Women's Sexual Function and Dysfunction. Irwin Goldstein MD

Cancer, sexuality and sexual expression

Michael L Krychman, Alison Amsterdam, Jeanne Carter

Introduction

Sexual concerns are common for patients during the diagnostic, treatment, and recovery phases of their cancer. As patients move away from the acute phase of illness, healthy sexual function is an important step toward re-establishing their sense of normalcy and well-being.1 Approximately one-half of women who survive a breast or gynecologic malignancy report severe and long-lasting sexual problems.2 Andersen3 noted that sexual function morbidity occurs in up to 90% of women who have been diagnosed with cancer. Others have reported posttreatment sexual dysfunction incidences of 30-100%.2,4 Most commonly, these patients report hypoactive desire disorder and/or dyspareunia (see Chapters 11.1-11.3 and 12.1-12.6 of this book).

Several physiologic and psychologic factors that are specific to oncology patients, such as radical surgical procedures, pelvic radiation, menopausal symptoms, premorbid sexual dysfunction, and negative self-concept, can increase sexual morbidity5,6 (see Chapters 7.1-7.4). In addition, body-image concerns present a psychologic barrier to intimacy and sexual desire (see Chapter 6.1). Partner conflicts and relationship miscommuni- cations can be severe and debilitating7 (see Chapters 3.1—3.4).

Technological advances have changed clinicians’ views of cancer; it is now often seen as chronic illness. The medical community continues to improve therapeutic modalities by focusing on techniques that not only improve cancer survival rates but also decrease long-lasting side effects. In many cases, cancer has come to resemble a chronic, rather than terminal, illness. Survivorship initiatives are now a critical focus of many cancer institutions and governmental organizations. Post-treatment resources as well as sexual health programs are integral parts of these survivorship initiatives.

Sexual function is identified by cancer survivors as a critical component of quality of life.8,9 Typically, sexual problems have an acute onset, appearing shortly after treatment ends or when sexual intercourse is resumed. Studies investigating the interaction between a woman’s sexual self-concept and her sexual function show that women with a negative sexual self-concept are more likely to have greater sexual morbidity.8 Many patients report that sadness and grief emerge during sexual experiences, leaving them vulnerable to sexual dysfunction and a sense of sexual inadequacy.1 Sexual dysfunction may threaten the integrity of relationships, limiting this source of social support at a time when it is most needed.1,7,10 With a healthy sexual life, interpersonal relationships can be more intimate, romance can be more meaningful, and life can be approached with greater enthusiasm.11

Breast cancer

Treatment of breast cancer and sexual concerns

Introduction

Breast cancer is the most common malignancy in women (see Chapter 7.4).12 In 2004, there were an estimated 215 990 new cases of female breast cancer, and approximately 40 110 women died from this disease.13 Twenty-five percent of new cases present before menopause, and 15% present before the age of 45.14-16 Women who receive a diagnosis of breast cancer often receive combination therapy with surgical excision, followed by chemotherapy,17,18 radiation therapy, and/or hormonal manipulation. The duration, dosage, and type of therapy, along with the patient’s age, are strong determinants of whether or not the patient will undergo premature ovarian failure and enter menopause.19,20 The constellation of menopausal symptoms (hot flashes, sleep disturbances, vaginal atrophy, and mood alterations) can affect the sexual response cycle and have a major impact on patients’ sexual function.

Surgery

Operative procedures can change structural anatomy and compromise the neurovascular integrity of organ systems critical to sexual responsiveness. The surgical removal of organs or tissues can also affect self-image and self-esteem. Several scientific reviews examined the impact of breast surgery on sexual function and concluded that conservative operative procedures and/or reconstruction played only minor roles in sexual function.21,22 Patients who have undergone breast conservation surgery may be more likely to engage in breast caressing than women who have undergone mastectomy. However, the two groups do not differ with respect to coital frequency, ease of orgasm, or overall sexual satisfaction. Women who have undergone total mastectomy often have issues relating to altered body image and may develop a negative sexual self-schema. Some women complain of decreased breast stroking, while others may enjoy heightened erotic sensations when having their surgical incision caressed. Those who suffer from lymphedema, which can be painful and discomforting, complain of arm pain, paresthesia, skin sensitivity, swelling, and stiffness. These symptoms can limit mobility and affect sexual positioning. Compression garments, which are often used as standard therapy, may influence activities of daily living, such as sporting activity choices or wardrobe selection.

