Table of Contents Purpose of This PDQ Summary The Prevalence and Types of Sexual Dysfunction in People With Cancer Factors Affecting Sexual Function in People With Cancer
Assessment of Sexual Function in People With Cancer Pharmacological Effects of Supportive Care Medications on Sexual Function Treatment of Sexual Problems in People With Cancer Fertility Issues Get More Information From NCI Changes to This Summary (08/20/2008) Questions or Comments About This Summary More Information
Purpose of This PDQ Summary
This PDQ cancer information summary provides comprehensive, peer-reviewed information for health professionals about sexuality and reproductive issues that cancer patients may experience during or after treatment. This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board 1.
Information about the following is included in this summary:
- Treatment-related factors.
- Assessment.
- Treatment.
- Fertility issues.
This summary is intended as a resource to inform and assist clinicians and other health professionals who care for cancer patients during and after cancer treatment. It does not provide formal guidelines or recommendations for making health care decisions. Information in this summary should not be used as a basis for reimbursement determinations.
This summary is also available in a patient version 2, which is written in less technical language, and in Spanish 3. The Prevalence and Types of Sexual Dysfunction in People With Cancer
Sexuality is a complex, multidimensional phenomenon that incorporates biologic,
psychologic, interpersonal, and behavioral dimensions. It is important to
recognize that a wide range of normal sexual functioning exists. Ultimately,
sexuality is defined by each patient and his/her partner within a context of
factors such as gender, age, personal attitudes, and religious and cultural
values.
Many types of cancer and cancer therapies are frequently associated with sexual
dysfunction. Across sites, estimates of sexual dysfunction after various
cancer treatments have ranged from 40% to 100% posttreatment.[1] Research
suggests that about 50% of women who have had breast cancer experience
long-term sexual dysfunction,[2,3] as do a similar proportion of women who
have had gynecologic cancer.[4] For men with prostate cancer, erectile dysfunction (erections inadequate for intercourse) has been the primary form of sexual dysfunction investigated. Prevalence rates of erectile dysfunction have varied. In general, those studies that have used patients’ self-reports have found higher rates of erectile dysfunction ranging from 60% to 90% after radical prostatectomy and between 67% and 85% following external-beam radiation therapy.[5-8] Erectile dysfunction appears to be least prevalent with brachytherapy and most prevalent when cryotherapy is used to treat localized prostate cancer.[9] For Hodgkin lymphoma
and testicular cancer, 25% of people who have had these cancers are left with
long-term sexual problems.[3,10] Several articles summarize the literature on
sexuality and cancer, with a particular emphasis on cancer sites that have a
direct impact on sexual functioning.[11-13]
An individual’s sexual response can be affected in a number of ways, and the
causes of sexual dysfunction are often both physiological and psychological.
The most common sexual problems for people with cancer are loss of desire for
sexual activity in men and women, erectile dysfunction in men, and dyspareunia (pain with intercourse) in
women.[3] Men may also experience anejaculation (absence of ejaculation),
retrograde ejaculation (ejaculation going backward to the bladder), or the
inability to reach orgasm. Women may experience changes in genital sensations
due to pain or a loss of sensation and numbness, as well as a decreased ability
to reach orgasm. Loss of sensation can be as distressing as painful sensation
for some individuals.[14] In women, premature ovarian failure as a result
of chemotherapy or pelvic radiation therapy is a frequent antecedent to sexual
dysfunction, particularly when hormone replacement is contraindicated because
the malignancy is hormonally sensitive.[2] Most often, orgasm remains intact
for men and women, though it may be delayed secondary to medications and/or
anxiety.
Unlike many other physiological side effects of cancer treatment, sexual
problems do not tend to resolve within the first year or two of disease-free
survival;[2,7,15-19] rather, they may remain constant and fairly severe.
Although it is unclear how much sexual problems influence a survivor’s
rating of overall health-related quality of life, these problems are clearly
bothersome to many patients and interfere with a return to normal
posttreatment life. In a qualitative study of 48 men (130 approached) with erectile dysfunction after
treatment for prostate cancer, quality of life was significantly affected,
including areas such as the quality of sexual intimacy, everyday interactions
with women, sexual fantasy life, and perceptions of their masculinity. Patients who participated in a randomized trial that compared radical prostatectomy with watchful waiting were asked to complete a questionnaire regarding symptoms, psychological functioning, and quality of life. Although the frequency of sexual thoughts was similar in both groups, the prevalence of erectile dysfunction (changes in voluntary erection in sexual situations, erection on awakening, and spontaneous erections) was higher in the radical prostatectomy group (80%) than in the watchful-waiting group (45%). Among men who underwent radical prostatectomy, 56% were moderately or greatly distressed by the decline in sexual function, as compared with 40% of men in the watchful-waiting group.[20,21]
Assessment, referral, intervention, and follow-up are important for maximizing
quality of life and survival.[2,17]
References
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Derogatis LR, Kourlesis SM: An approach to evaluation of sexual problems in the cancer patient. CA Cancer J Clin 31 (1): 46-50, 1981 Jan-Feb.
[PUBMED Abstract]
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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 16 (2): 501-14, 1998.
[PUBMED Abstract]
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Schover LR, Montague DK, Lakin MM: Sexual problems. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1997, pp 2857-2872.
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Andersen BL: Quality of life for women with gynecologic cancer. Curr Opin Obstet Gynecol 7 (1): 69-76, 1995.
[PUBMED Abstract]
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Walsh PC, Epstein JI, Lowe FC: Potency following radical prostatectomy with wide unilateral excision of the neurovascular bundle. J Urol 138 (4): 823-7, 1987.
[PUBMED Abstract]
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Talcott JA, Rieker P, Clark JA, et al.: Patient-reported symptoms after primary therapy for early prostate cancer: results of a prospective cohort study. J Clin Oncol 16 (1): 275-83, 1998.
[PUBMED Abstract]
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Smith DS, Carvalhal GF, Schneider K, et al.: Quality-of-life outcomes for men with prostate carcinoma detected by screening. Cancer 88 (6): 1454-63, 2000.
[PUBMED Abstract]
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Stanford JL, Feng Z, Hamilton AS, et al.: Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the Prostate Cancer Outcomes Study. JAMA 283 (3): 354-60, 2000.
[PUBMED Abstract]
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Robinson JW, Moritz S, Fung T: Meta-analysis of rates of erectile function after treatment of localized prostate carcinoma. Int J Radiat Oncol Biol Phys 54 (4): 1063-8, 2002.
[PUBMED Abstract]
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Arai Y, Kawakita M, Okada Y, et al.: Sexuality and fertility in long-term survivors of testicular cancer. J Clin Oncol 15 (4): 1444-8, 1997.
[PUBMED Abstract]
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Auchincloss SS: Sexual dysfunction in cancer patients: issues in evaluation and treatment. In: Holland JC, Rowland JH, eds.: Handbook of Psychooncology: Psychological Care of the Patient With Cancer. New York, NY: Oxford University Press, 1989, pp 383-413.
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Lamb MA: Sexuality and Sexual Functioning. In: McCorkle R, Grant M, Frank-Stromborg M, et al., eds.: Cancer Nursing: A Comprehensive Textbook. 2nd ed. Philadelphia, Pa: WB Saunders Co, 1996, pp 1105-1127.
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Ofman US, Auchincloss SS: Sexual dysfunction in cancer patients. Curr Opin Oncol 4 (4): 605-13, 1992.
[PUBMED Abstract]
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Havenga K, Maas CP, DeRuiter MC, et al.: Avoiding long-term disturbance to bladder and sexual function in pelvic surgery, particularly with rectal cancer. Semin Surg Oncol 18 (3): 235-43, 2000 Apr-May.
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Fosså SD, Woehre H, Kurth KH, et al.: Influence of urological morbidity on quality of life in patients with prostate cancer. Eur Urol 31 (Suppl 3): 3-8, 1997.
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Helgason AR, Adolfsson J, Dickman P, et al.: Factors associated with waning sexual function among elderly men and prostate cancer patients. J Urol 158 (1): 155-9, 1997.
[PUBMED Abstract]
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Litwin MS, Hays RD, Fink A, et al.: Quality-of-life outcomes in men treated for localized prostate cancer. JAMA 273 (2): 129-35, 1995.
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Relander T, Cavallin-Ståhl E, Garwicz S, et al.: Gonadal and sexual function in men treated for childhood cancer. Med Pediatr Oncol 35 (1): 52-63, 2000.
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Broeckel JA, Thors CL, Jacobsen PB, et al.: Sexual functioning in long-term breast cancer survivors treated with adjuvant chemotherapy. Breast Cancer Res Treat 75 (3): 241-8, 2002.
[PUBMED Abstract]
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Steineck G, Helgesen F, Adolfsson J, et al.: Quality of life after radical prostatectomy or watchful waiting. N Engl J Med 347 (11): 790-6, 2002.
[PUBMED Abstract]
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Bokhour BG, Clark JA, Inui TS, et al.: Sexuality after treatment for early prostate cancer: exploring the meanings of "erectile dysfunction". J Gen Intern Med 16 (10): 649-55, 2001.
[PUBMED Abstract]
Factors Affecting Sexual Function in People With Cancer
Sexual dysfunction may be multifactorial; both physical and psychological
factors contribute to its development. Physical factors include functional
damage secondary to cancer therapies, fatigue, and pain. In addition, cancer
therapy such as surgery, chemotherapy, radiation therapy, and bone marrow
transplantation may have a direct physiologic impact on sexual function.[1]
Medications used to treat pain, depression, and other symptoms may contribute to
sexual dysfunction. Psychological factors include misbeliefs about the origin
of the cancer, guilt related to these misbeliefs, coexisting depression,
changes in body image after surgery, and stresses to personal relationships
that occur secondary to cancer.[2,3] Increasing age is often believed to be associated with decreased sexual
desire and performance; however, in one study, elderly men reported that sex remains important to their quality of life, that
performance can be maintained into the 70s and 80s, and that altered sexual
function is distressing.[4]
Treatment-Related Factors Secondary to Surgery
A number of cancer treatments have a direct physiologic impact on sexual
function. As treatment success has improved for some sites, attempts have
been made to modify treatment to reduce sexual morbidity. Several predictors
of postoperative sexual functioning include patient’s age, premorbid sexual and
bladder functioning, tumor location, tumor size, and extent of surgical
resection.
