INTRODUCTION — Sexual dysfunction is one of the most common and distressing side effects of treatment among female cancer survivors [1]. All forms of cancer treatment have the potential to negatively affect physical sexual function in females, including sexual desire, arousal, orgasm, and pain. Additionally, sexual dysfunction can impair body image, lower self-esteem and sexual satisfaction, and result in psychological distress and decreased quality of life [2,3].
Despite the prevalence of sexual dysfunction related to cancer therapy, the majority of female cancer survivors do not always receive necessary information, support, or treatment for these conditions. Clinicians may efficiently and easily identify patients with sexual dysfunction using validated tools and ubiquity-style inquiry and statements. Guided by a multidisciplinary biopsychosocial model (figure 1), clinicians can also comfortably and thoroughly inquire, assess, and refer if treatment is beyond their expertise [4]. Finally, sexual rehabilitation should encompass both physical and psychosocial aspects of function that have been disrupted in order to maximize the potential for both short- and long-term sexual recovery.
An overview of the epidemiology, etiologies, evaluation, and management of sexual dysfunction in female cancer survivors is discussed in this topic. Sexual dysfunction in other cancer survivors and patient populations are discussed separately.
●(See "Overview of sexual dysfunction in male cancer survivors".)
●(See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Surveillance'.)
●(See "Overview of approach to lung cancer survivors", section on 'Sexual dysfunction'.)
●(See "Overview of psychosocial issues in the adult cancer survivor".)
●(See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation".)
●(See "Overview of sexual dysfunction in females: Management".)
●(See "Epidemiology and etiologies of male sexual dysfunction".)
●(See "Sexual dysfunction in older adults".)
●(See "Sexuality in palliative care".)
EPIDEMIOLOGY — A majority of female cancer survivors endorse at least one distressing symptom related to sexual dysfunction, but few feel prepared to deal with these changes. The type and incidence of specific sexual dysfunction may differ based on the underlying malignancy. Dyspareunia (ie, pain associated with attempted vaginal intercourse) is the most common sexual complaint for female cancer survivors [5].
Over half of female patients treated for breast and genitourinary cancers report long-term negative changes in sexual function. Similarly, among female patients treated for gynecologic cancers, a majority (up to 90 percent) report significant sexual dysfunction [6]. Additional populations of female cancer survivors similarly face high rates of treatment-related sexual dysfunction but are frequently overlooked, such as those with hematologic malignancies treated with hematopoietic cell transplantation [7,8]; female survivors of head and neck cancer; and those with genetic predispositions to malignancy.
●Breast, gynecologic and rectal cancer – The rate of dyspareunia is estimated at 45 percent or greater among survivors of breast cancer and survivors of either gynecologic or rectal cancer treated with radiation therapy [9,10]. Among females with cervical cancer, the rate of dyspareunia ranges between 12 to 58 percent, and is often attributed to estrogen deficiency and structural tissue changes related to cancer therapy [11,12]. (See "Female sexual pain: Differential diagnosis".)
●Hematologic malignancies (treated with hematopoietic cell transplantation) – Females with hematologic malignancies who undergo hematopoietic cell transplantation are at risk for severe mucosal diseases, such as vulvovaginal graft-versus-host disease (GVHD) [13] and lichen sclerosis [14]. Both GVHD and lichen sclerosis are painful conditions that are often either misdiagnosed or go undiagnosed. (See 'Graft-versus-host disease' below and "Female sexual pain: Differential diagnosis", section on 'Vulvar dystrophies and dermatoses'.)
●Head and neck cancers – For females treated for head and neck cancers, over 35 percent report loss of sexual interest and enjoyment [15]. This is most likely related to a combination of factors, including chemotherapy-induced neuropathy, changes in oral sensation (eg, xerostomia) or odor, changes in body image due to surgery, and psychological distress such as anxiety or depression. (See "Overview of approach to long-term survivors of head and neck cancer", section on 'Sexual dysfunction'.)