The BRCA1 and BRCA2 genes belong to a class of genes known as tumor suppressor genes. Like many other tumor suppressor genes, BRCA1 and BRCA2 regulate the cycle of cell division by keeping cells from growing. In particular, BRCA1 and BRCA2 inhibit the growth of cells that line the milk ducts in the breast. Up to 10% of women with breast cancer may have a genetic predisposition. The majority of these (55-70%) are caused by mutations in either BRCA1 or BRCA2 and are associated with an increased risk of ovarian cancer.23 Some women may choose to undergo a risk-reducing bilateral salpingo- oophorectomy if they are found to be at increased risk of developing ovarian cancer. In a recent study by van Oostrom et al.,24 women who underwent a risk-reducing bilateral salpingo- oophorectomy were negatively affected with respect to sexuality and body image. In addition to surgically induced menopausal symptoms, they may also develop the other symptoms mentioned previously.

As well as risk-reducing bilateral salpingo-oophorectomy, many women may choose to undergo prophylactic mastectomy on the breast unaffected by breast cancer. Fear of bilaterality or another primary breast cancer may influence women to proceed with this surgical intervention. Some women opt for reconstruction while others do not. The issues surrounding reconstruction, satisfaction with cosmetic result, and the impact on sexual function should not be underestimated.

Radiation

Radiation therapy often causes skin damage and changes, fatigue, alopecia, diarrhea, nausea, and vomiting. Many radiation-induced symptoms contribute to general malaise and may affect the sexual response cycle, most commonly libido. In addition, patients and/or their partners sometimes believe the myth of being “radioactive”. Skin thickening and discoloration of the irradiated breast can affect self-esteem and sexual function. Moreover, scars and fibrosis of the skin of the breast and axillary region can limit range of motion and contribute to lymphedema.

Chemotherapy

Many chemotherapeutic agents cause nausea, diarrhea, mucous membrane irritation, hot flashes, and vaginal atrophy. Hair loss on the head, eyebrows, eyelashes, and genitals is also common and may lead to changes in self-esteem and sexual attractiveness.

Premature ovarian failure can result from treatment with radiation and chemotherapy. The probability that a woman will enter menopause as a result of chemotherapy increases dramatically at the age of 35. More than 40% of women receiving chemotherapy at the age of 40 may become amenorrheic from treatment.25 This may lead to menopausal symptoms, such as dyspareunia, vaginal atrophy, and hot flashes. This syndrome has been attributed to alterations in estrogen and/or androgen hormone levels. The vaginal lining may become thin and lose its pliability and elasticity, leading to pain with coital penetration. Patients may also complain of hypoactive desire disorder when their levels of sexual interest had been adequate prior to the entering of menopause. Hot flashes can affect mood and can lead to sleep disturbances and irritability, and ultimately affect the sexual response cycle.

Since breast cancer is often hormonally sensitive and tumor cells possess estrogen and progesterone receptors, treatment of menopausal sequelae with systemic hormone therapy is contraindicated. The use of alternative medications, including selective serotonin reuptake inhibitors, antihypertensive medications, and environmental modifications (rhythmic breathing, acupuncture, avoiding spicy foods and alcohol, and dressing in layers) is becoming more widely accepted to help decrease the intensity and severity of menopausal symptoms.

The potential for ovarian failure and cessation of menses can lead to a constellation of psychologic stressors surrounding the potential loss of reproductive capacity. One should not underestimate the impact that loss of reproductive capacity can have on a woman; the anxiety, stress, and mood changes can be severe when the survivor recognizes that she will no longer be able to bear children.

Hormonal therapy

Selective estrogen receptor modulators and aromatase inhibitors can exacerbate menopausal symptoms (see Chapters 5.5 and 6.1-6.3). Tamoxifen is a selective estrogen receptor modulator prescribed to block estrogen receptors in the breast, but it also acts as a weak estrogen agonist on the uterine lining. It has been linked to reports of vaginal dryness, excessive vaginal discharge, vaginal soreness, delayed orgasm, and changes in libido.26 Studies that have looked at the impact of tamoxifen on sexual function have proven inconclusive.22,27,28

According to the Breast Cancer Prevention Trial, only minor differences in sexual function were seen in women taking tamoxifen versus those not on the drug. In contrast, Mortimer et al.29 noted no alteration in desire, arousal, or orgasm in patients on tamoxifen. However, more than 50% complained of vaginal discomfort and dyspareunia in spite of continued vaginal lubricant use. This was supported by Day et al.,30 who reported that women on tamoxifen had increased vaginal discharge with associated genital pruritus.