Breast cancer
Sexual function after localized treatment for breast cancer has been the
subject of a good deal of research. Several reviews concur that breast
conservation or reconstruction have only a minor impact in preserving sexual
function compared with a mastectomy alone.[5,6] Women who have breast
conservation, in particular, are more likely to continue to enjoy breast
caressing, but groups typically do not differ on less subtle variables such as
the frequency of sex, ease of reaching orgasm, or overall sexual satisfaction. A cross-sectional survey of younger women (aged 50 years or younger) with breast cancer found in multivariate analyses that having a mastectomy was associated with greater problems in interest in sex; chemotherapy was associated with greater sexual dysfunction.[7] Other studies confirm that sexual quality of life is disrupted more among those receiving chemotherapy, those who have undergone total mastectomies, those whose cancers were detected at later stages, and those with more depressive symptoms near the time of diagnosis.[8] Adjuvant tamoxifen therapy increases the rate of hot flashes, night sweats, and vaginal discharge, and increases the risk of premature menopause in women older than 45 years by approximately 10%. Furthermore, though rates of sexual activity with a partner did not decline, women taking tamoxifen reported slightly increased rates of difficulty with sexual arousal and achieving orgasm.[9,10]
Few studies evaluate sexuality in women with breast cancer that recurs. One longitudinal study compared women who were recently diagnosed with recurrent cancer with matched patients who were disease free. The recurrence group had less frequent intercourse, although there were no differences in sexual or relationship satisfication. As noted in other studies of women with breast cancer, sexual changes were more common among younger patients.[11]
Colorectal cancer
Sexual and urinary dysfunctions are recognized complications of resection for
rectal cancer. The main cause of sexual dysfunction from surgical resection
appears to be injury to the autonomic nerves in the pelvis along the distal
aorta from blunt pelvic resection or undefined cutting. Incidence of
genitourinary dysfunction depends on the type of surgery performed (i.e., the
plane of dissection, the degree of preservation of the autonomic nerves, and
the extent of pelvic dissection).[12,13] Nerve injury can occur via direct injury,
by vascular damage to the vasa nervosa, or where the blood supply to the nerves
that enter laterally is disrupted with traction or devascularization.[14]
The neuroanatomy for sexual functioning requires an intact autonomic nervous
system, which includes an interaction between the parasympathetic and
sympathetic nervous systems. Erection (parasympathetic-mediated response) is
governed by impulses traveling along the nervi erigentes that arise from the
second, third, and fourth sacral nerves,[15] whereas ejaculation depends on
sympathetic control. The sympathetic fibers originate from the lower thoracic
and upper lumbar segments of the spinal cord. These fibers descend along the
aorta, forming the superior hypogastric plexus near the aortic bifurcation.
The plexus divides into two trunks, which enter the pelvis along its lateral
walls as the hypogastric nerves. The parasympathetic fibers to the pelvis
join the hypogastric nerves on each pelvic wall to form the pelvic plexuses.[15]
One study provided a more extensive review of the anatomy of the pelvic
autonomic nerves and the relation of these nerves to the mesorectal fascial
planes.[16] Damage to the hypogastric (sympathetic) nerves or sacral
splanchnic (parasympathetic) nerves, or both, during surgical resection are the
most likely cause of urinary and sexual dysfunction.[17] Pelvic plexus
preservation is necessary to maintain erectile functioning, and both
hypogastric nerve and pelvic plexus preservation are necessary to maintain
ejaculate function and orgasm.[18]
Prostate cancer
In men, there is controversy whether the newer nerve-sparing technique for
radical prostatectomy is more or less successful in preserving erectile
function than definitive radiation therapy for localized prostate cancer. A
1994 survey of practice patterns found that 95% of randomly-sampled urologists
considered surgery the treatment of choice for clinically localized prostate
cancer in men younger than 70 years.[19] As follow-up studies of large groups of men undergoing radical prostatectomy have accumulated, estimates of the number who recover functional erections (firm enough to allow penile-vaginal penetration on most occasions) range from 10% to 40%, with estimates of functional erections following external-beam radiation therapy ranging from 15% to 33%.[20-24] Retrospective cohort studies have provided evidence indicating superior potency results with bilateral nerve-sparing surgical techniques.[25,26] One research group suggested that much of the superiority of
nerve-sparing over standard surgical technique in preserving potency is an
artifact of selection bias.[27] The men selected to receive nerve-sparing
surgery are those with the best potential to recover adequate erections. A systematic literature review using MEDLINE and CANCERLIT from January 1997 to June 2003 concluded that patient selection and surgical technique are the major determinants of postoperative erectile function in patients receiving treatment for localized prostate cancer. For properly selected patients undergoing a nerve-sparing radical prostatectomy by an experienced surgeon, unassisted or medically assisted erections postoperatively should be achieved.[28]
Other studies suggest that three-dimensional conformational radiation therapy may be superior to radical prostatectomy in preserving erectile function.[21,29-34] Rates of potency are typically in
the 30% to 60% range, with conformal therapy superior to older
techniques.[21,35-37] Men who are older and in poor health, however, are often
directed into radiation therapy, so that researchers often report
posttreatment sexual function only for the subgroup that began with good
erections. Furthermore, long-term follow-up is needed in comparing surgery with
radiation therapy because recovery of erectile function typically occurs within
a year or so after radical prostatectomy, whereas the damaging impact of radiation
on erectile function is slow and gradual, with declines still being observed as
long as 2 or 3 years after treatment. A retrospective cohort study of men treated with either radical prostatectomy or external-beam radiation therapy (EBRT) revealed significantly greater prevalence of erectile dysfunction in the surgery group at 5 years after diagnosis (79.3% vs. 63.5%).[38] The mechanism of injury to erectile
function also differs between surgery and radiation therapy. Radical
prostatectomy damages nerves that direct blood flow into the penis, ultimately
decreasing oxygenation of these tissues and increasing collagen deposits that
interfere with the penile tissue relaxation essential for firm erection.[39]
Radiation therapy appears to damage the arterial system that transports blood
to the penis.[40] A retrospective review of population-based data suggests that the choice of primary treatment for prostate cancer is not associated with 2-year general health-related quality-of-life outcomes.[41]
Prostate brachytherapy with permanent radioactive implants is an increasingly popular choice for the treatment of prostate cancer. Two isotopes are commonly used: iodine 125 (125I) and palladium 103 (103Pd).[42] With brachytherapy, ejaculation is preserved and age (91% of men younger than 50 years) correlates with return of sexual function.[43] However, a decline in potency as a function of time following treatment is expected in patients treated with brachytherapy.[42] One study found an actuarial preservation of potency after brachytherapy alone of 79% at 3 years and 59% at 6 years.[44] Another study found lower rates, with 57% of men fully potent or with mild erectile dysfunction at baseline remaining so at 30 months postbrachytherapy.[45] Potency rates after brachytherapy are significantly influenced by the addition of EBRT and/or neoadjuvant hormonal deprivation. Patients who received brachytherapy alone had a 5-year potency rate of 76%, compared with a potency rate of 56% for those treated with brachytherapy and EBRT. Patients who received a combination of EBRT, neoadjuvant hormonal deprivation, and brachytherapy had a 5-year potency rate of 29%.[42]
The etiology of erectile dysfunction following brachytherapy is unknown; however, radiation damage to nerve bundles and vascular structures has been proposed as a cause.[42] One study investigated retrospectively the relationships between the dose of radiation to structures putatively involved in prostate brachytherapy–induced erectile dysfunction and incidence of postbrachytherapy erectile dysfunction. This study found no increased risk of erectile dysfunction with increasing dose to the crus or neurovascular bundle, proposing a possible dose-response relationship between the risk of erectile dysfunction and radiation dose to the bulb.[46]
Other pelvic tumors
Nerve-sparing approaches to surgery appear to enhance recovery of erections at
least to some degree after radical cystectomy [47,48] and colorectal surgery.[49,48] Although the sexual side effects of definitive radiation therapy for pelvic
malignancies other than prostate cancer have not been well researched, outcomes
similar to those after prostate cancer treatment would be expected when the
dosage and field affect the pelvic vascular bed.
Pelvic surgeries in women include hysterectomy/oophorectomy, cystectomy,
vulvectomy, and abdominoperineal resection and often involve removal of a
portion of the vagina or other parts of the female genital anatomy. Older studies indicated that few women reported dyspareunia or loss of orgasmic capacity after radical hysterectomy;[50,51] however, a newer prospective study of women with early-stage cervical carcinoma who had undergone radical hysterectomy compared with control women reported severe orgasmic problems and uncomfortable sexual intercourse due to reduced vaginal size during the first 6 months after surgery. Throughout the first 2 years after surgery, the women reported persistent lack of sexual interest and lubrication.[52] Radical cystectomy for bladder cancer is more often
associated with pain from reduced vaginal depth and caliber resulting from
resection of the entire anterior vaginal wall. These patients may resume
pain-free intercourse, normal sensation, and orgasm with the help of
counseling, hormone therapy, and use of vaginal dilators.[53] Conservation of
vaginal tissue may reduce some of these problems. Decreased morbidity has been
reported from sparing of vulvar tissue with a partial vulvectomy versus radical
vulvectomy, yet the amount of tissue resected has not been a good predictor of
postoperative sexual satisfaction.[54] Rather, it is the quality of a woman’s
relationship with her partner that correlates with sexual function.[55] Women
who undergo abdominoperineal resection may also report pain with intercourse
related to loss of cushioning from removal of the posterior vaginal wall. In
addition, pelvic adhesions or scarring may contribute to dyspareunia after an
anterior/posterior resection.
Radical resection of recurrent pelvic tumors in women (pelvic exenteration) involves partial or complete removal of the vagina and levator muscles. Vaginal reconstruction produces satisfactory function and aesthetic results in some patients.[56]
Treatment-Related Factors Secondary to Systemic Chemotherapy
Chemotherapy is associated with loss of desire and decreased frequency of
intercourse for both men and women. Common side effects experienced after
chemotherapy include nausea, vomiting, diarrhea, constipation, mucositis,
weight changes (gain or loss), and altered sense of taste and smell.[3] These
symptoms often leave individuals feeling asexual. Alopecia is often one of the
most distressing side effects with associated changes in body image.[57] Loss of
pubic hair can also be particularly uncomfortable, which, in turn, promotes
asexual feelings.
For women, cytotoxic agents are associated with vaginal dryness, dyspareunia,
reduced ability to reach orgasm, and for older women, greater risk of ovarian
cancer.[3,58-60] Premature ovarian failure secondary to chemotherapy or radiation
brings the sudden onset of menopausal symptoms, and women who experience sudden
loss of estrogen and androgen production from the ovaries experience a number
of associated sexual changes. Sexual symptoms associated with estrogen
deprivation include vaginal atrophy, thinning of the vulvar tissues and vagina,
loss of tissue elasticity, decreased vaginal lubrication, hot flashes,
increased frequency of urinary tract infections, mood swings, fatigue, and
irritability. In addition, for younger women with breast cancer, menopausal symptoms as a result of therapy contribute to poorer health perception and quality of life.[61] A study of the psychosocial aspects of the transitional period between the end of primary breast cancer treatment and survivorship enrolled 558 women. They were treated with surgery (either mastectomy or lumpectomy) with and without chemotherapy, and the health outcomes examined included physical, emotional, and sexual functioning, as well as mood and symptoms. Sexual functioning was worse for women who received chemotherapy, regardless of the type of prior surgery (i.e., mastectomy or lumpectomy). These problems with sexual function were likely related to problems with vaginal lubrication and a change in menopausal status, both of which are more common in those receiving chemotherapy.[62] Because of concerns over causing recurrence of breast cancer, hormone replacement therapy is often not recommended for women who have become menopausal during treatment.[63]
In women with malignancies of other types, however, estrogen replacement
therapy can usually reverse many sexual problems. Providers should discuss
with women the risks and benefits of hormone replacement therapy with
consideration of each women’s individual risk profile. The impact of menopause
on sexual functioning and the arousal phase of the sexual response in
particular are often not communicated to women who struggle to understand
these changes in their sexual responsiveness. Women who have graft-versus-host
disease (GVHD) after bone marrow transplantation may develop vaginal strictures and
adhesions that interfere with intercourse.[64]
For men, chemotherapy agents rarely play an obvious role in erectile
dysfunction.[3] Some cytotoxic agents may cause nerve damage, but few reports
indicate permanent loss of erections upon completion of treatment. Sexual
dysfunction, including loss of desire and erectile dysfunction, is more common
after bone marrow transplant, often associated with autonomic neuropathy or
GVHD.[65,66] Systemic chemotherapy in men occasionally
interferes with testosterone production in the testicles.[67] For those men
who have damage to the testicles from chemotherapy, testosterone replacement
may be necessary to restore sexual function.[3] More rarely, neurotoxic
chemotherapies have been observed to interfere with ejaculation of semen at
orgasm, presumably because of damage to autonomic nerves involved in the
contractions of the prostate, seminal vesicles, and bladder neck.[68]
Treatment-Related Factors Secondary to Radiation
Like chemotherapy, radiation can produce side effects such as fatigue, nausea
and vomiting, diarrhea, and other symptoms that can reduce feelings of
sexuality. In particular, pelvic radiation often irritates the intestinal
lining and may cause diarrhea. The fatigue and change in bowel habits
associated with radiation likely contribute to loss of libido and decreased
sexual activity reported for both men and women.