●Genetic disorders – Finally, female patients at high risk for cancer due to either genetic germline pathogenic variants or familial cancer predisposition often undergo prophylactic surgeries to reduce the risk of breast and/or ovarian cancers, such as mastectomies or bilateral oophorectomies. This population also reports high rates of negative sexual sequelae [16]. However, these individuals often receive little attention or preparation for potential sexual problems because they may not have had a cancer diagnosis before undergoing such interventions. (See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes" and "Cancer risks and management of BRCA1/2 carriers without cancer" and "Overview of hereditary breast and ovarian cancer syndromes associated with genes other than BRCA1/2".)
OVERVIEW OF THE BIOPSYCHOSOCIAL MODEL — Sexual dysfunction in female cancer survivors can be impacted by biological, psychological, interpersonal, and sociocultural factors, otherwise known as the biopsychosocial model (figure 1) [4,17]. Guided by this multidisciplinary model, clinicians can also comfortably and thoroughly assess female cancer survivors for sexual dysfunction; offer specific therapeutic interventions, medical management, and education; and refer them for sexual counseling and/or rehabilitation if treatment is beyond their expertise.
●Biological factors – Biological factors that can impact sexual dysfunction include hormonal changes (eg, due to menopause or endocrine therapy) or anatomic changes to genitalia secondary to therapy that can interfere with sexual response.
●Psychological factors – Psychological factors include possible mood disorders such as depression or anxiety (which can often be comorbid in cancer survivors) or critical self-evaluation during sexual intercourse.
●Interpersonal factors – Interpersonal factors include general satisfaction for the relationship and communication with the patient's partner, which can impact sexual satisfaction.
●Sociocultural factors – Sociocultural factors that can impact a patient's attitude towards sexual health include menopause, age, religion, culture, and other social values.
CAUSES OF SEXUAL DYSFUNCTION — Sexual health is a multidimensional construct that goes beyond intercourse to include intimacy, body image, desire, arousal, orgasm, and satisfaction. Among female cancer survivors, common causes that impact sexual health include both primary therapies (eg, surgery, chemotherapy, radiation therapy [RT], endocrine therapy), secondary etiologies related to cancer treatment, and psychological distress.
Cancer therapy
Surgery — Surgical management, especially in the treatment of breast, gynecologic, bladder, and rectal cancer, often results in anatomic, sensory, and endocrinologic changes that affect sexual function. Examples of such as surgical interventions and their associated impact on sexual dysfunction include the following:
●Mastectomy or lumpectomy – Mastectomy or lumpectomy can alter breast and nipple anatomy, as well as sensation, in female patients with breast cancer. Although most patients undergo breast-conserving and reconstructive surgeries, skin- and nipple-sparing procedures do not preserve sensation. Since nipple sensation and stimulation often plays a central role in sexual arousal, total loss of breast sensation can have a significant negative impact on sexual function. In addition, lymphedema may result from axillary, pelvic, or inguinal lymph node resection, which can result in psychological distress and reduced quality of life. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Psychological morbidity' and "Overview of long-term complications of therapy in breast cancer survivors and patterns of relapse", section on 'Sexual dysfunction'.)
●Hysterectomy – Hysterectomy alone has not been associated with changes in sexual function, based on data from patients with benign disease. However, in patients with cervical cancer, the combination of hysterectomy and RT can lead to changes in the length or caliber of the vagina (eg, vaginal stenosis) as well as decreased vaginal lubrication and elasticity. These changes can adversely affect sexual function, overall quality of life, and psychosocial well-being following treatment. (See 'Vaginal stenosis' below and "Management of early-stage cervical cancer", section on 'Sexual dysfunction' and "Hysterectomy for benign indications: Patient-important issues and surgical complications", section on 'Psychosexual issues'.)
●Vulvectomy – In patients with vulvar malignancies treated with simple vulvectomy, surgery is tailored to maintain body image and preserve sexual function. However, in patients treated with radical vulvectomy, the extensive anatomic changes to the perineum can interfere with sexual response and result in significant sexual dysfunction and psychological distress. (see "Vulvar wide local excision, simple vulvectomy, and skinning vulvectomy" and "Radical vulvectomy", section on 'Introduction').