Aromatase inhibitors are also used in women with various stages of breast cancer. In the pathway of steroidogenesis, the aromatase inhibitors halt the conversion of testosterone to estrogen, thus lowering levels of circulating estrogens. Although this is often a desired oncologic result, it may exacerbate menopausal sequelae and bone loss. There are limited data available that specifically address the impact of this class of drugs on sexuality and other parameters of quality of life.

Psychologic concerns

The psychologic adjustment of female survivors of breast cancer has been extensively studied (see Chapters 3.1—3.4). The literature shows that many women adapt well after they learn of their diagnosis. However, a subset of women report continued anxiety, depressive symptoms, distress concerning body image, fear of recurrence, post-traumatic stress disorder, and sexual problems even after they are treated and deemed free of disease.25

Sometimes, prior negative sexual experiences may be inappropriately linked to cancer and/or its recurrence. Past sexual behavior (involving promiscuity, extramarital affairs, and sexually transmitted diseases) may be erroneously attributed to the cancer diagnosis. Depression, changes in body image, and stress can contribute to female sexual difficulty.

Weight gain with chemotherapy and hormonal manipulation may also be an important determinant, and it has been linked to women’s feelings of attractiveness.31 Goodwin et al.32 noted a mean overall weight gain of 1.6 kg, with an average gain of 2.5 kg, in newly diagnosed breast cancer patients receiving chemotherapy, and a 1.3-kg gain in those taking tamoxifen. This increase in weight was not explained by increased caloric intake or decreased physical activity.

The dynamics of relationships can be strained and changed with a cancer diagnosis and therapy. Women may have to take time off from their roles as caregivers and/or wage earners. This affects their partners, who often have to assume more or different responsibilities. This modification of roles can create marital and financial tension for the couple. Worries regarding partner abandonment and sexual rejection can affect dating and hinder the development of intimate relationships. Single women who are breast cancer survivors may also face unique stressors, such as negotiating new relationships while deciding when to disclose sensitive medical information regarding medical illnesses, fertilities issues, and longevity. Other forms of distress include fear of recurrence, early death, and disfigurement, as well as financial, employment and insurance concerns.

Gynecologic cancer and sexuality

Gynecologic cancer accounts for 13.4% of all cancers affecting women33 (see Chapters 7.1—7.4). Tumors of the female reproductive tract include cancers of the vulva, vagina, cervix, uterus, fallopian tubes, and ovaries. Ten percent of cancer deaths in women can be attributed to gynecologic malignancy, with the largest proportion attributable to ovarian cancer. The side effects of treatment for gynecologic cancer may include hormonal disruption, reproductive failure, sexual morbidity, and bowel and bladder changes, in addition to the potential emotional and relationship alterations.1,34-36

The reproductive organs, the vagina, and the vulvar areas are obviously pivotal to female identity. Problems with these tissues and their function can adversely affect sexual interest and response. A woman’s sense of her own reproductive status, regardless of her actual childbearing history, is central to her identity as well. Ovarian failure secondary to treatment signifies both reproductive loss and the advent of menopause, a state with its own profound significance, including a host of symptoms.37

A woman receiving treatment for gynecologic cancer may undergo multiple treatment modalities, often delivered sequen- tially.1 Bowel resections and anterior/posterior exenterations for advanced gynecologic malignancy can result in stomas, colostomies, and ileoconduits for the patient. All these can affect self-image, and all have the potential of negative impact on the sexual response cycle. Many cancer institutes often have designated ostomy nurses who can help educate patients who have stomas or other medical appliances on proper hygiene and can provide useful techniques so that these devices do not hinder sexual activity.

Cancer treatment can negatively affect female fertility in several ways - by surgical removal of all or part of the reproductive organs; through chemotherapy with alkylating drugs, which can be toxic to the ovary; and/or by radiation therapy, which can cause sterility (permanent ovarian failure) by high doses to the ovaries.34

The trend over the past decade has been to provide adequate cancer treatment while also attempting to reduce long-term negative consequences.38 One technique that has gained recognition in the field of gynecologic oncology is the fertility-preserving treatment of radical vaginal trachelectomy, with laparoscopic pelvic lymphadenectomy for treatment of early-stage cervical cancers.39-44 The overall recurrence rate for women who have undergone laparoscopic vaginal radical trach- electomy is estimated to be 3%, which is not significantly different from radical hysterectomy.

