Disorders of Sexuality and Reproduction

Ursula S. Ofman

As the effectiveness of medical treatment of cancer patients has improved a great deal during the past decades, quality of life outcomes have gained increasing attention of clinicians and researchers alike. Although nerve-sparing surgeries, conformal radiation, and new chemotherapies have greatly contributed to improved survivorship, the psychological realities post cancer treatment remain somewhat oblique. Sexuality is a complex area, in which biology and psychology intersect, and which is also strongly affected by interpersonal and behavioral factors. Even if oncology were able to successfully treat patients without creating any physical impairments to sexual function, sexual dysfunction would be part of many a patient’s posttreatment life because of the severity of the psychological impact of cancer diagnosis and the experience of treatment on self image, confidence, attitude toward self and partner, and so on. After active treatment, survivors attempt to return to their previous daily routines. The challenge this represents for many cancer survivors is not trivial. Sexuality is one of the most complicated areas of functioning to regain. A diagnosis of cancer means having to face one’s own mortality, possibly for the first time. The treatments are often painful, frightening, and intrusive and have the potential to erode one’s sense of body integrity and body image. Memories of the illness and treatment together with their emotional aftereffects present a disruptive mix for sexual interest and functioning. These effects may continue long after active treatment is over and are “stirred up” again at every routine follow-up visit.

Many cancer treatments interfere physiologically with some aspect of physical functioning, which also may impede an easy return to pretreatment life. These disruptive, long-term effects are not only those that directly affect sexual organs or gonads but also include other aspects of functioning that may interfere with the patient’s sexual self-image, such as scars, a change in physique as a result of hormone treatment, ostomies, disfiguring surgery, and so on. Any change in appearance or functioning and any long-term treatment side effect can be a reminder of the illness and its treatment and may interfere with a sensuous, virile, and confident sexual self-image.

Changes in gender-role behavior resulting from the physical and emotional side effects of cancer surgery or treatment may not only impair the patient’s sexual interest, but also affect the partner’s perception of the patient as a sexual object. For both the patient and the patient’s partner, it may be difficult to view each other from the same perspective that had previously drawn them to each other sexually. The patient may have become physically and emotionally dependent on the partner, who in return may have had to assume a nurturing, parenting role. After treatment ends, it may be impossible to return to the previous role distribution in the relationship. Both partners are also faced with the varying reactions of extended family, friends, and colleagues to the illness and subsequent difficulties. These reactions may range from affectionate support to angry withdrawal, adding to the psychosocial difficulty of the posttreatment period. Worries about the possibility of a recurrence, together with uncertainty about the future, heightened anxiety and depression, a sense of personal inadequacy, and diminished sense of control in either or both partners also can interfere seriously with the resumption of a sexual life (1, 2, 3).

Despite the consistently documented negative effects of cancer and cancer treatments on sexual functioning, most cancer survivors continue to maintain a sexual self-image, even if it is difficult to integrate physical and emotional changes over time. Little has been done to identify the richness of patients’ attempts to integrate their cancer experiences into a new sexual self-concept. Research in this area has been hampered, among other factors, by methodological issues including the need for innovative approaches to solicit and measure responses (4, 5). Few studies to date document the outcomes of structured interventions to ameliorate sexual difficulties posttreatment. Sexual recovery is usually just one among several goals of the studied interventions. The studies reviewed reported improved sexual outcomes for participants (6, 7).

The psychosexual issues regarding the prospect of infertility in this population add to the overall experience of loss and mortality. To face death and at the same time to surrender one’s chance of living on in one’s offspring must present a depressing, noxious combination for many of the young, childless patients beginning treatment. On a marital level, the issue of possible infertility undoubtedly has a long-term negative effect on the stability of the relationship as well as the need to renegotiate aspects of the implicit relationship contract. Unattached patients may not worry about possible loss of fertility in the early stages of diagnoses and treatment but still may feel damaged and limited in their capacity as a potential mate. Efforts are being made to prevent or limit loss of fertility for some groups of patients. Further research in this area is urgently needed to alert the medical community to this issue and to develop strategies for helping these patients cope with this immense psychosocial stressor.

Although psychosocial causes are responsible for much of the sexual and procreative difficulty that survivors experience, physical causes are to some extent more easily researched and identified. Therefore, the vast majority of studies in this area focus on medically caused sexual and reproductive
dysfunction. In the following sections, this literature is reviewed by disease site and treatment modality.