●Oophorectomy – Bilateral oophorectomy in premenopausal females leads to an abrupt and often severe premature menopause, which is associated with hormonal, physical, and psychological consequences that affect sexual well-being [5]. (See "Oophorectomy and ovarian cystectomy" and "Elective oophorectomy or ovarian conservation at the time of hysterectomy", section on 'Sexual dysfunction'.)
●Cystectomy – Cystectomy for treatment of bladder cancer may result in neural injury and/or changes in pelvic anatomy that alter lubrication and reduce vaginal capacity, such as vaginal foreshortening or narrowing [18]. (See "Radical cystectomy".)
●Colorectal resection, surgical ostomies – Surgery for treatment of colorectal cancer can lead to both neural and anatomic changes that result in vaginal dryness and dyspareunia. Female cancer survivors with permanent surgical ostomies also face a range of challenges that affect sexual function and body image; approximately half of female patients with stomas who were sexually active before surgery report not resuming sexual activity postoperatively [19,20]. (See "Ileostomy or colostomy care and complications", section on 'Sex'.)
Chemotherapy — Chemotherapy contributes to sexual dysfunction in female cancer survivors, regardless of age [21], and may affect all domains of sexual function. The most common side effects associated with chemotherapy include dyspareunia and vaginal dryness, which are most likely due to underlying mucosal injury. Examples of other specific side effects include the following:
●Endocrinologic effects – Younger females who undergo abrupt chemotherapy-related menopause are at the highest risk for sexual problems [22]. Chemotherapy may initiate ovarian failure, leading to sudden loss of estrogens. Similarly, endocrine therapy resulting in estrogen deprivation following chemotherapy-induced menopause leads to vaginal dryness and vaginal atrophy, resulting in dyspareunia. (See "Ovarian failure due to anticancer drugs and radiation", section on 'Chemotherapeutic drugs'.)
●Peripheral neuropathy – Peripheral neuropathy is a common side effect with certain chemotherapeutic agents, such as cisplatin, etoposide, taxanes, and vinca alkaloids. Perineal nerves may be affected, leading to numbness, tingling, or neuropathic pain [23]. (See "Overview of neurologic complications of platinum-based chemotherapy" and "Prevention and treatment of chemotherapy-induced peripheral neuropathy".)
●Mucosal changes – Some chemotherapeutic agents, such as pegylated liposomal doxorubicin, may cause vaginal or rectal mucosal toxicity [24].
Radiation therapy — RT for pelvic (ie, cervical, uterine, colon, and rectal) cancers can adversely impact sexual dysfunction due to both acute and long-term effects on the bowel, bladder, and vagina [25].
Common acute effects of RT that may impact sexual function during or immediately after RT include acute radiation injury to the bowels (eg, nausea, vomiting, diarrhea, radiation proctitis), bladder (eg, radiation cystitis) and vagina (eg, vaginal mucositis). (See "Treatment-related toxicity from the use of radiation therapy for gynecologic malignancies", section on 'Gastrointestinal' and "Treatment-related toxicity from the use of radiation therapy for gynecologic malignancies", section on 'Genitourinary system toxicities'.)
Chronic effects of RT that impact sexual function over time include vaginal atrophy, adhesions, and fibrosis. Compounded by the effects of menopause, these changes may lead to decreased tissue elasticity and vaginal stenosis, or the narrowing and shortening of the vaginal canal. Vaginal stenosis may cause dyspareunia and ultimately prevent vaginal penetration [26]. Rarely, patients may experience rectovaginal or vesicovaginal fistulas. (See "Treatment-related toxicity from the use of radiation therapy for gynecologic malignancies", section on 'Vagina' and 'Vaginal stenosis' below.)