With the prospect of radical surgery, a discussion regarding sexuality is often considered a low priority. However, sexual dysfunction is more than likely to occur, and adequate preparation may facilitate adjustment.45 After radical surgery, women experience changes in body image, self-esteem, and feminine identity.4^50 Significant loss in sexuality after pelvic exenteration has been reported in several studies.45,49-52 Many women report no sexual interest or ability to achieve sexual satisfaction due to the loss of sexually responsive tissue.47,51-53

The correlation between radiation therapy and sexual dysfunction is documented in the literature.54-56 Women experience problems with vaginal stenosis, loss of lubrication, and pain due to scarring after pelvic and vaginal radiation treat- ment.56 Direct intense vaginal radiation can cause severe fibrosis, loss of elasticity, and decreased pliability of vaginal tissues and vaginal inflammation. It is not uncommon for women to be apprehensive about sexual activity for fear of bleeding and pain, symptoms that may be associated with initial diagnosis and may elicit concerns about recurrence.57

Chemotherapy can also negatively affect sexual function. As with breast cancer patients, pre- and perimenopausal women receiving chemotherapy may abruptly experience menopausal symptoms resulting from estrogen deficiency. These symptoms can contribute to sexual difficulties and quality-of-life impair-ments.58

Sexual rehabilitation and treatment

Sexual assessment and/or counseling are seldom provided in the oncology setting. There are a number of different reasons for this - time constraints and the need to prioritize critical and complex treatment issues, practitioner discomfort in initiating a conversation regarding sexual function, and patient discomfort or embarrassment with this subject.9 However, a study exploring sexual function after gynecologic cancer treatment found that 78% of the women wanted to have a discussion about sexual matters but did not ask questions due to fear of rejection or inappropriate setting.59 Questions that are important to keep in mind when assessing sexual difficulties include information about a woman’s precancer sexual function, as well as her current sexual function. This will help to determine the degree of dysfunction experienced by the cancer patient. It is also very important to pay attention to a patient’s relationship with her partner.60

The assessment of the cancer patient includes a detailed history, physical examination, psychologic examination, and, when appropriate, laboratory or radiologic evaluation. Sexual status, orientation, and past sexual experience are also assessed. Patients are encouraged to see both the gynecologist and psychologist for initial evaluations and follow-up surveillance. The Memorial Sloan-Kettering Cancer Center has established a comprehensive multidisciplinary program to help female cancer patients cope with sexual difficulties that may be experienced during or after cancer diagnosis and treatment. The model focuses on both the psychosexual and physical aspects of sexuality by providing an evaluation that includes both a medical examination by a gynecologist and a psychosexual evaluation by a psychologist.

Once the comprehensive evaluation is completed, a therapeutic management scheme is formulated. Several of the following issues should be addressed.

Treatment of systemic illness(es)

Cancer patients often have other underlying medical issues that can affect sexual health. A detailed history and physical examination can identify medical concerns that may been neglected in the midst of cancer therapy. Evaluation and treatment of chronic illnesses, such as undiagnosed anemia, uncontrolled hypertension, hypercholesterolemia, and/or underlying thyroid dysfunction, can identify a factor that may affect sexual function. Treatment of chronic illnesses can also improve general well-being, thus facilitating improved sexuality.

Identification of medications

Often cancer patients are on multiple medications. Some of them may directly affect the sexual response cycle and cause sexual dysfunction. Antidepressants and antihypertensive medications can alter sexual desire, arousal, and orgasm. Physicians and nurses should check pharmacologic guides to identify potential offending agents. If possible, specific antidotes to sexual side effects of these treatments, such as oral selective phosphodiesterase type 5 inhibitors,61 can be prescribed alongside antidepressants and antihypertensives.

Behavioral modification

Patients with a cancer history are encouraged to make lifestyle modifications that improve quality of life. Well-balanced nutrition, active exercise regimes, discontinuing tobacco use, and minimizing alcohol consumption should be encouraged. Similarly, patients with sexual dysfunction are often given specific structured sexual tasks to help with specific sexual complaints. Examples include sensate focusing, guided imagery, relaxation techniques, and the exploration of sexual fantasies (see Chapters 11.1-11.5). Radiation-induced fatigue can be problematic for many patients, and many are encouraged to take frequent naps and plan sexual intimacy when well rested and fatigue is minimal. Alternate forms of sexual expression, such as erotic fantasy, mutual massage, intimate fondling and caressing, or manual, digital, or oral stimulation may be introduced. Patients and their partners may be encouraged to engage in alternative sexual positions. The missionary position may be the most uncomfortable sexual position for those with foreshortened vaginas. The side-to-side or female superior position may help limit deep pelvic thrusting to minimize vaginal discomfort during penetration.

