Lauren M. Walker

Androgen Deprivation Therapy for Prostate Cancer: Recommendations to Improve Patient and Partner Quality of Life

INTRODUCTION Because of improved prostate cancer detection, more patients begin androgen deprivation therapy (ADT) earlier and remain on it longer than before. Patients now may be androgen deprived for over a decade, even when they are otherwise free of cancer symptoms. AIM An ADT Survivorship Working Group was formed to develop and evaluate interventions to limit the physiological and emotional trauma patients and their partners experience from this treatment. METHODS The multidisciplinary Working Group met for 2 days to define the challenges couples face when patients commence ADT. A writing sub-group was formed. It compiled the meetings proceedings, reviewed the literature and, in consultation with the other members of the working group, wrote the manuscript. MAIN OUTCOME MEASURES Expert opinion of the side effects of ADT that affect the quality of life (QOL) of patients and their partners and the recommendations for managing ADT to optimize QOL were based on the best available literature, clinical experience, and widespread internal discussions among Working Group members. RESULTS Side effects identified as particularly challenging include: (i) body feminization; (ii) changes in sexual performance; (iii) relationship changes; (iv) cognitive and affective symptoms; and (v) fatigue, sleep disturbance, and depression. Recommendations for managing ADT include providing information about ADT side effects before administration of ADT, and, where appropriate, providing referrals for psychosocial support. Sexual rehabilitation principles for persons with chronic illness may prove useful. Psychological interventions for sexual sequelae need to be offered and individualized to patients, regardless of their age or partnership. Support should also be offered to partners. CONCLUSIONS Our hope is that this plan will serve as a guide for optimizing how ADT is carried out and improve the lives of androgen-deprived men and their intimate partners.

The Unique Needs of Couples Experiencing Androgen Deprivation Therapy for Prostate Cancer

Androgen deprivation therapy (ADT) is being increasingly used to treat men with prostate cancer. ADT has been associated with many side effects that may persist for the lifetime of the patient and can have potentially devastating effects on the quality of life of both men and their intimate relationships. Despite U.S. estimates that more than 40,000 men begin ADT each year and live on average for 10 years, there have been few studies examining the effect of ADT on couples. This article reviews the emerging literature on the challenges faced by men and their partners while undergoing ADT. Loss of libido, erectile dysfunction, genital shrinkage, low self-esteem, and diminished masculinity are commonly associated with undergoing ADT. These losses frequently lead to changes in the marital relationship in areas such as roles and responsibilities, communication, and intimacy. Intervention strategies for helping couples maintain a strong relational bond need to be selected carefully for this population because of these unique and profound changes. Couples who succeed in maintaining sexuality and intimacy have been shown to have higher quality of life and more satisfying relationships.

A description of heterosexual couples' sexual adjustment to androgen deprivation therapy for prostate cancer.

Objective: It is estimated that 600 000 men are currently living in North America with castrate levels of testosterone as a result of androgen deprivation therapy for prostate cancer. The goal of this study was to explore how patients and their partners adjust to changes associated with androgen deprivation therapy (ADT).

Psychological effects of androgen-deprivation therapy on men with prostate cancer and their partners.

The clinical benefits of androgen‐deprivation therapy (ADT) for men with prostate cancer (PC) have been well documented and include living free from the symptoms of metastases for longer periods and improved quality of life. However, ADT comes with a host of its own serious side effects. There is considerable evidence of the adverse cardiovascular, metabolic, and musculoskeletal effects of ADT. Far less has been written about the psychological effects of ADT. This review highlights several adverse psychological effects of ADT. The authors provide evidence for the effect of ADT on mens sexual function, their partner, and their sexual relationship. Evidence of increased emotional lability and depressed mood in men who receive ADT is also presented, and the risk of depression in the patients partner is discussed. The evidence for adverse cognitive effects with ADT is still emerging but suggests that ADT is associated with impairment in multiple cognitive domains. Finally, the available literature is reviewed on interventions to mitigate the psychological effects of ADT. Across the array of adverse effects, physical exercise appears to have the greatest potential to address the psychological effects of ADT both in men who are receiving ADT and in their partners. Cancer 2015;121:4286–99.