For women, pelvic radiation also causes changes in the vagina. Both
external-beam radiation and implants damage the vaginal epithelium and basal
layer of the mucosa, leading to vaginal stenosis and vascular fibrosis. These
factors can then lead to long-term sexual dysfunction, painful pelvic
examinations, dyspareunia, potential gonadal toxicity, infertility, and low-birth-weight pregnancy outcomes in survivorship.[69,70] A longitudinal prospective study of sexual function and vaginal changes after radiation therapy for cervical cancer found persistent sexual dysfunction and adverse vaginal changes throughout the 2 years after radiation therapy during which the women were followed; 85% had low or no sexual interest, 35% reported moderate to severe lack of lubrication, 55% had mild to severe dysfunction, and 30% were dissatisfied with their sexual life.[71] Women
who receive radiation should be educated regarding the use of vaginal dilators.
Vascular compromise can be temporary or permanent.[72] For men with rectal cancer, pelvic
radiation has been associated with difficulties attaining or maintaining erection.[73,74]
The exact etiology of sexual dysfunction after radiation therapy remains
unknown [14] but likely relates to arterial damage of the penile arteries, limiting blood flow needed for successful erection.[40] Proposed etiologies include pudendal or sympathetic nerve injury,
vascular occlusion of penile arteries, or decreased levels of testosterone.
Often, sexual changes are insidious, with changes occurring from 6 months to 1 year
after radiation as fibrosis develops. There is a greater risk of sexual
morbidity in men who already have compromised quality of erections before
cancer diagnosis. Other risk factors that contribute to greater risk of sexual
morbidity include cigarette smoking, history of heart disease, hypertension,
pretreatment potency, and/or diabetes.[75]
Treatment-Related Factors Secondary to Hormone Therapy
Hormone therapy for prostate cancer involves reducing circulating androgens as
close to zero as possible. Because androgens also act in the brain to promote
sexual desire, about 80% of men report a profound decrease in sexual interest,
typically accompanied by erectile dysfunction and difficulty reaching
orgasm.[76-79] Younger men, however, are sometimes able to continue adequate
sexual function. With an increasing number of younger men diagnosed with
asymptomatic but advanced prostate cancer found through prostate specific
antigen (PSA) screening, more attention has been given to preventing
some of the sexual morbidity of treatment. Some centers have experimented with
delaying hormone therapy until the onset of symptoms,[80] giving intermittent
hormone therapy as needed to suppress PSA,[81] or using a combination of
finasteride and an androgen-receptor blocker instead of hormone treatments that
totally eliminate androgen production.[82] It is not yet clear, however,
whether men who try these modified treatment regimens are compromising the
length of their survival.
Tamoxifen for breast cancer, described as an antiestrogenic drug, actually acts
like a weak estrogen in the genital tract.[83] The medication has anecdotally
been reported to be associated with vaginal dryness and excessive vaginal
lubrication, soreness, as well as occasional decrease in sexual desire and
orgasmic delay.[84,10] The results of the few studies to examine women’s actual
sexual function while taking tamoxifen are not conclusive or easily compared
because each study utilized different measures and statistical analyses. One
study found no difference in reported sexual problems among women taking
tamoxifen and women who received no systemic therapy, when adjusted for age.[6]
Another study similarly found no significant effect of tamoxifen on sexual
functioning utilizing a different measure and examining the effect only in
women aged 50 years and older.[63] Another study found that use of tamoxifen
did not make a significant independent contribution to the prediction of impact
on sexuality.[85] Results from a study with a limited sample size of
women taking tamoxifen, however, noted a differential estrogen effect by age,
such that an estrogen effect was seen on the vaginal smears of 34 of 49
participants and was more common in older patients (P = .054). The presence of
an estrogen effect was correlated with negative reactions during sex (P = .02)
and vaginal dryness or tightness (P = .046). This study raised the possibility
that tamoxifen may have antagonist effects on the vagina of younger women and
estrogen agonist effects on postmenopausal women.[86] Prospective study of
sexual functioning with evaluation of physiologic status (e.g., vaginal mucosa
and hormone levels) before and after introduction of systemic therapy continues
to be warranted. The impact of tamoxifen on sexuality and mood is still not
clearly understood.
Psychological Factors
Loss of interest in sex is likely to be secondary to psychological factors. It
is not uncommon for both men and women to believe, though incorrectly, that
past sexual activity, an extramarital affair, sexually transmitted disease, or
abortion has caused their cancer. Some believe, again incorrectly, that sexual
activity may promote a recurrence of their tumor. This misbelief is especially
common in individuals with a malignancy of the pelvic or genital area. These
individuals may need reassurance that cancer is not transmissible via sexual
contact. Women with squamous cell carcinoma of the cervix have often read or
been told that this cancer is associated with the sexually transmitted human
papillomavirus.[87] Guilt about past sexual activity or concern about
potential harm to a partner are issues that should be addressed in these
patients. The health care provider can clarify that it is the virus and not
the cancer that is transmissible through sexual contact.
Loss of sexual desire or a decrease in sexual pleasure is a common symptom of
depression. Depression is 15% to 25% more prevalent in patients with cancer
than in the healthy population;[88] therefore, an assessment to rule out
depression is an important part of evaluating sexual dysfunction. Sometimes
people present with complaints of sexual dysfunction, feeling less stigmatized
having a physical medical problem than they do by acknowledging that they are
depressed. Treating depression can be helpful in alleviating sexual
dysfunction. Attention should be paid to the sexual side effects of
antidepressants in clinical decision making. (Refer to the PDQ summary on Depression 4 for more information.)
Changes in body image may interfere with sexual desire in some cancer
survivors, but the impact of disfiguring cancer treatments, such as mastectomy,
has been exaggerated. For example, breast conservation may result in better
self-rated physical attractiveness in women compared with mastectomy alone, but
these groups of women do not differ in their sexual activity or satisfaction.
On the other hand, weight gain after chemotherapy for breast cancer may be
underestimated as a factor that decreases a woman’s feelings of
attractiveness.[89] Having an ostomy for elimination of stool or urine can
also affect a man’s or woman’s sense of being sexually attractive. Specific
coping strategies have been suggested to overcome these problems.[90]
The stress of cancer diagnosis and ongoing therapy can exacerbate underlying
marital tensions. This can likewise affect the sexual relationship. Men or
women who do not have a committed relationship also have to face the potential
trauma of being rejected by a new partner who learns about his or her history
of cancer.[3] Some avoid all dating relationships out of fear of such
rejection. One premorbid personality factor that may play a role in whether a
man or woman stays sexually active after cancer is the sexual self-schema
(i.e., whether an individual regards his or her own sexuality in a positive light). Women
with negative sexual self-schemas were less likely to resume sex or have good
sexual function after treatment for gynecological cancer.[91] One of the most
important factors in adjusting after cancer is the person’s feelings about his
or her sexuality before cancer. That does not mean, however, that this is
not a good opportunity to help a person explore those issues.
References
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Watson M, Wheatley K, Harrison GA, et al.: Severe adverse impact on sexual functioning and fertility of bone marrow transplantation, either allogeneic or autologous, compared with consolidation chemotherapy alone: analysis of the MRC AML 10 trial. Cancer 86 (7): 1231-9, 1999.
[PUBMED Abstract]
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Schover LR, Montague DK, Lakin MM: Sexual problems. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1997, pp 2857-2872.
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Penson DF, Feng Z, Kuniyuki A, et al.: General quality of life 2 years following treatment for prostate cancer: what influences outcomes? Results from the prostate cancer outcomes study. J Clin Oncol 21 (6): 1147-54, 2003.
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Assessment of Sexual Function in People With Cancer
No clear guidelines address sexuality during the stages of disease and its
treatment. When therapeutic decisions are being made, providers should offer
education and information to patients, ideally with the partner present,
regarding known risks of sexual morbidity associated with cancer treatments.
Oncology professionals should assist patients and their partners by asking
specific open-ended questions to validate the importance of sexual health
concerns, thus providing an environment in which the patient and couple are
encouraged and feel safe to express personal concerns. Assessment should be sensitive to the subtle ways in which changes in sexual function affect men’s self-image and masculine identity.[1] Providers should
examine their own thoughts and feelings regarding sexuality. When providers
are not comfortable addressing issues of sexuality, their patient’s concerns
should not be ignored or dismissed. Referrals should be offered to alternate
resources. Although some patients may not want to discuss their sexual health,
providers should at least offer the option, conveying that sex is an
appropriate topic to cover during future visits.
Because sexual function is one important aspect of quality of life, the follow-up
oncology visit is a key opportunity for health care providers to assess whether a
cancer patient is experiencing sexual problems. Although it would be ideal if
an oncologist carried out the sexual assessment, time constraints and lack of
training or comfort in discussing sexual issues often interfere with this goal.
Furthermore, many people who have finished their cancer treatment have their routine follow-up care with a primary practitioner rather than an
oncology specialist. At least in oncology settings, it may be helpful to
designate and train a member of the team, such as an oncology nurse or social
worker, as the expert on sexuality issues. That provider can take
responsibility for asking about a variety of quality-of-life issues, including
relationships and sexuality. A minimal sexual assessment might consist of
asking the following question: “Many cancer survivors notice changes or
problems in their sex lives after cancer treatment. Do you have any problems
or concerns related to sexuality?” Simple problems can be handled with
immediate reassurance or advice, but the oncology team should also build a
network of specialists willing to help cancer patients with sexual issues,
including mental health professionals trained in sex therapy, gynecologists
familiar with women’s concerns about hormone replacement or dyspareunia,
urologists who specialize in treating male sexual dysfunction, and infertility
specialists who can treat younger patients who are interested in having
children.