Pain management

Chronic pain can influence a woman’s sexual response and limit her interest in sexual activity (see Chapters 12.1-12.6). When pain and fatigue are minimal, sexual expression should be encouraged. Techniques, such as warm soaks and physical therapy, to help loosen and strengthen tense muscles should be encouraged. Guided imagery, meditation, deep-muscle relaxation, and avoidance of lethargy are options that can also be explored. Pain- management specialists should be consulted to adjust or reduce opioid regimens, add adjunctive analgesics, and modify dosing schedules to decrease fatigue and lethargy while maintaining adequate pain relief.

Education

Patients should be educated about their genital anatomy and on how a cancer diagnosis and therapeutic procedures can affect their sexual function. The debunking of many long-standing sexual myths and instruction by trained professionals are also an important part of the educational process (see Chapters 18.1 and 18.2). Take-home items, such as pamphlets, books, digital videodisks, videos, and other visual aids, can provide reinforcement and future reference. The American Cancer Society’s booklet entitled Cancer and Sexuality is an excellent patient reference guide.

Psychotherapy

Certified sexual therapists are trained to deal with patients with cancer and with their associated body-image issues and changes in intimacy, sexuality, self-esteem, and mood. Sexual health patients are offered marital, individual, couples, and group therapy by trained therapists who deal with both oncologic and sexually based issues.

In general, most patients can benefit from brief psychosexual interventions, including education, counseling/support, and symptom management. Robinson2 conducted an intervention to increase compliance with vaginal dilation recommendations - a recognized method of maintaining vaginal health and good sexual function after radiation therapy. The intervention consisted of a psychoeducational group providing information and support regarding effective use of dilators and lubricants. The women attending the intervention were significantly more likely to follow recommendations for vaginal dilation than the control group.2 Local and national organizations relating to cancer support, sexual education, and fertility may also be useful references.

Pharmacologic intervention

Concerns regarding hormonal manipulation are common in breast and gynecologic cancer patients. Lifestyle changes (avoidance of spicy food, decreasing intake of caffeine and alcohol, and lowering the thermostat) and nonhormonal medications (selective serotonin reuptake inhibitors, clonidine patch, and megestrol acetate) can be used to help reduce systemic hot flashes when systemic estrogen is contraindicated or declined by patients. Patients with estrogen-sensitive tumors rarely agree to hormone therapy, probably due to the perception of an increased cancer risk associated with hormone therapy and/or the side-effect profiles. On the other hand, some patients may choose the systemic hormones estrogen and progesterone; these can be prescribed for menopausal symptom managements for short durations (see Chapters 13.1-13.3).

Local use of nonmedicated, nonhormonal vaginal moisturizers, or vitamin E suppositories, can provide alternative relief for the symptoms of vaginal atrophy. It is recommended that these agents be used two or three times weekly. Nonmedicated, nonhormonal vaginal moisturizers and estrogen were compared in a randomized, control trial that demonstrated that nonmed- icated, nonhormonal vaginal moisturizers improved vaginal cytology.62 Patients are instructed to wear a light pad when using vitamin E suppositories, because it may stain undergarments. The use of water-based vaginal lubricants with intercourse is also encouraged. However, lubricants and moisturizers that contain microbicides, perfumes, coloration, and flavors should be discouraged because these additives may irritate the vaginal mucosa. Patients and oncologists more often use local estrogen for the treatment of vaginal atrophy. Many clinicians have chosen to use a 17-P-estradiol tablet, which is minimally absorbed into the systemic circulation.63 Patients report that the tablets are also easy to use, less messy than cream preparations, and technically easier to insert than estrogen rings.64 Studies are currently under way at several institutions to further investigate the safety of this agent in the breast cancer population. Other topical preparations include vaginal creams, rings, gels, and lotions.

The safety of androgen therapy in the breast cancer population has not been adequately studied. There is concern that the testosterone can be aromatized to estrogen, which may reactivate or promote further tumor growth. Many breast cancer cells have androgen receptors. The experimental testosterone transdermal matrix patch has proven to be effective for libido issues; however, further randomized, controlled trials and safety data are warranted before consideration in this patient population.

