatory dysfunction, low sexual desire, ED, and orgasmic dysfunction. While nerve sparing surgical procedures and targeted radiation therapy strive to preserve reproductive capacity and sexual function in cancer patients, sexual dysfunction persists in many cancer survivors. This can have a significant and lasting psychological impact on survivors’ sexual identities as well as adolescent social and psychosexual development. In fact, many patients undergo a sexual identity crisis following cancer treatment. Many male cancer survivors feel a deep sense of loss and a degradation of their masculinity as a result of their sexual dysfunction which can create a profound sense of psychological distress. The degree of psychological distress among cancer survivors experiencing sexual dysfunction should be closely monitored as there may be an increased risk of depression, anxiety, and even suicidal ideation in this population.

Healthcare professionals should initiate conversations with their patients regarding the potential for sexual dysfunction throughout cancer treatment and follow-up. Doing so may help patients set appropriate expectations of managing their sexual dysfunction and may reduce the level of psychological distress. ASCO recommends that physical causes of sexual dysfunction, such as ED, should be treated using PDE5i or VEDs. Men can benefit from combining these therapies with psychosocial counseling aimed at improving sexual response, body image, intimacy and relationship issues, and overall sexual functioning and satisfaction. Professional counseling and therapy services should be offered to all cancer patients struggling with the psychological impacts of sexual dysfunction. For men with partners, psychosocial counseling should be directed at the couple.