The literature contains a number of articles and resources that address sexual
assessment,[2] with many specific to cancer patients.[2-5] The Kaplan model
provides a useful interview guide to evaluate sexual problems in healthy and
medically ill individuals, focusing on the chief complaint, sexual status,
psychiatric status, family and psychosocial history, relationship assessment,
summary and recommendations.[6] Kaplan’s model has been applied to oncology
settings, with brief descriptions of the assessment for each part of the
interview.[3,7] The PLISSIT (permission, limited information, specific suggestions, and intensive therapy) model [8] is
another model of assessment and intervention commonly used as a framework for
sexual rehabilitation in cancer care and medical illness.[5,9-12]
General Factors Affecting Sexual Functioning Evaluated in Assessment
Once a possible sexual problem has been identified, the most important
assessment tool for the oncology health provider is a clinical interview with
an individual man or woman, or with a couple.[13] The following brief list of
factors known to impact current sexual functioning should be included in an
assessment; the patient’s specific sexual concerns or needs at the time dictate
the approach and content of the discussion.
Current sexual status
In the evaluation of an individual’s sexual function, the initial phase of
assessment serves to clarify the nature of the individual’s problem and/or
complaint. A variety of aspects of current sexual function should be
addressed, including the frequency of experiencing spontaneous desire for sex;
ease of feeling subjective pleasure with sexual stimulation; and signs of
physiological arousal, including the ability to achieve and maintain a firm
erection for a man, and vaginal expansion and lubrication for a woman. The
ability to reach an orgasm is another important measure of sexual function. It
is helpful to ask what types of sexual stimulation can trigger an orgasm (i.e.,
self-touch, use of a vibrator or shower massage, partner caressing, oral
stimulation, or intercourse). Pain in the genital area that occurs with sexual
activity should be described in detail: “Where is the pain? What does it feel
like? What kinds of sexual activity trigger it? Does it happen every time? How
long does it last?” When these lines of inquiry elicit a sexual problem, the
interviewer should ask when the problem began, especially whether a cancer
diagnosis or particular treatment occurred close in time to onset of the
problem. Because many people who have cancer take prescription medications that
can interfere with sexual function, including antihypertensives,
antidepressants, or psychotropic medications, the interviewer should find out
whether a new medication or change of dosage was prescribed at the problem’s onset.
Premorbid sexual functioning
An individual’s past (pre-illness) sexual development, preferences, and
experience are vital to assessment of sexual status. The level of sexual
functioning before diagnosis and treatment, interest, satisfaction, and
importance of sexual functioning in the relationship all influence the
patient’s potential distress related to current sexual status. Individuals who
have already experienced sexual difficulties may be especially vulnerable to
the effects of treatment.[14] Clinicians should be careful not to make assumptions
regarding the patient’s previous sexual experience or the importance of sexual
expression.
Psychosocial Aspects of Sexuality
Relationship status
The patient may or may not have an available partner at the time of diagnosis.
Sexuality should be taken no less seriously by the clinician or the patient if there is no partner. For patients with a partner, the clinician should consider
and discuss the duration, quality, and stability of the relationship before
diagnosis. Additionally, as many patients fear rejection and abandonment, the
clinician should inquire about the partner’s response to the illness and the
patient’s concerns about the impact of treatment on the partner.[15-17] Partners
share many of the same reactions as patients in that their most significant
concerns typically relate to loss and fear of death. Moreover, the partner’s
physical, sexual, and emotional health should be considered relative to his/her
previous and current sexual status in a complete assessment. A clinician
should recognize that most couples experience difficulty discussing sexual
preferences, concerns, and fears even under ideal circumstances and that sexual
communication problems tend to worsen with illness and threat of death.
Psychological status
The affective spectrum during cancer treatment ranges from disbelief to
clinical depression and typically changes over time. Anxiety and depression
are the two most common affective disruptions among patients with cancer and
both have been found to have deleterious effects on sexual
functioning.[3-5,7,18] A clinician should be aware of current mental status
and any history of depression or other psychiatric disorder, previous
psychotherapy, treatment with psychotropic medication, and/or hospitalizations.
Current use of psychotropic medications should also be reviewed with respect to
impact on sexual function. Cancer treatment can produce changes to the body that
negatively impact body image and self-esteem.[4,5,19] Commonly, patients have
difficulty seeing themselves as sexually attractive during and after treatment.
Identifying body-image disturbances is important to incorporate into goals of
care and rehabilitation. Frequently, the couple experiences changes of social
roles during treatment. An individual’s identity and sense of worth may be
threatened when role changes occur.[4,15] The partner’s participation in the
patient’s physical care often negatively impacts feelings of sexuality.
Younger couples, more than older couples, may be vulnerable to problems with
playing alternative or new domestic roles and experiencing the myriad life
and financial stressors associated with treatment.[4]
Medical Aspects of Sexuality
The clinician should ascertain past medical history with a particular emphasis
on other concurrent medical illness for which the patient is receiving
treatment. Comorbidity contributes to risk of sexual dysfunction and
additional decrease in social and role functioning, mental health, and health
perceptions. Medical illnesses that impact the endocrine, vascular, and
nervous systems are all known to have a potential deleterious effect on the
sexual response cycle.[13,20,21] Diabetes, hypertension, vascular disease,
multiple sclerosis, and many other disorders impact sexual function,
particularly the quality of erections in men. Two textbooks extensively review
the impact of chronic illness and disability on sexual function.[13,21]
Lifestyle factors, including smoking and substantial alcohol consumption, are
also risk factors of sexual morbidity. In men, cigarette smoking may induce
vasoconstriction and penile venous leakage;[20] in large amounts, alcohol is a
strong sedative-hypnotic producing decreasing libido and transient erectile
dysfunction.[20]
Pharmacologic treatment for cancer and chronic illness in general is often a
necessary and integral component of health maintenance. Some pharmacologic
treatments, however, may have direct or indirect deleterious effects on sexual
function through multiple physiologic and psychologic pathways. Pharmacologic
agents that may negatively affect sexual response are addressed in the section
on pharmacologic effects. A number of resources provide further delineation of
the mechanisms for changes in sexual function associated with these agents and
include listings of specific medications and known effects on sexual
function.[4,22-24]
Brief questionnaires that measure sexual dysfunction may be helpful,
particularly when screening larger groups of cancer patients for sexual
dysfunction or when conducting research on sexuality as an aspect of quality of
life. The International Index of Erectile Function (IIEF, 15 items) and the Brief Sexual Male Functioning Inventory (BMSFI, 11 items) are well-validated scales
measuring aspects of sexual function and satisfaction in men.[25,26] Sexual problems can also be identified with a briefer five-item scale, the Sexual Health Inventory for Men (SHIM), which is a validated self-report scale that can be used to identify erectile dysfunction in a variety of clinical settings.[26] For women, there are several brief measures with established psychometric properties that assess sexual functioning and satisfaction: the Brief Index of Sexual Functioning for Women (BISF-W, 22 items), the Sex History Form (SHF, 46 items), the Changes in Sexual Functioning Questionnaire (CSFQ, 35 items), the Derogatis Interview for Sexual Functioning (DISF/DISF-SR, 25 items), the Female Sexual Function Index (FSFI, 19 items), and the Golombok-Rusk Inventory of Sexual Satisfaction (GRISS, 28 items).[27,28,13]
These scales vary in their reliability, validity, method of attainment (i.e.,
patient vs. clinician rates; structured vs. semistructured), type and
number of symptoms assessed, and time frame of assessment. To accurately
reflect changes over time, one must obtain systematic assessment of premorbid,
baseline, and follow-up levels of sexual function and satisfaction.
In addition to paper-and-pencil self-report measures of sexuality, some medical
evaluations of the adequacy of the physiological response are available.[29]
For men, some of the more useful evaluations include the Rigiscan, a
computerized electronic instrument that measures the adequacy of nocturnal
erections; penile ultrasound studies to document hemodynamics of erection; and
hormonal assays. In women, the use of the vaginal maturation index to measure
estrogenization, a careful pelvic examination to identify sources of pain that
occur during sexual activity, and hormonal assays are most common. More
sophisticated measures of vaginal blood flow or sensory thresholds have been
studied but have not gained wide acceptance.
Review of the literature highlights the need for prospective studies with
longer-term follow-up, validated measures, and larger sample sizes. In
particular, issues of sexual recovery in women have received too little
clinical attention and research.
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Auchincloss SS: Sexual dysfunction in cancer patients: issues in evaluation and treatment. In: Holland JC, Rowland JH, eds.: Handbook of Psychooncology: Psychological Care of the Patient With Cancer. New York, NY: Oxford University Press, 1989, pp 383-413.
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Schover LR: Sexuality and Fertility After Cancer. New York, NY: John Wiley and Sons, 1997.
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Lamb MA: Sexuality and Sexual Functioning. In: McCorkle R, Grant M, Frank-Stromborg M, et al., eds.: Cancer Nursing: A Comprehensive Textbook. 2nd ed. Philadelphia, Pa: WB Saunders Co, 1996, pp 1105-1127.
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Kaplan HS: The Evaluation of Sexual Disorders: Psychological and Medical Aspects. New York, NY: Brunner/Mazel Inc, 1983.
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Auchincloss S: Sexual dysfunction after cancer treatment. Journal of Psychosocial Oncology 9 (1): 23-42, 1991.
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Annon JS: The Behavioral Treatment of Sexual Problems. Vol 1. Honolulu, Hawaii: Enabling Systems, Inc, 1975.
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Penson RT, Gallagher J, Gioiella ME, et al.: Sexuality and cancer: conversation comfort zone. Oncologist 5 (4): 336-44, 2000.
[PUBMED Abstract]
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Gallo-Silver L: The sexual rehabilitation of persons with cancer. Cancer Pract 8 (1): 10-5, 2000 Jan-Feb.
[PUBMED Abstract]
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Sipski ML, Alexander CJ: Impact of disability or chronic illness on sexual function. In: Sipski ML, Alexander CJ, eds.: Sexual Function in People With Disability and Chronic Illness. Gaithersburg, Md: Aspen Publishers, Inc, 1997, pp 3-9.
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Waldman TL, Eliasof B: Cancer. In: Sipski ML, Alexander CJ, eds.: Sexual Function in People With Disability and Chronic Illness. Gaithersburg, Md: Aspen Publishers, Inc, 1997, pp 337-354.
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Schover LR, Jensen SB: Sexuality and Chronic Illness: A Comprehensive Approach. New York, NY: The Guilford Press, 1988.
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Talcott JA, Manola J, Clark JA, et al.: Time course and predictors of symptoms after primary prostate cancer therapy. J Clin Oncol 21 (21): 3979-86, 2003.
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McNeff EA: Issues for the partner of the person with a disability. In: Sipski ML, Alexander CJ, eds.: Sexual Function in People With Disability and Chronic Illness. Gaithersburg, Md: Aspen Publishers, Inc, 1997, pp 595-616.
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Stead ML: Sexual function after treatment for gynecological malignancy. Curr Opin Oncol 16 (5): 492-5, 2004.