Sexual devices

For patients who have undergone pelvic surgery or radiation therapy, vaginal shortening, vaginal narrowing, and scar tissue can often impede penetration, causing dyspareunia. Vaginal dilators with water- or hormone-based lubricants can help lengthen and widen the vagina and loosen the scar tissue that contributes to the pain and discomfort associated with vaginal intercourse. Supportive behavioral therapy is instrumental for continued compliance. The prescribed regimen for dilator use is often individualized; some benefit from short (5 min) daily use, while others use dilators three times a week for 15 min per usage. Dilators should be cleansed with gentle soap and water, rinsed completely, and stored in a cool location between uses. Devices, such as the EROS clitoral stimulator, can be prescribed for patients who have had cervical cancer or other pelvic cancers, such as rectal and vaginal cancers. Preliminary data presented by Schroder et al.65 at the 2003 annual conference of the International Society for the Study of Women’s Sexual Health show promise that this device may be helpful in combating arousal difficulty after cervical cancer therapy.

Sexually active survivors should always be informed about sexually transmitted disease prevention, and condom use should always be encouraged.

Alternative and complementary medicine

Many nonmedical pharmacologic therapies have worrying and potentially detrimental side effects without scientific evidence of their benefit in alleviating sexual dysfunction. Although patients try agents such as chocolate, ginseng, oysters, and black cohosh to enhance sexuality, randomized, controlled clinical trials are needed to ensure patient safety and efficacy, and to demonstrate a low side-effect profile.

Consultation

Referral for an evaluation by a subspecialist may be appropriate for certain clinical conditions. Such consultants may include oncologists, social services providers, nutritionists, exercise therapists, and psychiatrists. A list of clinicians and ancillary staff who are sensitive to sexual issues should be readily available for patients who take part in sexual health programs.

In addition, pain and palliative care providers need to reassure patients and their partners that even at the end of life, when intercourse may not be feasible, intimacy and emotional closeness should be encouraged.

Conclusions

Quality-of-life concerns in survivorship are at the forefront of importance for both clinicians and patients. Sexual concerns and dysfunctions, during or after cancer therapy, are often overlooked. The diagnosis and treatment of malignancy are very complicated and stressful. Physical changes and psychologic issues are complex in a cancer patient suffering from sexual complaints. The goal of a comprehensive sexual health evaluation and the resulting therapy is to promote sexual health by fostering open communication, providing anticipatory guidance, and validating normalcy with respect to sexual thoughts and feelings. Individual treatment plans are created and implemented by the sexual health-care professional team to educate patients and survivors so they can enjoy fulfilling and pleasurable sexual repertoires with their partners during and after cancer therapy.

References

1. Schover LR. Sexuality and Fertility After Cancer. New York: Wiley, 1997.

2. Robinson JW. Sexuality and cancer. Breaking the silence. Aust Fam Physician 1998; 27(1-2): 45-7.

3. Andersen BL. How cancer affects sexual functioning. Oncology (Huntingt) 1990; 4: 81-8; discussion, 92-4.

4. Andersen BL, Woods XA, Copeland LJ. Sexual self-schema and sexual morbidity among gynecologic cancer survivors. J Consult Clin Psychol 1997; 65: 221-9.

5. Devita VT, Rosenberg SA, Hellman S, eds. Cancer: Principles and Practices of Oncology, 6th edn. Philadelphia: Lippincott Williams & Wilkins, 2000: 3032-49.

6. Andersen BL. Surviving cancer: the importance of sexual selfconcept. MedPe^,atrOncol 1999; 33: 15-23.

7. Van de Wiel HB, Weijmer MC, Wouda EJ et al. Sexual functioning of partners of gynecologic oncology patients. Sex Marital Ther

8. Andersen BL, Cyranowski JM. Women’s sexuality: behaviors, responses, and individual differences. J£onsultÇlinPsyçhçl 1995; 63: 891-906.

9. Schover LR. Counseling cancer patients about changes in sexual function. Oncol (Huntingt) 1999; 13: 1585-92, 95-6.

10. Auchincloss SS. Sexual dysfunction in cancer patients: issues in evaluation and treatment. In JC Holland, JH Rowland, eds. Handbook of Psycho-Oncology, Psychological Care of the Patient with Cancer. New York: Oxford University Press, 1990: 383-413.

11. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999; 281: 537-44.

12. National Cancer Institute. PDQ treatment summary for health professionals. Cervical cancer. Bethesda: National Institutes of Health, 2002.