Endocrine therapy — In breast cancer patients, treatment with endocrine therapy may lead to vaginal dryness, dyspareunia, and decreased sexual desire [27,28]. As the duration of endocrine therapy has been extended for many female cancer survivors, it is important to recognize that unmanaged sexual side effects of endocrine therapy are one of the most common reasons for early treatment discontinuation [28,29]. This pattern is seen mostly in women treated with aromatase inhibitors and less commonly in those treated with tamoxifen. (See "Adjuvant endocrine and targeted therapy for postmenopausal women with hormone receptor-positive breast cancer", section on 'Sexual dysfunction'.)
Endocrine therapy is used in patients with estrogen receptor-positive breast cancer to lower risk of cancer recurrence, either by blocking estrogen receptors or stopping estrogen production systemically. Since approximately two-thirds of breast cancers are hormone receptor positive, the majority of breast cancer survivors undergo adjuvant hormonal treatment, including aromatase inhibitors and selective estrogen receptor modulators.
Aromatase inhibitors block the peripheral conversion of androgens to estrogen, resulting in profound estrogen deficiency. As a result, these agents have been commonly associated with severe vaginal dryness, dyspareunia, decreased libido, and other forms of sexual dysfunction [27,28].
Tamoxifen is a selective estrogen receptor modulator, which has both estrogen agonist and antagonist effects on different tissues [30]. Data suggest that vaginal dryness is uncommon with tamoxifen, which is more likely to cause vaginal discharge [31]. Randomized trials have also demonstrated that vaginal dryness occurs less frequently with tamoxifen than with aromatase inhibitors [32].
In a study of breast cancer survivors receiving endocrine therapy, over 56 percent of females taking an aromatase inhibitor and 31 percent taking tamoxifen reported dyspareunia [5]. Aromatase inhibitors in particular lead to more severe sexual side effects, including vulvovaginitis and loss of the normal vaginal architecture [33].
Secondary etiologies
Menopause — Symptoms of menopause include hot flashes, body aches, depressed mood, poor sleep, decreased libido, and vaginal dryness. The vasomotor symptoms, body aches, and mood effects seen in patients with menopause are related to fluctuations of estradiol, decreases in inhibin B, and elevation of follicle-stimulating hormone (FSH) [34]. (See "Clinical manifestations and diagnosis of menopause".)
Genitourinary syndrome of menopause (GSM) describes a constellation of vulvovaginal and urinary symptoms associated with estrogen deficiency that can be seen in female survivors of breast, endometrial, uterine, and ovarian or fallopian tube cancers [35]. This syndrome and its management are discussed separately. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Clinical manifestations and diagnosis" and "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment".)
Cancer treatments often exacerbate symptoms of menopause in female cancer survivors [28]. In an observational study of 1089 females with menopausal symptoms, female cancer survivors were more likely than those without a cancer history to be troubled by vasomotor symptoms, including hot flashes and night sweats [36]. Survivors of breast cancer are reported to have an earlier onset of GSM symptoms due to the effects of chemotherapy, radiation, and surgical removal of the ovaries [28,37]. In addition, adjuvant endocrine therapy often worsens hot flashes and genitourinary symptoms [29,38]. (See "Menopausal hot flashes", section on 'Women with breast cancer'.)
Graft-versus-host disease — Female patients who undergo hematopoietic cell transplantation are at risk for graft-versus-host disease (GVHD), a T cell-mediated immune response in which the grafted donor cells react with antigens in the host. Such patients are at risk for developing vaginal GVHD, which can occur within the vulvar skin and vaginal mucosa [13]. Vaginal GVHD is less common than involvement of other organs (such as the skin and gastrointestinal tract), and most cases of chronic vaginal GVHD are mild and asymptomatic. More severe responses include vaginal inflammation, dryness, erosions, fissures, strictures, vaginal stenosis, and complete vaginal obstruction [13,39,40]. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease" and 'Vaginal stenosis' below.)
Vulvodynia — Vulvodynia is defined as a persistent vulvar pain without an identifiable cause and has been present for at least three months [41].