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Wimberly SR, Carver CS, Laurenceau JP, et al.: Perceived partner reactions to diagnosis and treatment of breast cancer: impact on psychosocial and psychosexual adjustment. J Consult Clin Psychol 73 (2): 300-11, 2005.
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Wise TN: Sexual functioning in neoplastic disease. Med Aspects Hum Sex 12: 16-31, 1978.
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Whipple B, McGreer KB: Management of female sexual dysfunction. In: Sipski ML, Alexander CJ, eds.: Sexual Function in People With Disability and Chronic Illness. Gaithersburg, Md: Aspen Publishers, Inc, 1997, pp 511-536.
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Lue TF: Contemporary Diagnosis and Management of Male Erectile Dysfunction. Newton, Pa: Handbooks in Health Care, 1999.
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Sipski ML, Alexander CJ, eds.: Sexual Function in People With Disability and Chronic Illness. Gaithersburg, Md: Aspen Publishers, Inc, 1997.
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Crenshaw TL, Goldberg JP: Sexual Pharmacology: Drugs That Affect Sexual Functioning. New York, NY: WW Norton & Company, 1996.
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Weiner DN, Rosen RC: Medications and their impact. In: Sipski ML, Alexander CJ, eds.: Sexual Function in People With Disability and Chronic Illness. Gaithersburg, Md: Aspen Publishers, Inc, 1997, pp 85-118.
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Drugs that cause sexual dysfunction: an update. Med Lett Drugs Ther 34 (876): 73-8, 1992.
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Rosen RC, Riley A, Wagner G, et al.: The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 49 (6): 822-30, 1997.
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Rosen RC: Evaluation of the patient with erectile dysfunction: history, questionnaires, and physical examination. Endocrine 23 (2-3): 107-11, 2004 Mar-Apr.
[PUBMED Abstract]
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Althof SE, Rosen RC, DeRogatis L, et al.: Outcome measurement in female sexual dysfunction clinical trials: review and recommendations. J Sex Marital Ther 31 (2): 153-66, 2005 Mar-Apr.
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Meston CM, Derogatis LR: Validated instruments for assessing female sexual function. J Sex Marital Ther 28 (Suppl 1): 155-64, 2002.
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Schover LR, Montague DK, Lakin MM: Sexual problems. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1997, pp 2857-2872.
Pharmacological Effects of Supportive Care Medications on Sexual Function
The following sections describe the effects of various commonly used
medications on sexual function in people with cancer. People undergoing cancer
treatment are often treated with multiple medications that can cause diminished
desire or other difficulties in sexual functioning, which can add to the impact
of surgery, radiation, and chemotherapy on sexuality. Medications may
adversely affect one or more of the physiologic mechanisms (i.e., vascular, hormonal,
neurologic) that underlie normal sexual function. Drug therapy may also affect
sexual functioning indirectly through concomitant effects on mental alertness,
mood state, and/or social interactions. The evaluation of sexual problems in
people with cancer must, therefore, be comprehensive and attuned to the
multiple etiologies of these difficulties. The following sections may be
helpful in identifying some of the possible medication side effects, though
more than one may play a role in an individual.
Effect of Opioids on Sexual Function
Reduced libido is a well-known phenomenon for those using heroin or participating in a
methadone maintenance program. Unfortunately, this effect is poorly understood
by clinicians prescribing opioids for pain. Animal studies confirm that
opioids lower testosterone levels and suppress sexual function in males.[1]
Early case studies of persons using heroin or methadone described diminished
libido, sexual dysfunction, reduced testosterone levels in men, and amenorrhea
in women.[2-7] Two mechanisms are thought to be responsible for the reported
reduction in libido associated with opioid use. Opioids inhibit the production
of gonadotropin-releasing hormone, subsequently decreasing the release of
luteinizing hormone (LH), thus decreasing the production of testosterone.
Opioids also produce hyperprolactinemia, which causes negative feedback on the
release of LH and decreases the production of testosterone.[8] Opioids are
known to alter the normal function of the hypothalamic-pituitary-gonadal
axis.[9] These effects resolve after the opioid has been discontinued. Other case reports of patients receiving opioids for relief of chronic pain
suggest these same findings.[10-12] Another case-control study examined the effects of chronic oral opioid administration in survivors of cancer and, consistent with the research on intrathecal administration, found marked central hypogonadism among the opioid users with significant symptoms of sexual dysfunction, depression, and fatigue.[12] Although the limited research that has
examined the relationships among sexual functioning, chronic pain, opioid
therapy, and testosterone levels has been predominantly evaluated in men,
anecdotal clinical experience supports similar relationships in women. Empirical support has been documented for women in a study that examined the
endocrine consequences of long-term intrathecal administration of opioids.
Reduced libido was reported in 95% of the men and 68% of the women, with
significant reduction in serum LH for both groups and in serum testosterone for
the men. All of the premenopausal women (n = 21) developed either amenorrhea or
an irregular menstrual cycle, with ovulation in only one woman.[13]
The long-term effects of reduced testosterone and amenorrhea are not well
known. Sexuality is an important component of one’s quality of life,
especially for cancer survivors, but also for some people with advanced
disease. Patients may report a history of changes in libido and sexual
dysfunction. If these changes are distressing to the patient, serum total- and
free-testosterone levels and prolactin levels may be obtained.[14] Should the
patient seek improvement in libido and performance, treatment is often
empirical, keeping in mind that there are many potential causes of changes in
sexual function. Treatment options may include using nonopioids for pain,
adding adjuvant analgesics in the hope that the opioid dose may be reduced, or
replacing testosterone through injections, a patch, or gel if not
contraindicated.[15] More research is needed to understand the relationship
between opioids and sexual function, as well as the most effective treatment
strategies.
Selective Serotonin-Reuptake Inhibitors
Decreased sexual desire is a frequent symptom of depression, and sexual
impairment in depressed patients has been consistently confirmed in controlled
studies.[16,17] Continued recognition of the difficulty in
discerning the subjective complaints that are a part of the depressive
syndrome, the consequences of treatment, a pre-existing sexual dysfunction, or
a combination of these factors is needed. Approximately one third of depressed patients
without medication treatment report reduced sexual desire, anorgasmia, delayed
ejaculation, or erectile dysfunction.[18] Selective serotonin-reuptake inhibitors (SSRIs), tricyclics, monoamine oxidase inhibitors, and lithium have all been associated with sexual dysfunction.[19,20]
Sexual desire is mediated through the central nervous system by the
reception of sensory stimuli and the subsequent interpretation through the
limbic system and prefrontal cortex.[21] Additionally, the hypothalamic and
preoptic nuclei contribute to the mediation of this process. Serotonin
inhibits hypothalamic arousal postsynaptic receptors resulting in the release
of excitatory neurotransmitters. These neurotransmitters are responsible
for the activation of the erectile centers of the spinal column. Upon
activation of the erectile centers, subsequent erection, orgasm, and
detumescence occur in males, whereas genital vasocongestion, vaginal lubrication,
and clitoral enlargement occur in females.[22] Physiologically, serotonin is
stored in synaptosomal vesicles awaiting another impulse for release. SSRIs
inhibit this uptake mechanism, which results in the pooling of serotonin in the
synaptic space.[21,23] The excess serotonin causes the postsynaptic
receptors to down-regulate, resulting in decreased stimulation of the lower
erectile centers. It is this action that is thought to be the principal
mechanism for SSRI-induced sexual dysfunction.
There are no well-controlled studies that evaluate the effects of SSRIs on
sexual function within the oncology patient population. There are several
studies, however, that have examined the effects of fluoxetine (Prozac),
fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft) on sexual
function in patients being treated for depression or obsessive-compulsive
disorder. There are few data regarding the prevalence of sexual
dysfunction with the use of citalopram (Celexa) in the treatment of depression.
Sexual dysfunction from SSRIs has generally been reported to affect
approximately 1% to 15% of patients in clinical trials of these medications in
physically healthy depressed patients. Other studies, however, report
significantly higher rates of sexual dysfunction that may more accurately
reflect the incidence typical of clinical practice. A large-scale
retrospective nonrandomized comparison trial of 596 psychiatric outpatients
(167 men, 429 women) treated for at least 6 months with sertraline (n = 170),
fluoxetine (n = 298), venlafaxine (n = 36), or paroxetine (n = 265) found that
symptoms of sexual dysfunction were spontaneously reported by approximately 20%
of patients overall and were more common in men (23.4%) and married
individuals of both genders. The rates of sexual dysfunction associated with
each of the SSRIs were the following: sertraline (16%), fluoxetine (20%),
paroxetine (22%), and venlafaxine (38%). For this sample, the most common sexual
symptoms reported were orgasmic delay or anorgasmia, followed by decreased
desire and arousal difficulties.[24] A prospective multicenter study of 344
patients (152 men, 192 women) with mixed psychiatric disorders treated
with SSRIs and systematic inquiry of sexual dysfunction by the physician found
the frequency of sexual side effects was highest for paroxetine (65%), followed
by fluvoxamine (59%), sertraline (56%), and fluoxetine (54%).[25] Paroxetine
produced significantly greater delay of orgasm or ejaculation (48%) and more
frequent erectile dysfunction and vaginal lubrication difficulties than
sertraline (37% and 16%), fluvoxamine (31% and 10%), or fluoxetine (34% and 16%).
Loss of libido and anorgasmia were more severe in women, though men reported
a greater frequency of sexual dysfunction. The effects of SSRIs are dose
related and may vary among the group. The incidence of sexual dysfunction
obtained by patient self-report does not appear to reflect the true incidence
of sexual dysfunction associated with antidepressant therapy, and systematic
inquiry by providers is needed as sexual dysfunction may be an unrecognized
cause of noncompliance.[26] Two critical reviews of the effects of SSRIs on
sexual function are available.[26,27]
For individuals with premature ejaculation, SSRIs provide an effective
treatment. In a recent double-blind placebo-controlled trial of men with
lifelong rapid ejaculation, paroxetine delayed ejaculation the most, and
fluvoxamine delayed ejaculation the least. Daily doses of 20 mg of paroxetine
and 20 mg of fluoxetine may be regarded as effective treatments for lifelong
rapid ejaculation.[28] Cancer patients treated with these medications in
clinical situations may have higher rates of anorgasmia, decreased sexual
desire, and other problems, possibly because these medications
compound the difficulties cancer patients encounter from multiple etiologies.
There are several possible interventions in the management of SSRI-induced
sexual dysfunction. An obvious, though not always appropriate, possibility is
to decrease the dosage of the SSRI. Altering the timing of SSRI
administration, either by delaying doses until after intercourse or dosing
immediately before intercourse,[29] may be an effective intervention. There
are published data to suggest a drug-holiday intervention over the
weekend can improve the sexual dysfunction induced by SSRIs.[30] Another
possibility is the addition of another medication to help in the control of
SSRI-induced sexual dysfunction or consideration of another antidepressant
with less known sexual side effects. In a randomized, double-blind,
multicenter trial comparison of sustained-release bupropion (bupropion SR) and
sertraline, both were found to be similarly efficacious in the treatment of
outpatients with moderate-to-severe depression. There was a significantly
greater percentage of sertraline-induced sexual dysfunction (63% and 41% of men
and women, respectively), however, compared with bupropion SR–induced sexual
dysfunction (15% and 7%, respectively).[31]
A definitive treatment has not been established for SSRI-induced sexual
dysfunction in males or females. The oncology patient population presents with
significantly more obstacles in the management of sexual dysfunction, as
compared with patients whose symptoms are being managed with SSRIs for depression alone. The
etiology of sexual dysfunction in cancer patients is multifactorial and
complex. The above data are intended to provide practitioners and patients
with possible options in the management of SSRI-induced sexual dysfunction.