13. Jemal A, Tiwari RC, Murray Tetal. Cancer statistics, 2004. CA Cancer J Clin 2004; 54: 8-29.

14. Hankey BF, Miller B, Curtis R et al. Trends in breast cancer in younger women in contrast to older women. J Natl Cancer Inst Monogr 1994; 16: 7-14.

15. Higgins S, Haffty BG. Pregnancy and lactation after breast conservation therapy for early breast cancer. Cancer 1994; 73: 2175-80.

16. Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjunctive chemotherapy for breast cancer. J Clin Oncol 1996; 14: 1718-29.

17. Hortobagyi GN. Progress in systemic chemotherapy of primary breast cancer: an overview. J Natl Cancer Inst Monogr 2001; 30: 72-9.

18. National Institute of Health Consensus Development Panel. National Institutes of Health Consensus Development Conference Statement. Adjuvant therapy for breast cancer. 1-3 November 2000. J Natl Cancer Inst Monogr 2001; 30: 5-15.

19. Meirow D, Epstein M, Lewis H et al. Administration of cyclophosphamide at different stages of follicular maturation in mice; effects on reproductive performance and fetal malformations. Hum Reprod 2001; 16: 632-7.

20. Goodwin PJ, Ennis M, Pritchard KI et al. Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol 1999; 17: 2365-70.

21. Schover LR. Sexuality and body image in younger women with breast cancer. J Natl Cancer Inst Monogr 1994; 16: 177-82.

22. Schover LR, Yetman RJ, Tuason LJ et al. Partial mastectomy and breast reconstruction. A comparison of their effects on psychosocial adjustment, body image, and sexuality. Cancer 1995; 75: 54-64.

23. Offit K. Clinical Cancer Genetics. New York: Wiley-Liss, 1998.

24. van Oostrom I, Meiijers-Heijboer H, Lodder LN et al. Long-term psychological impact of carrying a BRCA1/2 mutation and prophylactic surgery: a 5-year follow-up study. J Clin Oncol 2003;

25. Kornblith AB, Ligibel J. Psychosocial and sexual functioning of survivors of breast cancer. Semin Oncol 2003; 30: 799-813.

26. Kaplan HS. A neglected issue: the sexual side effects of current treatments for breast cancer. J Sex Marital Ther 1992; 18: 3-19.

27. Ganz PA, Rowland JH, Desmond K et al. Life after breast cancer: understanding women’s health related quality of life and sexual functioning. J Clin Oncol 1998; 16: 501-14.

28. Meyerowitz BE, Desmond KA, Rowland JH et al. Sexuality following breast cancer. J Sex Marital Ther 1999; 25: 237-50.

29. Mortimer JE, Boucher L, Baty Jetal. Effect of tamoxifen on sexual function in patients with breast cancer. J Clin Oncol 1999; 17: 1488-92.

30. Day R, Ganz PA, Costantino JP et al. Health-related quality of life and tamoxifen on breast cancer prevention. A report from the National Surgical Adjuvant Breast and Bowel Project P-1. J Clin Oncol 1999; 17: 2659-69.

31. Demark-Wahnefried W, Rimer BK, Winer EP. Weight gain in women diagnosed with breast cancer. J Am Diet Assoc 1997; 97: 519-26, 29.

32. Goodwin PJ, Ennis M, Pritchard KI et al. Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis. J Clin Oncol 1999; 17: 120-9.

33. Fields AL, Jones JG, Thomas GM et al. Gynecologic cancer. In RE Lenhard, RT Osteen, T Gansler, eds. American Cancer Society’s Clinical Oncology. Altanta: The Society, 2001: 455-96.

34. American Cancer Society. Cancer Facts and Figures. Atlanta. Available at www.cancer.org.

35. Auchincloss S, McCartney C. Gynecologic cancer. In J Holland, ed. Psych-Oncology. New York: Oxford University Press, 1998: 359-70.

36. Byrne J. Infertility and premature menopause in childhood cancer survivors. Med Pediatr Oncol 1999; 33: 24-8.

37. Lagana L, McGarvey EL, Classen  C et al. Psychosexual dysfunction among gynecologic cancer survivors. J Clin Psych Med Setting 2001; 8: 73-83.

38. Plante M, Roy M. Radical trachelectomy. Oper Tech Gynecol Surg 1997; 2: 187-99.

39. Dargent D, Brun JL, Roy M et al. Pregnancies following radical trachelectomy for invasive cervical cancer. Gynecol Oncol 1994; 52: 105.