Sexual and Reproductive Side Effects of Surgery

Breast Cancer

Breast cancer patients may be the best researched group in terms of the sexual impact of treatment on sexual functioning. Partly because radical mastectomy had been the treatment of choice for all breast cancer patients, the effects of breast loss on women’s sexual experience and life were researched early. In recent years, it has been widely accepted that comparable survival rates may be obtained in early breast cancer patients treated either with traditional surgical procedures (modified radical mastectomy) or with breast-conserving techniques combined with radiation and, increasingly, chemotherapy. The psychological and psychosexual outcomes of these two approaches have been compared in a number of studies. Although some studies report a tendency toward better preservation of body image and higher level of enjoyment of breast caressing in patients with breast preservation or reconstruction (8, 9, the groups do not show any differences in sexual frequency, ease of reaching orgasm and overall sexual satisfaction. It is also possible that age at the time of treatment plays a significant role in these patients’ perception of quality of life. Wenzel et al. (10) found that immediately after treatment for breast cancer, younger women (50 years and younger) reported significantly worse overall quality of life than the older women in their study. No significant differences in sexual dysfunction or body image were noted in this study.

In an effort to clarify the nature of women’s response to lumpectomy, McCormick et al. (11) studied 74 women following lumpectomy and radiation and reported that 39% of the sexually active patients avoided the treated breast, 20% stated that their partner avoided it, and 48% noted breast discomfort during sexual activity; still, 90% indicated a high level of satisfaction with the results of their treatment.

The implications of breast reconstruction for the psychological adjustment of the mastectomy population are also beginning to receive attention. Rowland et al. (12) studied 83 women who had undergone reconstruction after modified radical mastectomy for early stage breast cancer and reported that these patients generally returned to premorbid levels of sexual satisfaction and comfort. The timing of the reconstructive surgery may be a relevant factor for these women. In a retrospective study of women who had undergone immediate breast reconstruction after breast cancer surgery, and women who had delayed breast reconstruction, Al-Ghazal et al. (13) found significantly superior outcomes for women who had undergone breast reconstruction at the time of their initial surgery.

Although there is now a growing body of research dealing with the emotional and sexual consequences of surgery for early stage breast cancer, little is known about the effects of systemic regimens for breast cancer on sexual functioning. In a survey of 1098 women who had been diagnosed with breast cancer 1–5 years earlier and who had been treated with different adjuvant regimens, Ganz et al. (14) found that patients who had received chemotherapy seemed to experience a higher incidence of vaginal dryness and pain during intercourse, whereas women treated with tamoxifen reported a higher incidence of hot flashes, night sweats, and vaginal discharge. In another study of this population, Ganz (15) found that although rates of sexual activity did not decline, women taking tamoxifen reported slightly higher rates of difficulty with arousal and achieving orgasm. In a large survey of breast cancer survivors, Meyerowitz et al. (16) found no significant differences between their subjects and age-matched healthy women on a standard measure of sexuality. However, women who were most likely to have reported negative impact on their sexuality from cancer treatment included women who had experienced changes in their hormonal status.

A further concern is posed by the large number of women now receiving hormonal treatment, especially tamoxifen, for long periods. The long-term side effects of these treatments are only now emerging slowly and require more research in the future. Research to date suggests that tamoxifen actually may produce estrogenic changes in the vaginal mucosa of postmenopausal women (17, 18). However, its impact on symptomatic vaginal atrophy in these women is unknown (19).

Cancer of the Female Reproductive Organs

The incidence of sexual problems in women after gynecologic cancer treatment ranges in various reports from 0% to virtually 100% (20). This reflects both the many methodologic difficulties of assessment in this field and the varied treatments for gynecologic malignancies. These treatments range from laser surgery for cervical carcinoma in situ to total pelvic exenteration and vigorous chemotherapies for advanced gynecologic tumors. The gynecologic malignancies, with their obvious significance for sexual function, deserve comprehensive study to help women recover sexually as fully as possible. As Van de Wiel et al. (21) point out in their review of sexual function after cervical cancer treatment, many studies use frequency of intercourse as the sole indicator of the quality of sexual relations. This sheds little light on the true sexual status of the gynecologic cancer survivor. Further refinements in research instruments and methodology hopefully will benefit this population.