Patients and partners lack knowledge of androgen deprivation therapy side effects

OBJECTIVE Androgen deprivation therapy (ADT) is the primary treatment for advanced prostate cancer (CaP). There is growing evidence that ADT negatively affects mens psychosocial well-being (e.g., causing sexual dysfunction, bodily feminization) and physical health (e.g., increasing the risk of osteoporosis and metabolic syndrome). Although strategies for managing the majority of side effects exist, it is not clear that patients are benefiting from this knowledge. METHODS Seventy-nine newly prescribed ADT patients and 54 of their partners were given a checklist of various common and uncommon ADT side effects. They were asked to indicate the drug side effects that they had heard of or anticipated. RESULTS Both patients and their partners were poorly informed about the side effects of luteinizing hormone-releasing hormone (LHRH) agonists used for ADT. More than 70% did not know that anemia, memory problems, loss of body hair, and depression can occur following treatment. Over 50% were unaware of significant potential side effects such as reduced muscle mass, osteoporosis, increased fracture risk, weight gain, genital shrinkage, and gynecomastia. Concurrently, more than 20% mistakenly anticipated dizziness and itching. CONCLUSION The lack of awareness of ADT side effects may partially explain why ADT currently results in significant decreases in the quality of life of patients and their partners. Patients uninformed about side effects do not engage in behaviors to prevent or reduce the risk of adverse effects. Improved efforts to educate patients about treatment side effects and coping strategies may result in improved psychosocial and physical health for CaP patients undergoing ADT.

Sexual Adjustment to Androgen Deprivation Therapy: Struggles and Strategies

More than half of all men with prostate cancer will be treated with androgen deprivation therapy (ADT) at some point during their lives. Though an effective treatment for prostate cancer, ADT results in profound changes in the man’s sense of masculinity and sexuality (e.g., erectile dysfunction, loss of libido, genital atrophy and severe genital shrinkage, hot flashes, loss of muscle mass, fatigue, bodily feminization). These changes usually result in the cessation of all sexual activity. Surprisingly, some couples do find ways of continuing to have satisfying sex despite the man’s castrate level of testosterone. Herein, we describe the sexual struggles that couples encounter when attempting to adapt sexually to ADT. A grounded theory methodology was used to analyze interview data. The successful strategies that couples used to overcome struggles, as well as those which seemed to exacerbate struggles, are documented. Couples adjusting to ADT might benefit from knowing which strategies are most likely to result in positive adjustment and which are not.

Psychosocial perspectives on sexual recovery after prostate cancer treatment.

Many therapies for erectile dysfunction (ED) after prostate cancer treatment improve erectile firmness, yet, most couples stop using aids within 1–2 years. Patients and partners who expect immediate and complete success with their first ED treatment can be demoralized when they experience treatment failure, which contributes to reticence to explore other ED aids. Comprehensive patient education should improve sustainability and satisfaction with ED treatments. Pre-emptive and realistic information should be provided to couples about the probability of recovering natural erections. Beginning intervention early and using a couple-based approach is ideal. Recommendations are provided about the timing of ED treatment, the order of aid introduction, and combination therapies. Renegotiation of sexual activity is an essential part of sexual adaptation. From the outset of therapy, couples should be encouraged to broaden their sexual repertoire, incorporate erection-independent sexual activities, and continue to be sexual despite ED and reduced libido.

Impact of androgen deprivation therapy on sexual function: a response.