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Pelosi MA, Sama JC, Caterini H, et al.: Galactorrhea-amenorrhea syndrome associated with heroin addiction. Am J Obstet Gynecol 118 (7): 966-70, 1974.
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Cicero TJ, Bell RD, Wiest WG, et al.: Function of the male sex organs in heroin and methadone users. N Engl J Med 292 (17): 882-7, 1975.
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Chan V, Wang C, Yeung RT: Effects of heroin addiction on thyrotrophin, thyroid hormones and porlactin secretion in men. Clin Endocrinol (Oxf) 10 (6): 557-65, 1979.
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Spagnolli W, Torboli P, Mattarei M, et al.: Calcitonin and prolactin serum levels in heroin addicts: study on a methadone treated group. Drug Alcohol Depend 20 (2): 143-8, 1987.
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Gulliford SM: Opioid-induced sexual dysfunction. Journal of Pharmaceutical Care in Pain and Symptom Control 6 (2): 67-74, 1998.
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Mirin SM, Meyer RE, Mendelson JH, et al.: Opiate use and sexual function. Am J Psychiatry 137 (8): 909-15, 1980.
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Paice JA, Penn RD, Ryan WG: Altered sexual function and decreased testosterone in patients receiving intraspinal opioids. J Pain Symptom Manage 9 (2): 126-31, 1994.
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Paice JA, Penn RD: Amenorrhea associated with intraspinal morphine. J Pain Symptom Manage 10 (8): 582-3, 1995.
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Rajagopal A, Vassilopoulou-Sellin R, Palmer JL, et al.: Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids. Cancer 100 (4): 851-8, 2004.
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Abs R, Verhelst J, Maeyaert J, et al.: Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab 85 (6): 2215-22, 2000.
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Govier FE, McClure RD, Kramer-Levien D: Endocrine screening for sexual dysfunction using free testosterone determinations. J Urol 156 (2 Pt 1): 405-8, 1996.
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Munarriz R, Maitland S, Garcia SP, et al.: A prospective duplex Doppler ultrasonographic study in women with sexual arousal disorder to objectively assess genital engorgement induced by EROS therapy. J Sex Marital Ther 29 (Suppl 1): 85-94, 2003.
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Nofzinger EA, Thase ME, Reynolds CF 3rd, et al.: Sexual function in depressed men. Assessment by self-report, behavioral, and nocturnal penile tumescence measures before and after treatment with cognitive behavior therapy. Arch Gen Psychiatry 50 (1): 24-30, 1993.
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Thase ME, Reynolds CF 3rd, Jennings JR, et al.: Nocturnal penile tumescence is diminished in depressed men. Biol Psychiatry 24 (1): 33-46, 1988.
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Mathew RJ, Weinman M, Claghorn JL: Tricyclic side effects without tricyclics in depression. Psychopharmacol Bull 16 (3): 58-60, 1980.
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Crenshaw TL, Goldberg JP: Sexual Pharmacology: Drugs That Affect Sexual Functioning. New York, NY: WW Norton & Company, 1996.
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Fleming MP, Paice JA: Sexuality and chronic pain. J Sex Educ Ther 26 (3): 204-14, 2001.
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Sanders-Bush E, Mayer SE: 5-Hydroxytryptamine (serotonin) receptor agonists and antagonists. In: Hardman JG, Limbird LE, Molinoff PB, et al., eds.: Goodman & Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996, pp 249-263.
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Frye CB, Berger JE: Treatment of sexual dysfunction induced by selective serotonin-reuptake inhibitors. Am J Health Syst Pharm 55 (11): 1167-9, 1998.
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Matsumoto AM: Endocrine and reproductive diseases. In: Bennett JC, Plum F, eds.: Cecil Textbook of Medicine. 20th ed. Philadelphia, Pa: WB Saunders, 1996, pp 1328-1329.
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Keller Ashton A, Hamer R, Rosen RC: Serotonin reuptake inhibitor-induced sexual dysfunction and its treatment: a large-scale retrospective study of 596 psychiatric outpatients. J Sex Marital Ther 23 (3): 165-75, 1997 Fall.
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Montejo-González AL, Llorca G, Izquierdo JA, et al.: SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther 23 (3): 176-94, 1997 Fall.
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Lane RM: A critical review of selective serotonin reuptake inhibitor-related sexual dysfunction; incidence, possible aetiology and implications for management. J Psychopharmacol 11 (1): 72-82, 1997.
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Rosen RC, Lane RM, Menza M: Effects of SSRIs on sexual function: a critical review. J Clin Psychopharmacol 19 (1): 67-85, 1999.
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Segraves RT, Kavoussi R, Hughes AR, et al.: Evaluation of sexual functioning in depressed outpatients: a double-blind comparison of sustained-release bupropion and sertraline treatment. J Clin Psychopharmacol 20 (2): 122-8, 2000.
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Olivera AA: Sexual dysfunction due to clomipramine and sertraline: nonpharmacological resolution. J Sex Educ Ther 20 (2): 119-122, 1994.
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Waldinger MD, Hengeveld MW, Zwinderman AH, et al.: Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline. J Clin Psychopharmacol 18 (4): 274-81, 1998.
[PUBMED Abstract]
Treatment of Sexual Problems in People With Cancer
Although research is beginning to clarify the frequency and types of sexual problems people
with cancer experience, few treatment programs for sexual dysfunction in
cancer patients have been designed or tested. Programs that integrate medical and psychological modalities aimed at the treatment of sexual dysfunction in those who have had cancer are warranted. Additionally, these programs must be cost-effective and accessible to people with cancer.
Many patients are fearful or anxious of their first sexual experience after
treatment and can often begin a pattern of sexual avoidance. If the patient is
concerned about sending mixed signals to his or her partner, this can lead to
avoidance of general intimacy and touch. The partner may also contribute
to the generalized avoidance of intimacy through his or her reluctance to initiate
any behavior that may be perceived as pressure to be more intimate or may contribute to any potential physical discomfort from greater expression of
physical intimacy. Providers need to reassure patients and their significant
others that even when intercourse is difficult or impossible, their sex lives
are not over. The couple can give and receive pleasure and satisfaction by
expressing their love and intimacy with their hands, mouths, tongues, and lips.
Providers should encourage the couple to express affection in alternative ways
(e.g., hugging, kissing, nongenital touching) until they feel ready to resume sexual
activity. The couple should be encouraged to communicate honest feelings,
concerns, and preferences.
If a man cannot attain an erection firm enough for penetration,
and/or if intercourse is painful for a woman, some couples may be willing to find
alternative ways to bring each other to orgasm and express sexual intimacy.
Sensate focus exercises of noncoital pleasuring,[1,2] based on principles of
sensuous massage, give couples an experience of sexual expression that allows
them to be physically close and intimate without pressure and anxiety that can
be associated with anticipation of intercourse. The structure and ground rules
of sensate focus can help bypass performance anxiety (self-consciousness and
self-evaluation) and enable the couple to lose themselves in the current
experience of pleasurable touch. These exercises also help the couple
communicate about potentially problematic or emotionally sensitive areas of the
body. Providers should determine a couple’s openness to modification of their
sexual technique.
As many patients will experience anticipatory anxiety about re-establishing
sexual intimacy with their partner and potential uncertainty of their own
sexual response, the potential advantages of self-stimulation can be explored.
Self-stimulation has the advantage of allowing the individual to become
comfortable with his/her sexual response and arousal without the added pressure
of performance anxiety commonly heightened by concern for their partner’s
pleasure, reactions, concerns, and/or fears. For many individuals, a
cognitive reframing of masturbation to self-stimulation or self-pleasuring
allows the individual to accept this activity as part of the process in sexual
rehabilitation. For others, this behavior may still be a resilient and
persistent taboo for cultural and religious reasons.
For those couples who wish to have sexual intercourse, sexual positions that
place no weight on a scar or ostomy and positions that allow better
control of depth of penetration can be explored. The side-by-side position
(spooning) in which the man is behind the woman, or the L-shaped position, with
both partners lying down, torsos at right angles and legs entwined, are two
possibilities. Comprehensive pamphlets on sexuality and cancer, for both men
[3] and women,[4] provide illustrations of sexual positions and other
self-help information.
For patients with colostomies or ileostomies, pamphlets are available from
national organizations related to resuming sexual activity including topics
such as sex and the female ostomate, sex and the male ostomate, and gay and
lesbian ostomates. Providers can educate patients on limiting food intake
before anticipated sexual activity, watching the types of food consumed, and
planning times for intimacy when a bowel movement is less likely. Although the
ostomy pouch is typically changed when about one-third full, patients should be
taught to empty the pouch sooner when anticipating sexual intimacy. Patients may fear that the ostomy bag will interfere with
sexual intimacy, become dislodged, or cause damage to the stoma. An empty and
flat ostomy bag will not become dislodged from the stoma and can be rolled up
or taped down so that it will not get in the way of sexual intimacy.
Decorative covers may also be worn.[5,6] A much greater selection of products
for ostomates exists today than in years past, including disposable pouches, reusable pouches that
empty from the bottom or top while still attached, pouches with filters to
control odors, and pouches that hang sideways instead of down for physical
activity. Patients concerned about potential odor can use deodorant tablets or
liquids in the bottom of the pouch or as recommended by the manufacturer.[6]
Providers can help educate couples by offering practical suggestions to
overcome changes in responsiveness to sexual stimulation. Couples should allow
plenty of time for sexual expression with sufficient foreplay to develop the
fullest possible sexual arousal. For some couples, early morning may be a good
restful time for sexual expression. Conditions that facilitate sexual pleasure
should be explored and may include relaxation, dreams, fantasy, deep breathing,
and recalling positive experiences with the partner.