Vulvar pain in female patients receiving cancer therapy was previously classified as vulvodynia (ie, vulvar pain of unknown cause). However, based on consensus terminology developed in 2015 [42], vulvar pain in female patients due to cancer treatments and menopause was subsequently re-classified as vulvar pain caused by a specific disorder (such as chemotherapy, radiation, surgery, and hormonal deficiencies) [41,43-45]. However, female cancer survivors with severe pain inconsistent with vulvovaginal atrophy should also be evaluated for localized, provoked, or generalized vulvodynia [5]. (See "Vulvar pain of unknown cause (vulvodynia): Clinical manifestations and diagnosis".)
Pelvic floor muscle dysfunction (including vaginismus) — Pelvic floor dysfunctions are prevalent in females affected by gynecologic and breast cancers. These symptoms include urinary incontinence, fecal incontinence, and dyspareunia (eg, pain associated with sexual intercourse) [12]. (See "Sexual function in females with pelvic floor and lower urinary tract disorders".)
Dyspareunia may occur before, during, or after vaginal intercourse. This pain is often related to overactive pelvic floor muscle tension that leads to burning pain associated with vaginal intercourse.
Vaginismus describes the involuntary contraction of the muscles at the vaginal entrance in response to attempted penetration, even though sexual desire is present [46]. Secondary vaginismus may occur as a response to painful sexual encounters [5]. Pain may lead to fear of intercourse and avoidance of sexual intimacy [47]. (See "Female sexual pain: Differential diagnosis", section on 'Vaginismus and myofascial pelvic pain syndrome (MPPS)'.)
Urinary or bowel dysfunction — Radiation and surgery can lead to significant gastrointestinal and genitourinary complications such as cystitis, proctitis, fistulas, and anal fissures. Such urinary and bowel dysfunction can impair sexual intimacy and intercourse [48,49]. (See "Approach to the long-term survivor of colorectal cancer", section on 'Sexual dysfunction' and "Female urinary incontinence: Evaluation".)
Other etiologies (fatigue and pain) — Pain and fatigue are often late, debilitating effects of cancer treatment. Since treatment-related sexual function is often a multifactorial problem, pain and fatigue can have a direct impact on sexual function, including loss of desire and arousal. Patients undergoing cancer therapy should be offered supportive resources and education around managing pain and fatigue. (See "Assessment of cancer pain" and "Cancer-related fatigue: Treatment".)
Psychological distress — Psychological distress in female cancer survivors has been associated with significant changes in sexual function, both acute and long-term, and decreased quality of life [3]. (See "Overview of psychosocial issues in the adult cancer survivor".)
Major areas of impact include body image, mood disorders, and relationship factors.
Body image — Cancer therapy can result in body alterations, such as alopecia, surgical ostomies, or mastectomy. The negative impact of such physical alterations on perceived body image and body integrity is frequently acknowledged. In one study, approximately 50 to 75 percent of younger female cancer survivors reported problems with body image, most commonly in the immediate postoperative and treatment period [50].
However, changes in body image and negative sexual self-esteem may be driven by changes that are less obvious, such as loss of sensation, loss of saliva, or premature menopause. Risk factors for treatment-related sexual dysfunction due to problems with body image include premorbid sexual dysfunction [51], negative self-concept [52], depression, relationship discord [52,53], younger age, and lack of partner status [54]. (See "Body dysmorphic disorder: Assessment, diagnosis, and differential diagnosis".)
Depression and antidepressant medication — Depression and associated therapy with antidepressant medication are both important determinants of lower sexual desire. In one study, up to one-third of breast cancer survivors use antidepressant medications after diagnosis to treat depression and/or hot flashes [55]. Antidepressant medications, in particular selective serotonin reuptake inhibitors, are also associated with significant decrease in sexual desire and interference with arousal and orgasm. (See "Sexual dysfunction caused by selective serotonin reuptake inhibitors (SSRIs): Management" and 'Decreased libido and arousal' below.)