Dear Editors, We appreciate the growing interest in sexual health for cancer patients and survivors. Mazzola and Mulhalls recent paper,1 however, creates the impression that rewarding sex is not possible for prostate cancer patients on androgen deprivation therapy (ADT). This impression, we believe, is not scientifically justified, and may be a disservice to prostate cancer patients and their partners in that it could act as a negative placebo, i.e., the opposite of an aphrodisiac. It was unfortunate that the authors did not use their paper to explore positive pathways for sexual interaction and arousal among ADT patients. Instead, readers may be left with a rather discouraging outlook on the prospect of sexual intimacy and pleasure for androgen-deprived cancer patients. Historically and culturally, there are data to show that castrated males are not obligatorily asexual. While most historical eunuchs were castrated before puberty, they were considered to be everything from asexual to hypersexual depending on the culture.2 Postpubertal eunuchs, whether the one million Hijra of India3 or the contemporary Westerners castrated (frequently by self-surgery) as treatment for Male-to-Eunuch gender dysphoria,4 continue to display both sexual interest and ability. Our data show that many modern-day voluntary eunuchs maintain not only sexual interest, but also sexual activity (manuscript in prep.). Of 203 adult males who were voluntary castrated (chemically or physically) and either used no hormone supplementation or took minimal estrogen to prevent osteoporosis and hot flashes, 4% reported an increase in sexual activity, either masturbation or with a partner, 24% reported no change and 45% reported some reduction in sexual activity. Only 27% reported becoming asexual, a result that many of them had sought. As reported previously,5 these men ranged in age from 18+ to their 80s, with a mean age in the mid-forties. Sexual function was self-reported in a brief questionnaire that we designed to acquire data on sexual fantasies, sexual attraction and sexual activity in the months before and after castration. Based on the information that the respondents provided us, we could assume that the vast majority of these men were functionally intact before being androgen-deprived. One contributing factor for androgen-deprived males to maintain sexual interests is likely to be estrogen supplementation. Wibowo et al.6 recently reviewed a wealth of animal studies showing that estrogen in androgen-deprived males raises libido above castrate levels. Furthermore, Wibowo et al. have now expanded this review to include castrated males of 27 species ranging from amphibians to mammals. Of these, 14 (13 mammalian) species exhibit elevated sexual interest following exogenous estrogen administration. This further strengthens the notion that androgen deprivation needs not terminally eradicate libido. We acknowledge, though, that this effect is not universal and differences between species could be attributable to innate species differences, differences in the type and dose of estrogen used and in the pathways used for estrogen administration. Estrogen can also preserve libido to some extent in cancer patients on ADT. Studies by Ellis and Grayhack (1963)6, Bergman et al. (1984)7, Davidson et al. (1983)8 and Brett et al. (2007)9 (all cited in Wibowo et al.10) collectively indicate that patients taking high-dose estrogen were more sexually active than those who were surgically castrated and receiving no supplemental hormones. Furthermore, libido is better preserved in prostate cancer patients on anti-androgen monotherapy (who subsequently have elevated estradiol levels from the aromatization of testosterone) than those who are surgically castrated.7 Wassersug and Gray12 independently noted that male-to-female transsexuals, who are castrated and take supplemental estrogen, are more likely to be sexually active than are androgen-deprived prostate cancer patients, who typically take no supplemental estrogen. These studies support the hypothesis that estrogen can elevate libido in androgen-deprived men. We recognize that this estrogenic effect is not as strong as androgens in promoting sexual interest. Additionally, as with testosterone itself, it is likely to be confounded by factors such as age and also whether the person was sexually active prior to ADT treatment. In addition, regardless of erectile functioning, androgen-deprived cancer patients need not be anorgasmic. Warkentin et al.13 published a case study of an androgen-deprived male who reported being orgasmic. We have recently obtained physiological data from the patient discussed in Warkentin et al.13 which confirm that there are spastic contractions in the patients pelvic floor synchronous with his reports of orgasm. It is noteworthy that patient uses an external penile prosthesis and his ability to achieve orgasms appears to be dependent on the multisensory integration of total body and not just genital stimulation. A discussion of this method for maintaining a satisfying sex life was unfortunately overlooked in both Mulhalls 2010 book Saving Your Sex Life: A Guide for Men with Prostate Cancer, and the current paper. Other studies have reported some prostate cancer couples maintaining a sex life while on ADT.14 The sample, although small, suggests that maintaining some level of sexual intimacy is both possible and satisfying. It should be acknowledged that humans are motivated to engage in sexual activity for a variety of reasons, not because of sexual urges alone.15 For example, despite a lack of libido, some patients remain sexual for the benefit of their partners. Assessments of libido do not necessarily equate with ability and/or motivation for maintaining sexual activity. In sum, there is far more to male sexuality than erectile function and libido, and lack of testosterone needs not inevitably eliminate pleasurable sexual experiences. Impressions, like the one made by Mazzola and Mulhall,1 about the hopelessness of maintaining a rewarding sex life may in fact contribute to the finding that many couples do abandon their sex lives after being told to expect failure.14 Sadly, none of the papers mentioned above are discussed by Mazzola and Mulhall.1 To ignore this literature is, we believe, a disservice to the many couples who are trying to maintain a rewarding sexual life in the presence of ADT.