Erection problems are the most common sexual dysfunction for which men seek
help after cancer treatment. Many men with erectile dysfunction are able to
have an orgasm with oral or manual stimulation; many partners are satisfied and
orgasmic with noncoital stimulation. If the desire for intercourse remains,
there are several treatment options available for erectile dysfunction
depending on the cause and degree of dysfunction. Only a small percentage of
men with erection problems seek help.[7,8] With the advent of
sildenafil (Viagra), a phosphodiesterase-5 (PDE-5) inhibitor to treat erection problems,[9] the
percentage of men who enter into the treatment system for erection problems has
increased. Despite the publicity about the effectiveness of sildenafil, it
works best in men with the mildest forms of erectile dysfunction. Many men
will not be able to achieve adequate erections by taking this drug alone. Sildenafil use allows about 72% of patients with nerve-sparing prostatectomy and 15% of patients with non–nerve-sparing prostatectomy to achieve vaginal intercourse.[10] About 12% of sildenafil responders lose efficacy by 3 years.[11] In a
study of brachytherapy in the treatment of localized prostate cancer,
sildenafil improved potency in 62% to 70%.[12] Patients who were not being treated with
androgen therapy had a significantly better response.[13] Similarly, of men
who became impotent after brachytherapy for prostate cancer,[14] 85% to 88% responded
with improved erectile function when taking sildenafil. Reported potency rates after prostate brachytherapy are high; a 3-year follow-up study demonstrated that 80% of patients were able to have adequate erections for satisfactory sexual activity with or without siladenafil.[15] Sildenafil has also improved erectile function for patients with partial parasympathetic nerve disruption from rectal surgery.[16,17] No other treatment
for erectile dysfunction has a high rate of patient acceptance. Sildenafil has been studied in a novel primary prevention modality using nightly administration after a bilateral nerve-sparing prostatectomy. This approach effected a sevenfold improvement in return of spontaneous, normal erectile function 2 months after discontinuation of the drug.[18] The authors state that this effect appears to be mediated by properties unique to sildenafil that include improved endothelial function and neuronal regeneration and neuroprotection.[18] Published data also suggest that early use of sildenafil after radical retropubic prostatectomy may preserve intracoporeal smooth muscle content;[19] although this effect on the return of potency is not known, maintaining the pro-erectile ultrastructure is integral to rehabilitating post–radical retropubic prostatectomy erectile function.[19] Data on the efficacy of early postoperative erectile treatment rely on very few randomized trials. Larger randomized trials with at least 2 years of follow-up are needed before definitive conclusions can be drawn about the true efficacy of rehabilitative sexual therapy for postoperative erectile function, as the natural recovery of erectile function has been reported to take as long as 2 years.[20]
Currently, there are three U.S. Food and Drug Administration (FDA)–approved PDE-5 inhibitors on the market: Viagra (sildenafil), Levitra (vardenafil), and Cialis (tadalafil). Although all three of these oral medications are PDE-5 inhibitors, they are not the same. No head-to-head comparison trials have been published. It appears, however, that all three agents are similar in efficacy, helping 60% to 70% of patients with erectile dysfunction.[21-23] However, comparisons of the efficacy of the PDE-5 inhibitors are complicated by the heterogeneity of the populations studied, the varied primary cancer therapies employed, different timing in measuring outcomes in the clinical trials, and variance in the endpoints used to determine efficacy. Furthermore, most of these trials were industry sponsored.
The major contraindications for use of a PDE-5 inhibitor are concurrent use of nitrates or the alpha-blockers terazosin (Hytrin) and doxazosin (Cardura). The major difference in the three approved inhibitors is that tadalafil has a considerably longer serum half-life, which provides both a larger window of opportunity and potential side effects.[21,22] There is far more research on the use of sildenafil than on the use of the other PDE-5 inhibitors in oncology patients, as it was approved in 1998; vardenafil and tadalafil were approved in 2003. Tadalafil was investigated in the treatment of erectile dysfunction following bilateral nerve-sparing radical retropubic prostatectomy. Results from this randomized, double-blind, placebo-controlled, multicenter study found that 71% of patients randomly assigned to receive tadalafil reported improved erections.[24] Vardenafil had been investigated in the treatment of erectile dysfunction after radical retropubic prostatectomy and following nerve-sparing radical prostatectomy.[25,26] In post–radical retropubic prostatectomy patients, the average intercourse success rate per patient receiving 20 mg of vardenafil was 74% in men with mild to moderate erectile dysfunction and 28% in men with severe erectile dysfunction, compared with 49% and 4% for placebo.[25] Patients receiving 10-mg and 20-mg doses of vardenafil following nerve-sparing radical prostatectomy reported significantly greater intercourse satisfaction, orgasmic function, and overall satisfaction rate with hardness on the International Index of Erectile Function (IIEF), compared with those receiving placebo.[26]
Therapies such
as penile injections, vacuum devices, or intraurethral medication have
extremely high dropout rates, and of men who seek help at clinics for erectile
dysfunction, only about one third feel long-term satisfaction, despite trying a
mean of two different treatment modalities.[27-30] For men who have a suboptimal response to oral therapies after radical retropubic prostatectomy, the use of combined intracorporal injection (ICI) and a PDE-5 inhibitor has been shown to improve erectile function. One retrospective study found that among men who experienced erectile dysfunction after nerve-sparing retropubic prostatectomy, 68% who combined ICI with either sildenafil or vardenafil reported improved erectile function. On follow-up, 36% of these patients used ICI therapy only intermittently, as they reportedly felt that this was adequate for good results.[31]
Rates of long-term
satisfaction are superior for penile prosthesis surgery,[32-34] but with less
invasive and permanent treatments available, fewer men choose this treatment
modality, particularly after undergoing intensive cancer therapy.[35] The role of
the man’s partner in prompting him to try a treatment or to keep on using it is
also poorly understood. When erectile functioning is impaired, counseling
should initially focus on obtaining sexual pleasure and satisfaction without
erections or intercourse. For men with postsurgical erectile dysfunction,
there is the possibility for improved function over time as nerves may
potentially regenerate for up to 2.5 years after surgery.[6]
Providers should educate patients that opting to use no medical intervention to restore
erections is also a valid choice. Comprehensive reviews of the current
management of erectile dysfunction are available.[36-40] Also, several authors
[37,41,42] provide further discussion on the management of inhibited sexual
desire and other male sexual dysfunctions.
When women experience changes in arousal, most notably vaginal dryness and
irritation, vaginal moisturizers (e.g., Replens) and water-based lubricants
(e.g., Astroglide and K-Y Liquid) should be suggested, especially in women who
cannot use estrogen replacement. The approval of the estradiol-releasing vaginal ring (Estring),
containing a slow-release preparation, 2 mg of micronized 17-beta-estradiol, may also provide a less risky alternative to systemic estrogen
replacement for women with postmenopausal vaginal atrophy.[43,44] Estring has
demonstrated a decreased recurrence of urinary tract infections in
postmenopausal women and a significant maturing effect on vaginal and urethral
mucosal cells, decreasing the urogenital symptoms of postmenopausal women.[45]
Another alternative to local estrogen replacement is the first-available 25-μg 17-beta-estradiol vaginal tablet (Vagifem). A recent study comparing
Vagifem tablets to 1.25-mg conjugated equine estrogen
vaginal cream (Premarin) found both to be equivalent in relieving symptoms of atrophic
vaginitis, with patients who received Vagifem experiencing less endometrial
proliferation or hyperplasia. This study also found that women rated vaginal
tablets more favorably than vaginal cream.[46]
If changes in arousal are also associated with the endocrine changes of
menopause, the option and evaluation of hormone replacement should be
discussed. Some women may experience discomfort with penetration around the
vaginal entrance and can learn to relax the pubococcygeus muscles with
Kegel exercises.[36,47,48] Women who have lost vaginal depth or caliber as a
result of pelvic surgery, radiation therapy, or graft-versus-host disease may
also benefit from a program of inserting vaginal dilators of gradually
increasing sizes, and at the same time, learning exercises to better relax the
muscles surrounding the vaginal entrance.[36,49] Some women may also benefit, at
least in the short term after cancer treatment, from lubricant or anesthetic
gels to prevent pain in tender, dry vulvar areas.[50] The FDA approved a nonpharmaceutical device to aid sexual arousal in women. The EROS
clitoral therapy device (EROS-CTD) creates a gentle suction over the clitoris
to increase blood flow and sensation. This device is only available
by prescription and is clinically indicated for the treatment of female sexual
dysfunction. It is expected to be particularly effective in postmenopausal
women, women who have had hysterectomies, and those women who have
surgically induced menopause.[51] The efficacy of EROS therapy has been supported by several small pilot studies,[52-54] one of which specifically examined its efficacy in alleviating the symptoms of sexual dysfunction among women with a history of irradiated cervical cancer.[53] Three months posttherapy, this study found statistically significant improvements in all domains evaluated, which included increased sexual desire, arousal, lubrication, orgasm, sexual satisfaction, and reduced pain. Additionally, follow-up gynecological examinations revealed improved vaginal elasticity, mucosal color, and moisture and decreased bleeding and ulceration. Randomized controlled trials are warranted to fully assess the benefits of EROS therapy.
More specific information for the evaluation and treatment of female sexual
dysfunction, including painful intercourse (i.e., dyspareunia), vaginismus, inhibited
orgasm, and sexual arousal and desire disorders, is available in other
resources.[37,47,55,56]
For both men and women, a persistent and complex sexual problem is loss of
desire for sex after cancer treatment. In men who have not had prostate cancer
and have clinically low levels of serum testosterone, replacement by injection
or patch is often effective in restoring normal sexual function. Testosterone
replacement tends to have little effect, however, if given to a man whose own
hormone levels fall within the normal range. Safety, dosage, and delivery
systems for androgen replacement in women need to be studied. Media reports
have advocated widespread androgen supplementation for women with ovarian
failure,[57] yet little is known about the minimum levels of androgens
necessary for female sexual function. In a crossover study of
transdermal testosterone in premenopausal but otherwise healthy women who had impaired sexual function
after oophorectomy and hysterectomy, subjects receiving 300 μg of testosterone
per day reported increases in frequency of sexual activity and pleasure.[58]
Mood and general well-being also improved during treatment. Two studies have examined the safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women who did not have breast cancer or gynecologic cancer.[59,60] Data from both of these randomized placebo-controlled trials found that after 24 weeks, women receiving a 300-µg/d testosterone patch had significantly greater increases from baseline in sexual desire and frequency of satisfying sexual activity. For women who have
breast cancer, the safety of giving androgens is unknown. Serum androgens can
be aromatized to estrogen. Evidence from studies of women who underwent
oophorectomy at young ages, showing a reduced long-term risk of breast cancer,
may indicate that androgens are a risk factor.[61] Another troubling line of
evidence comes from epidemiologic studies suggesting that high androgen levels
are present in a subgroup of young women who develop premenopausal breast
cancer.[62]
Because loss of desire often is multifactorial, an approach that includes
psychological assessment and treatment is usually optimal. An experienced
mental health professional can rule out a mood disorder as a factor in loss of
desire and can explore the interactions of factors such as changes in
relationship dynamics, loss of physical well-being, changes in sexual
self-concept, and negative body image. The effects of prescription medications,
chemical dependency, or hormonal abnormalities can be recognized and targeted
for change. Unfortunately, there is no true aphrodisiac medication that can
restore sexual desire in the presence of a normal hormonal environment.
In general, a variety of treatment modalities are available for sexual
dysfunction after cancer. For many problems, providing information and
suggestions for behavior change in a self-help format may be sufficient.
Education can be provided via books,[36] pamphlets,[3,4] CD-ROMs, videos, peer counselors,[63] or
Internet interactions. For men and women with more complex and severe
problems, professional intervention will be more effective. Future research
needs to explore which treatment components are most effective with particular
groups of patients. Sexual counseling can be provided for individuals,
couples, or groups. The effectiveness of these different formats has not been
compared for people with cancer. It is also not known whether brief counseling
can enhance the impact of medical treatments, such as those used to overcome
erectile dysfunction or dyspareunia.