Cervical Cancer

Cervical cancer is the fourth most common neoplasm in women, with 13,000 new cases of invasive disease diagnosed annually in the United States. Excluding in situ lesions, treatment consists of radical hysterectomy, radiation therapy, or a combination of both approaches. Studies comparing sexual outcomes for radiation treatment and surgery indicate that at 6 months posttreatment, both surgery and radiation patients reported no significant changes in sexual functioning. At 1-year posttreatment, however, both populations reported decreased sexual interest and radiation patients reported significantly diminished sexual functioning with severe dyspareunia, postcoital bleeding, and pain on penetration. These studies highlight the difficulties posed for sexual recovery by pelvic irradiation for gynecologic cancer. The sequelae of fibrosis, vaginal stenosis, and decreased lubrication (22) are likely to interfere with sexual function unless treated appropriately, promptly, and continuously with vaginal dilators, effective vaginal lubricants (e.g., Astroglide and others) and, in some cases, a hormone-free vaginal moisturizer such as Replens.

Total pelvic exenteration is a surgical procedure occasionally performed to excise advanced pelvic tumors en bloc in the absence of distant metastases. The surgery entails removal of the bladder, urethra, vagina, uterus, ovaries, and rectum; two ostomies are created. The treatment is such a serious challenge to both physical and emotional recovery that early clinical reports explored whether postoperative quality of life justified the continued use of so radical an approach. Some researchers have reported that construction of a neovagina combined with special support and counseling efforts offers an improved chance for sexual rehabilitation after surgery (23).
At present, however, many questions remain regarding vaginal reconstruction. The long-term advantage to patient adjustment and satisfaction must be weighed against the risk of these procedures. The psychological and practical adjustments required by exenteration, which include body image, ostomy, and mortality concerns, also merit continued further study.

The impact of gynecologic cancer on a woman’s sexual self-esteem or sense of worth as a sexual partner remains an intuitively powerful yet little studied factor in postcancer distress. Van de Wiel et al. (21) compared 11 women treated for cervical carcinoma with a group of nonpatient controls and found that although the frequency of sexual activity did not differ between the groups, the patients with cervical cancer valued sexual interactions significantly less and had a lower self-appraisal of themselves as sexual partners. Although the small populations studied and the retrospective nature of the work limit conclusions, this report marks a valuable effort to illuminate the subtler but far-reaching consequences of gynecologic cancer for sexual well-being.

Endometrial and Ovarian Cancer

Endometrial cancer presents most commonly in postmenopausal women. Treatment consists of surgery, radiation therapy, chemotherapy, or a combination of modalities. Ovarian cancer presents in premenopausal and postmenopausal women; surgical evaluation and debulking are ordinarily the first step in treatment, followed by a chemotherapeutic regimen with a combination of agents. Only with the advent of chemotherapy for ovarian cancer has the previously dismal prognosis for this tumor improved markedly. Studies of the long-term implications of this illness for the survivor’s sexual function have begun to appear. Compared with healthy controls, women with these cancers report lower frequency of sexual behaviors, lower levels of arousal, increased incidence of dyspareunia, and problems with body image.

The ovarian cancer patient faces the serial trauma of a serious cancer diagnosis, major pelvic surgery with resultant changes to the vagina, a demanding chemotherapeutic regimen, treatment-related onset of menopause in the premenopausal patient, and complete loss of fertility. The psychological, physical, and hormonal impact on sexual function in this population merits further careful study.

The endometrial cancer patient must often contend with radiation changes to the vagina and pelvis. Vaginal changes include fibrosis with resultant shortening and narrowing; reduced elasticity of the vaginal wall; and diminished lubrication, creating high risk of dyspareunia. As mentioned earlier, the consequences of radiation to the vagina may be avoided or alleviated by the regular use of vaginal dilators and sexual comfort can be improved by the use of appropriate lubricants, vaginal moisturizers, and intercourse positions. An important area for future inquiry is the implementation of patient support and education plans for women facing pelvic radiation, which may increase contact with health care providers and encourage crucial patient compliance with these strategies during the demanding months of treatment, especially during the first year posttreatment, as radiation changes evolve and produce physical and relationship distress.

Vulvar Cancer

Vulvar carcinoma is a rare tumor arising primarily in older women. In early stage disease, treatment may consist of wide local excision (24). In more advanced disease, the lesions are often multicentric and radical vulvectomy is performed, which entails removal of clitoris, labia minora and majora, and bilateral inguinal lymph node dissection. Postoperatively, patients may experience a high degree of complications, including wound infections and lymphedema of the lower extremities as well as introital stricture. Research attention has begun to focus on this population in recent years (25) and reports document that sexual dysfunction posttreatment for vulvar cancer is common and affects all phases of the sexual response cycle.