Assessment of relational intimacy: factor analysis of the personal assessment of intimacy in relationships questionnaire

Cancer treatment often results in couples feeling less intimately connected. Psychosocial interventions have been developed to improve couples’ adaptation to these changes [1,2]. The Personal Assessment of Intimacy in Relationships (PAIR) is a commonly used measure of relational intimacy. Despite its use in cancer intervention research, it has yet to be validated within an oncology population. The PAIR [3] was developed as a 36-item scale containing five intimacy subscales: (i) emotional, experiencing understanding and the ability to freely express one’s emotions; (ii) social, sharing a social network and common friends; (iii) sexual, experiencing physical closeness; (iv) intellectual, experiencing a free and stimulated exchange of ideas; and (v) recreational intimacy, sharing leisure activities. The final subscale, conventionality, is used to detect response bias of ‘faking good’. Individuals are asked the degree to which they agree with each item on a 5-point Likert scale. The PAIR has been used in several studies aimed at assessing and improving relational and sexual intimacy in cancer populations [2,4]. Although the PAIR appears to be an ideal measure, problems exist in its current form. Its reliability is reasonable. Four subscales demonstrate adequate internal consistency (emotional α= 0.70–0.73, sexual α= 0.71–0.77, intellectual α= 0.70–0.80, and conventionality α= 0.71–0.80); however, two subscales demonstrate lower internal consistency (social α= 0.67–0.71 and recreational α= 0.55–0.70) [3,5]. Moore et al. [5] attempted to replicate the original factor structure [3] and found similar internal consistency for only four of the six subscales (emotional, sexual, intellectual, and conventionality). Even after removing the conventionality subscale, because as a validity index, it was thought to be unrelated to intimacy, factor structure replication was still poor. Thus, they proposed a 30-item PAIR with three subscales: (i) engagement, feeling connected with their partner; (ii) communication, experiencing open and fluent exchange of ideas; and (iii) shared friendships, participating in and enjoying interactions with friends [5]. All subscales demonstrated adequate to good internal consistency (α= 0.70–0.96). Despite improved reliability, they failed to confirm the threefactor structure in a sample of couples experiencing sexual dysfunction [5]. The purpose of this study was to assess the validity of the PAIR in prostate cancer (PCa) patients and their partners.

Supportive expressive group therapy for women with advanced ovarian cancer.

Abstract Supportive Expressive Group Therapy (SEGT) has been shown to enhance the well-being of women with breast cancer. However, its applicability for other cancer populations has yet to be determined. Critics assert that cancer support groups may be harmful, especially for patients with advanced disease. Two qualitative studies were conducted to assess the application of SEGT to women with advanced ovarian cancer. In Study 1, a qualitative analysis was conducted on participant interviews designed to evaluate SEGT in ovarian cancer populations by exploring both positive and negative experiences associated with SEGT. In Study 2, interviews with SEGT participants and their health care professionals were conducted and analyzed using a grounded theory analysis. Interviews explored how SEGT affected patients’ relationships with medical professionals. Results of Study 1 suggested that SEGT could be challenging to the participants in that it involved both the discussion of distressing emotions and the witnessing of group members’ suffering and death. However, though painful, the women generally perceived these emotions as part of the process of coming to terms with their cancer, and thus found SEGT helpful. Results of Study 2 revealed that, if initially misdiagnosed, women typically experienced feelings of anger and a loss of trust in health care professionals. SEGT was helpful in resolving anger and restoring trust by facilitating communication and increasing understanding. Oncology professionals perceived SEGT as enhancing patients’ ability to cope with cancer. Women with advanced ovarian cancer felt that the benefits of SEGT far outweighed the associated distress and potential for harm. The reported substantial positive outcomes countered criticisms that SEGT may have negative iatrogenic effects.