Relationship factors — Treatment-related sexual dysfunction in female cancer survivors can also negatively impact and disrupt intimate relationships with their partners. For many couples, it can be difficult to restore relationship intimacy against the backdrop of multiple treatment-related stressors and after a lengthy period of inactivity. Partners may also feel either embarrassed or uncomfortable talking about changes in sexual function, which can lead to complex patterns of intimacy avoidance [56,57]. (See "Overview of sexual dysfunction in females: Management", section on 'Address partner issues'.)
SCREENING AND COUNSELING — Sexual function is often an important factor contributing to quality of life, with a majority (74 percent) of cancer survivors ranking discussion of sexual problems with their oncologist as "important" [58]. As such, screening and counseling on sexual dysfunction in female cancer survivors can occur at any time before, during, or after cancer therapy.
Barriers — Many barriers still exist in the pretreatment and posttreatment setting that prevent adequate screening and counseling on sexual dysfunction [59]. Many of the barriers that hinder discussing sexuality in female cancer survivors are similar to those in other fields of medicine. These barriers can be overcome by early integration of screening and counseling as part of pretreatment evaluation; obtaining information on sexual function during and after treatment using validated questionnaires; and using brief screening tools and ubiquity-style inquiry. (See 'Approaches' below.)
●Pretreatment barriers – Although the prevalence of treatment-related sexual dysfunction is well established, the majority of female patients with cancer do not receive necessary information or support to prepare them for potential sexual changes and side effects related to cancer therapy [2,59]. Initial discussions at the time of cancer diagnosis often prioritize treatment plans and prognosis rather than concerns about sexual dysfunction. As such, we integrate early screening and counseling on sexual dysfunction into the pretreatment evaluation. For example, clinicians may screen for sexual dysfunction while reviewing potential treatment-related toxicities, including impact on sexual function.
●Posttreatment barriers – Although clinicians generally acknowledge the importance of sexual health after cancer, posttreatment sexual function is often not assessed due to a variety of personal and systemic barriers, including lack of comfort with the topic, lack of time, lack of training, and perceived lack of educational resources as barriers to inquiry [58]. Female cancer survivors may be less likely to initiate discussion about sexual function with their medical providers during or after treatment because they may be uncomfortable, embarrassed, or anxious about the topic, or they assume that it not a priority [5].
Approaches — Various approaches exist to screen and counsel female cancer patients for sexual dysfunction in both the pretreatment and posttreatment settings. In addition to the methods discussed below, clinicians can increase their comfort addressing sexuality by developing their own techniques and incorporating various tools into their routine patient interactions. By acknowledging their own discomfort or embarrassment associated with sexual topics, clinicians may diffuse barriers between them and their patients [60]. Additionally, patients should also be reassured that any discussion about sexual function and habits are always confidential.
Ubiquity-style inquiry — When screening female cancer patients for sexual dysfunction, we suggest ubiquity-style inquiry over longer, more intensive patient-reported outcomes. Studies indicate that female patients with cancer want their oncologist to initiate a discussion about sexual function [58]. Providers should be aware of how to initiate straightforward inquiry about sexual health and have access to clinical screening tools that are brief and easy to interpret.
First, we advise use of a brief ubiquity-style inquiry that acknowledges, validates, and asks about the problem, such as, "Many patients who have gone through similar cancer treatment notice changes in sexual function or vaginal health. What has been your experience been like?" [61,62]. This statement also conveys to the patient that sexual function is an important component of well-being that is open for discussion during the visit. Although there are limited data comparing ubiquity-style inquiry with longer, patient-reported outcome questionnaires, we prefer this approach due to the time constraints of clinical visits. (See 'Patient-reported outcome questionnaires' below.)
Brief screening tools — In addition to ubiquity-style inquiry, clinicians may also use a brief screening tool that can serve as a guide for clinical inquiry, such as The Sexual Symptom Checklist for Female Patients After Cancer (form 1) [63]. This screening tool takes approximately three minutes to use. It can be employed either as a self-report checklist, as a guide for clinical conversation about treatment-related sexual problems, and to serially track improvements in patient symptoms. It is also intended for use regardless of partner status, sexual orientation, or current level of sexual activity. There are limited studies comparing these brief screening tools with longer, patient-reported outcome questionnaires, and further data are necessary.