Sexual and Reproductive Implications of Systemic Cancer Treatments in Women

Sexual and reproductive consequences of surgery are obvious, occur at the time of treatment, and are usually permanent. In contrast, the side effects of radiation and chemotherapy may accumulate over time and may not be permanent. Premature menopause, which is a frequent long-term side effect of systemic cancer treatments, such as chemotherapy, hormone therapy, and pelvic irradiation, has implications for both sexual and reproductive functioning. Ovarian failure secondary to single agent and combination chemotherapy has been documented (26). Alkylating agents appear to be the most notorious cause of ovarian failure in older women (aged 40 and older). Resulting symptoms include amenorrhea and menopausal symptoms, such as hot flashes, irritability, vaginal dryness, and atrophy of the vaginal epithelium. The treatment increases the likelihood of vaginitis, dyspareunia, and decreased sexual interest. Although some women recover normal ovarian functioning after treatment, premature menopause is the long-term outcome for many women. Aside from the specific drug regimen used, age is an important variable in this context, with older women more prone to loss of fertility and early menopause, particularly after treatment with larger, cumulative drug doses. In a study of women who received high-dose chemotherapy for breast cancer with autologous bone marrow support, Winer et al. (27) found that although overall quality of life after treatment was relatively high in this population one or more years after completion of treatment, problems with sexual functioning were common.

Gonadal dysfunction and infertility after radiation therapy are difficult to predict. The central location of the ovaries within the pelvis, close to major nodal areas, makes damage from radiation scatter and leakage likely. As with chemotherapy, radiation damage is dose-related, cumulative, and age-dependent. Loescher et al. (28) found that permanent infertility after 25 treatments of 500 Gy occurred in 60% of women aged 15–40 years and in 100% in women aged over 40. Because pelvic radiation interferes with the vasocongestive processes of female sexual arousal, vaginal lubrication also may be impaired, and dyspareunia and vaginitis may develop. Therefore, pelvic radiation may result in long-term adverse effects on female sexual functioning.

Radiation treatment is often combined with chemotherapeutic regimens. In such cases, it is difficult to differentiate between toxicity incurred from radiation versus that due to the chemotherapeutic agent(s). Data from women who received combined radiation and chemotherapy for Hodgkin disease suggest that these combination treatments result in additive ovarian toxicity (29).

Cancer of the Male Reproductive Organs

Prostate Cancer

Prostate cancer is the most commonly diagnosed cancer in men. It affects mostly older men: 80% of all diagnoses
are made in men aged 65 years and older. In recent years, partly due to improved screening and diagnostic methods, the proportion of younger men in the newly diagnosed population seems to increase. Older men and their partners in this age group are often at a developmental stage dominated by losses: retirement, death of peers, and separation from adult children who move away. These losses may include diminished sexual activity secondary to sexual dysfunction that precedes the cancer diagnosis. Changes in sexual functioning due to normal aging are often compounded by age-related chronic diseases and their treatments, such as hypertension and diabetes. Zinreich et al. (30) reported that 63% of 43 patients (mean age, 67.7 years) with varying stages of prostate cancer had erectile dysfunction before undergoing any cancer treatment. Of these, 44% were never able to obtain an erection and 56% reported difficulty maintaining erections during intercourse. For many elderly couples, the man’s erectile difficulty results in a complete cessation of sexual activity.

Treatment for early stage disease commonly consists of surgery or radiation therapy. In early stage prostate cancer, the advances in medical technology have meant gains for sexual functioning posttreatment. Quinlan et al. (31), in a case series of 500 men, reported an incidence of erectile dysfunction of 32% with nerve-sparing surgery techniques, compared with 85% after radical prostatectomy. Recovery of erectile functioning is often slow, however, and may exceed 6 months in some patients.

Traditional radiation regimens for prostate cancer may also produce erectile dysfunction as a long-term side effect. Schover (32) found in a review of the literature that the generally estimated 50% of erectile dysfunction after definitive radiotherapy may be inflated. The actual incidence may lie between 14% and 46% of all cases. The mechanism believed to be responsible for the development of erectile dysfunction in radiation patients is vascular scarring, which may develop 6 months posttreatment or later. Helgason et al. (33) confirmed the general observation of increased incidence of erectile dysfunction in men treated with radical prostatectomy, compared to men treated with external beam radiation.

Advanced-stage prostate cancer is commonly treated with testosterone deprivation, accomplished by bilateral orchiectomy or the administration of estrogen, flutamide, or luteinizing hormone-releasing hormone analogues. All these interventions produce sexual side effects, including loss of desire for sexual activity and impaired erectile functioning. Men undergoing hormone treatments are also confronted with body image issues, reduced energy levels, and hot flashes, which may contribute to the development of sexual problems.

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