40. Dargent D, Martin X, Sacchetoni Aetal. Laparoscopic vaginal radical trachelectomy: a treatment to preserve the fertility of cervical carcinoma patients. Cancer 2000; 88: 1877-82.

41. Dargent D. Using radical trachelectomy to preserve fertility in early invasive cervical cancer. Contemp Ob Gyn 2000; 5: 23-49.

42. Roy M, Plante M. Pregnancies after radical vaginal trachelectomy for early-stage cervical cancer. Am J Obstet Gynecol 1998; 179: 1491-6.

43. Covens A, Shaw P, Murphy Jetal. Is radical trachelectomy a safe alternative to a radical hysterectomy for patients with stage IA-B carcinoma of the cervix? Cancer 1999; 86: 2273-9.

44. Shepard JH, Mould T, Oram DH. Radical trachelectomy in early stage carcinoma of the cervix: outcome as judged by recurrence and fertility rates. Br J Obstet Gynaecol 2001; 108: 882-5.

45. Gleeson N, Baile W, Roberts WS et al. Surgical and psychosexual outcome following vaginal reconstruction with pelvic exenteration. Eur J Gynaecol Oncol 1994; 2: 89-95.

46. Andersen BL. Sexual functioning complications in women with gynecologic cancer. Cancer 1987; 60: 2123-8.

47. Andersen BL, Hacker NF. Psychosexual adjustment following pelvic exenteration. Obstet Gynecol 1983; 61: 331-8.

48. Corney RH, Crowther ME, Everett H et al. Psychosexual dysfunction in women with gynecologic cancer following radical pelvic surgery. Br J Obstet Gynaecol 1993; 100: 73-8.

49. Fisher SG. Psychosexual adjustment following total pelvic exenteration. Cancer Nurs 1979; 2: 219-25.

50. Sewell HH, Edwards DW. Pelvic genital cancer: body image and sexuality. Front Radiat Ther Oncol 1980; 14: 35-41.

51. Dempsey GM, Buchsbaum HJ, Morrison J. Psychosocial adjustment to pelvic exenteration. Gynecol Oncol 1975; 3: 325-34.

52. Vera MI. Quality of life following pelvic exenteration. Gynecol Oncol 1981; 12: 355-66.

53. Brown RS, Haddox V, Posada Aetal. Social and psychological adjustment following pelvic exenteration. Am J Obstet Gynecol 1972; 114: 162-71.

54. Andersen BL, Andersen B, deProsse C. Controlled prospective longitudinal study of women with cancer: sexual functioning outcomes. J Consult Clin Psychol 1989; 57: 683-91.

55. Schover LR, Fife M, Gershenson DM. Sexual dysfunction and treatment for early stage cervical cancer. Cancer 1989; 63: 204-12.

56. Bruner DW, Lanciano R, Keegan M et al. Vaginal stenosis and sexual dysfunction following intracavitary radiation for the treatment of cervical and endometrial carcinoma. Int J Radiat Oncol Biol Phys 1993; 27: 825-30.

57. Gamel C, Hengeveld M, Davis B. Informational needs about the effects of gynecologic cancer on sexuality: a review of the literature. J Clin Nurs 2000; 9: 678-88.

58. Ganz PA, Coscarelli A, Fred  C et al. Breast cancer survivors: psychosocial concerns and quality of life. Breast Cancer Res Treat 1996; 38: 183-99.

59. Lancaster J. Women’s experiences of gynecologic cancer treated with radiation. Curationis 1993; 16: 37-42.

60. Schultz WC, Van de Wiel HB. Sexuality, intimacy, and gynecologic cancer. J Sex Marital Ther 2003; 29(Suppl 1): 121-8.

61. Shen WW, Urosevich Z, Clayton DO. Sildenafil in the treatment of female sexual dysfunction induced by selective serotonin reuptake inhibitors. J Reprod Med 1999; 44: 535-42.

62. Nachtigall LE. Comparative study: Replens versus local estrogen in menopausal women. Fertil Steril 1994; 61: 178-80.

63. Vagifem [package insert]. Denmark: Novo Nordisk A/S, 2003.

64. Rioux JE, Devlin MC, Gelfand MM et al. 17 beta estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause 2000; 7: 156-61.

65. Schroder M, Mell LK, Waggoner Setal. A clinical trial of EROS therapy for treatment of sexual dysfunction in irradiated cervical cancer patients. In International Society for the Study of Women’s Sexual Health, 16-19 October 2003, The Netherlands. Abstract (Poster no. 15).