Patient-reported outcome questionnaires — Patient-reported outcome questionnaires can also be a useful resource in opening a discussion on sexual function. However, such tools may be too time-intensive to incorporate into routine clinical practice. Questionnaires can be utilized longitudinally over the course of treatment and survivorship care. Specific tools include the Female Sexual Function Index (FSFI) and the National Institute of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction (PROMIS SexFS).
●Female Sexual Function Index – The FSFI is a validated 19-item self-report questionnaire addressing sexual arousal, orgasm, satisfaction, and pain [64]. However, standardized measures (such as the FSFI) may be too lengthy and time- and labor-intensive for routine use in a busy clinical practice, while also yielding a surplus of information for the provider to address. (See "Female orgasmic disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis", section on 'Quantitative measurements and rating scales'.)
●PROMIS SexFS – The PROMIS SexFS tools also address various sexual functions and may be more inclusive of different sexual orientations [65]. However, these and almost all validated measures that assess female sexual function after cancer are premised on the patient being currently sexually active. This is problematic for many female cancer survivors who have sexual or vaginal health concerns but have ceased having regular sexual activity due to these symptoms.
The use of PROMIS tools to evaluate other health-related quality of life domains are discussed separately. (See "Evaluation of health-related quality of life (HRQL) in patients with a serious life-threatening illness", section on 'PROMIS'.)
There are limited data comparing these longer, comprehensive patient-reported outcome questionnaires with other ubiquity style inquiry or other brief screening tools, and further studies are necessary. (See 'Ubiquity-style inquiry' above and 'Brief screening tools' above.)
DIAGNOSTIC EVALUATION
Medical history — A complete medical and gynecologic history should be obtained in female cancer survivors, using a similar approach to females in the general population with sexual dysfunction. This is discussed in more detail separately. (See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation", section on 'Medical history'.)
Additionally, clinicians should obtain the patient's complete cancer treatment history, including prior surgery, radiation therapy (RT), and systemic agents. Reviewing operative notes and radiation summary reports may provide additional insight into the etiology of sexual dysfunction in female cancer survivors, especially in regard to sexual pain [43]. Current and prior systemic treatments (eg, chemotherapy, targeted therapy, endocrine therapy, and immunotherapy) should be reviewed because such therapy may adversely impact sexual function, menopausal status, psychological state, and overall well-being to varying degrees. The patient's medications should also be reviewed for adjunct treatments such as antidepressant, pain, or neuropathic medications, among others. (See 'Cancer therapy' above.)
Sexual history — Eliciting a sexual history (including a history of early life or sexual trauma) is an essential component in the evaluation of female cancer survivors (table 1). In contrast with other treatment-related side effects, inquiries about sexual function is not generally incorporated into the routine review of systems, even though this issue can significantly impair quality of life for years after treatment ends. Despite the prevalence of sexual dysfunction and the importance of these issues to patients and their partners, most survivors are not asked about concerns related to sexuality. (See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation", section on 'Medical history'.)
In female cancer survivors, clinicians should also focus on the following symptoms. These symptoms, which are consistent with questions from the Sexual Symptom Checklist for Female Patients After Cancer (form 1), include:
●Persistent lack of sexual desire that is bothersome to the patient
●Decreased or absence of genital arousal or sensation
●Changes with, or inability to orgasm
●Pain or discomfort associated with sexual intercourse (eg dyspareunia)
●Psychosocial factors affecting sexual function (eg, anxiety, depression, critical self-evaluation during sexual intercourse) (see 'Overview of the biopsychosocial model' above)
Physical examination — In female cancer survivors with sexual dysfunction, a systematic physical examination ensures a thorough evaluation and can identify potential symptom etiologies related to prior cancer therapy.