There is limited research about the impact of support groups on sexual outcomes for men with prostate cancer. It is likely that associations between better outcomes and participation in support groups reflect baseline sociographic and clinical differences between those who participate in support groups and those who do not.[64]
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Fertility Issues
Adjuvant radiation therapy and/or chemotherapy introduce higher risks of
infertility in the treatment of cancer. Sterility from these therapies may be
temporary or permanent. The occurrence of this toxicity is related to a number
of factors including the individual’s gender, age at the time of treatment,
type of therapeutic agent, radiation field, total dose, single versus multiple agents, and
length of time since treatment.
When treatment-related or disease-related dysfunction is a possibility, every effort should be made to provide adequate information and education on reproduction and fertility. Conveying such information can be complicated, especially in younger pediatric cancer patients. Children may be too young to comprehend the implications of treatment on fertility. Additionally, in some instances, parents may decide to shelter children from such discussions.[1] Existing literature suggests that only about half of men and women of child-bearing age receive the information they need from their health care providers about cancer-related infertility at the time of diagnosis and treatment planning.[2] This lack of information is one of the most common reasons men give for failing to bank sperm.[2] To address this issue, a computerized interactive educational tool for patients, families, and physicians called Banking on Fatherhood after Cancer is under development and will be viewable on CD-ROM or over the Internet.[2]
Chemotherapy
With regard to chemotherapy, the extent of damage to a patient's fertility depends on the agent administered, the doses received, and the patient's age at the time of treatment. Age is an important factor, and the
possibility of gonadal recovery improves with the length of time off
chemotherapy. The germinal epithelium of the adult testis is more susceptible
to damage than that of the prepubertal testis.[3] The evidence to date
(largely from adjuvant studies) suggests that patients older than 35 to 40
years are most susceptible to the ovarian effects of chemotherapy. The
ovaries of younger women can tolerate greater doses.[4] Predicting the outcome
for any individual patient is difficult, as the course of ovarian functioning
following chemotherapy is variable.[3] Relative risk of ovarian failure and
testicular damage from cytotoxic agents has been studied, and the alkylating
agents have subsequently been shown to be damaging to fertility.
The following agents have been shown to be gonadotoxic: busulfan,
melphalan, cyclophosphamide, nitrosoureas, cisplatin, chlorambucil, mustine,
carmustine, lomustine, cytarabine, ifosfamide, and procarbazine.[3,5-8] In addition to these alkylating agents, vinblastine, cytarabine, cisplatinum, and procarbazine have also been reported to be gonadotoxic in male and female patients.[9] Chemotherapy regimens for the treatment of non-Hodgkin lymphoma are generally
less gonadotoxic than those used for Hodgkin lymphoma.[3] The effects of
chemotherapy on testicular function have also been widely studied in patients
with testicular cancer. One review reported that more than half of the patients with testicular germ cell cancer showed impaired spermatogenesis
before undergoing cytotoxic treatment. Permanent infertility is ultimately
defined by dose of cisplatin in these patients. At doses lower than 400 mg/m2,
long-term effects on endocrine function and sperm production are unlikely to
occur. Higher doses would be expected to cause long-term endocrine-gonadal
dysfunction.[10]
Although chemotherapy causes ovarian damage, there appears to be no risk of toxicity to future offspring of women treated with these agents before pregnancy.[9]
Radiation
When the testes are exposed to radiation, sperm count begins to decrease and,
depending on the dosage, temporary or permanent sterility may result.[4]
Men who receive radiation to the abdominal or pelvic region may still regain
partial or full sperm production depending on the amount of injury to the
testes. Unlike the germinal epithelium, Leydig cell function may be more prone
to damage from irradiation in prepubertal life than in adulthood.[3] Testicular radiation with doses higher than 20 Gy is associated with Leydig cell dysfunction in prepubertal boys, while Leydig cell function is usually preserved with doses of as much as 30 Gy in sexually mature males.[11] Exposing
the testes to ionizing radiation at a dose lower than 6 Gy causes disturbances of
spermatogenesis and altered spermatocytes with recovery periods dependent on
dose;[4] doses higher than 6 Gy cause permanent infertility by killing off all stem
cells.[12] For patients with testicular germ cell cancer, using modern
radiation techniques (radiation doses to the para-aortic field <30 Gy) and
testis shielding providing testis scatter radiation (<30 Gy), radiation-induced
impairment of fertility is very unlikely.[10] Sperm counts are typically lowest at 4 to 6 months posttreatment; return to pretreatment levels usually occurs in 10 to 24 months, with longer periods required for recovery after higher doses.[9] Total-body irradiation (TBI) as a conditioning regimen for stem cell transplantation causes permanent gonadal failure in approximately 80% of men.[13] For men, gonadal toxicity can be
evidenced by the following three measurements: testicular biopsy, serum hormone
assays (levels), and semen analysis. When male infertility is the result of
abnormal hormone production, the use of hormone manipulation may lead to the
return of sperm production.[14]
For women, a dose of 5 Gy to 20 Gy administered to the ovary is sufficient to
completely impair gonadal function regardless of the patient’s age; a dose of
30 Gy provokes premature menopause in 60% of women younger than 26 years.[15] Women who are older than 40 years when undergoing treatment have a smaller pool of remaining oocytes and require only 5 to 6 Gy to produce permanent ovarian failure. TBI, as when used before stem cell transplantation, is associated with more than 90% permanent gonadal failure in women overall and an incidence of pregnancy less than 3%.[9] The outlook for recovery of ovarian function before puberty is more favorable, particularly if radiation is delivered in several fractions.[13] Measurement of gonadal toxicity in women is more difficult to assess
due to the relative inaccessibility of the ovary to biopsy (which would require
laparoscopy). Therefore, menstrual and reproductive history, measurements of
serum hormone levels, and clinical evidence of ovarian function are the
criteria most commonly used to determine ovarian failure. Several authors
provide reviews of gonadal dysfunction in patients receiving chemotherapy [14]
and the effect of cancer therapy on gonadal function.[4]
Preventive Strategies
For women, studies [16] have shown that movement of the ovaries out of the
field of radiation (ovariopexy), either laterally, toward the iliac crest, or
behind the uterus may help preserve fertility when high doses of radiation
therapy are being applied. By relocating the ovaries laterally it is possible
to shield them during radiation of the para-aortic and femoral lymph nodes.[4]
Pelvic radiation, however, still provokes an irradiation of the ovary of 5% to 10%, even if transposed outside the irradiation area.[15] Similar prevention
strategies are available for men. When possible, lead shields are used to
protect the testes.[4]
Procreative Alternatives
When feasible and relative to the necessity of treatment, oncology
professionals should discuss reproductive cell and tissue banking with
patients, referring to a reproductive endocrinologist before chemotherapy
and/or radiation. Men can store sperm from semen ejaculate, epididymal
aspirate, testicular aspirate, and testicular biopsy.[17-20] Women can store
ovarian tissue, ovarian follicles, and embryos.[21,22] In oocyte
cryopreservation, which is still experimental,[23] reproductive cells/tissue
are cryopreserved for future use in artificial insemination for patients who
wish to protect their reproductive capacity. One published case report describes a live birth after in vitro fertilization of thawed cryopreserved ovarian cortical tissue into the ovaries of a 28-year-old woman who experienced ovarian failure secondary to high-dose chemotherapy for non-Hodgkin lymphoma.[24] For this case, ovarian tissue (containing many primordial follicles) was harvested after administration of a second-line conventional therapy regimen and before treatment with high-dose chemotherapy. Freezing oocytes has also had some success but with significant limitations and only a small number of reported pregnancies. Overall current survival rates for the freeze-thaw process range from 15% to 43%, with approximately 45% fertilization rates but only 1% to 2% clinical pregnancy rates.[25] Reviews [15,25,26] of indications for
cryopreservation of ovarian tissue and current reproductive-assisted
technologies are available.
These options may not be appropriate for all patients. Counseling is an
important part of the decision-making process for patients. Thinking through
these decisions at a time when patients are struggling with issues of life and
potential death are often difficult. Patients need to consider costs, stress,
time, emotions, and potential inclusion of another individual in the pregnancy
process (i.e., a surrogate). For many patients, the financial costs associated
with in vitro fertilization and subsequent embryo cryopreservation is cost
prohibitive. Consideration also needs to be given to the current rate of
failure for in vitro fertilization procedures and the potential adverse effect
of malignancy on sperm parameters.[23] A retrospective analysis, with a
limited sample size, reported that the oocytes from patients with malignant
disorders were of a poorer quality and exhibited a significantly impaired
fertilization rate compared with age-matched controls.[23] Importantly, data on
the outcome of pregnancies in cancer survivors [27] have not shown any increase in genetically mediated
birth defects, birth-weight effects, and sex ratios. Based on the evidence
thus far, individuals treated with cytotoxic chemotherapy who remain fertile
are not at an increased risk of having children with genetic abnormalities.[3]
For all patients who wish to be parents and who have permanent infertility,
adoption should be presented as a choice.
Men who are treated with sterilizing chemotherapy may have semen cryopreserved, yet utilization remains low.[28] In a 15-year study of 776 men with a variety of malignancies, the cumulative rate of using the cryopreserved semen for assisted conception was less than 10% up to 8 years. Younger age at cryopreservation and a diagnosis of testicular cancer were associated with lower utilization.[29] Despite poor postthawing sperm survival rates, intracytoplasmic sperm injection (ICSI) offers the possibility of a pregnancy even if only a single motile sperm is present after thawing.[30] Cryopreservation of sperm should be recommended even to oncological patients younger than 15 years (provided these patients can produce a semen sample), as overall success rates (defined as the observation of at least a single motile sperm after the thawing procedure) have been found to be similar to those observed in adults.[31] For men who experience retrograde ejaculation after treatment and remain
fertile, it is often possible to retrieve live sperm cells. An infertility
specialist can retrieve sperm cells from the testicles and from urine. Testis
sperm extraction incorporates the removal of testicular parenchyma with
processing and isolation of individual sperm cells. This allows for ICSI in azoospermic men. In a retrospective
study, 15 of 23 men who were azoospermic after receiving chemotherapy had
retrievable testis sperm leading to successful fertilization. Pregnancies occurred in 31% of cycles. Future research is needed to address whether the offspring produced after ICSI techniques are at increased risk of genetic or congenital malformation.[32] Medication can
sometimes be used to stimulate the remaining nerves around the prostate and
seminal vesicles to convert a retrograde ejaculation to an antegrade
ejaculation. In the United States, ephedrine sulfate is most often used; in
Europe, imipramine has also been used. Pharmacologic agents can also be used
to induce an ejaculation (i.e., intrathecal neostigmine or subcutaneous
physostigmine). When medication does not work, several other techniques are
available and may be recommended, including vibratory stimulation,
electroejaculation, direct aspiration of fluid from the vas deferens, perineal
needle stimulation, and hypogastric-nerve stimulation. Further review of these
treatments and information regarding treatment of infertility and assisted reproductive technology is available.[12,33]
Fertility outcomes after therapy of common cancer types (breast cancer, leukemia and lymphoma, cervical cancer, ovarian cancer, endometrial cancer, and testicular cancer) are available in a published review.[9]
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