General physical examination — The presence of general physical changes from cancer treatment should also be noted. Examples include:
●Mood and affect (to assess for mood disorders)
●Alopecia or the presence of a scalp prosthetic (eg, wig)
●Oral cavity examination (such as mucositis, salivary changes, oral odor)
●Postoperative findings (such as mastectomy or lumpectomy scars, enteral feeding tubes, surgical ostomies, or limb amputations)
●Skin exam to assess for graft-versus-host disease in patients receiving hematopoietic cell transplant (see 'Graft-versus-host disease' above)
●Evaluation for the presence of masses or other physical examination findings concerning for recurrent or metastatic disease (eg, new bony or musculoskeletal pain in patients with a history of breast cancer)
Other organ systems — Further physical examination should be focused on previously treated areas and/or specific symptoms as follows:
Breast examination — Patients with a previous history of breast cancer treatment or symptoms affecting the breasts, a thorough breast examination involves the following (see "Clinical manifestations, differential diagnosis, and clinical evaluation of a palpable breast mass", section on 'Physical examination'):
●Systematic inspection and palpation of breast tissue, nipples, and axilla, including axillary lymph nodes.
●The breasts should be examined for specific findings that may affect sexual function, including tenderness, fullness, induration, lesions, masses, tightening, hyperesthesia, discoloration, and asymmetry of the breasts.
●The nipples may have discharge or ulceration, or may appear flattened, reconstructed, or surgically absent.
●The axilla and upper extremities should be examined for edema, masses, discoloration, and skin changes [66].
Pelvic examination — For patients with prior therapy to pelvic organs and/or symptoms of sexual dysfunction affecting the genitals and/or pelvis, a pelvic examination involves both external inspection (figure 2) followed by internal vaginal examination. Clinicians may involve the patient in the pelvic exam to increase the patient's sense of autonomy and comfort. For example, the clinician can request the patient to retract the clitoral hood or to hold a handheld mirror to the vulvovaginal region and identify painful areas. (See "The gynecologic history and pelvic examination", section on 'Pelvic examination' and "Surgical female urogenital anatomy", section on 'Lower genital tract'.)
●External inspection – External inspection includes palpation of the groin, mons pubis, and vulva, including the vulvar vestibule. Evaluation of the vulva may reveal areas of masses, sensitivity, irritation, erosion, fissuring, ulceration, or loss of anatomic structure, such as vulvovaginal atrophy.
A cotton swab test is used to assess for allodynia of the vestibule, which can contribute to dyspareunia. This test involves lightly pressing a cotton swab on various areas in the vestibule in a clocklike distribution to evaluate localized pain or burning. The vulvar vestibule is particularly sensitive to hormonal deficiency, which can occur with cancer treatments, including oophorectomy, chemotherapy, RT, and endocrine therapy, especially aromatase inhibitors.
The cotton swab may also be used to assess vulvar and clitoral sensation in determining pain or desensitization localized to a particular nerve distribution. Surgery and RT for pelvic cancers may result in injury and lead to nerve-related pain involving the pudendal, genitofemoral, obturator, ilioinguinal, or iliohypogastric nerves [43].
●Internal pelvic examination – An internal pelvic examination should assess for vaginal narrowing, elasticity, tenderness, and length. A digital examination with one lubricated gloved finger may be useful prior to utilizing a speculum. Speculum examination allows the clinician to assess vaginal length, capacity, and health of the vaginal epithelium. Pelvic radiation may lead to vaginal epithelial thinning and pallor, vaginal telangiectasia, loss of elasticity, lack of lubrication leading to dryness, and vaginal shortening or stenosis. The examination should also evaluate for tumors or masses concerning for recurrent or metastatic disease.
Other tests
Vaginitis and STDs — Patients should also be evaluated for vaginitis and other sexually transmitted diseases (STDs) as a potential etiology of symptoms related to sexual dysfunction. These topics are discussed separately. (See "Vaginal discharge (vaginitis): Initial evaluation" and "Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents", section on 'Females with urogenital symptoms' and "Clinical manifestations and diagnosis of Chlamydia trachomatis infections", section on 'Clinical syndromes in females'.)
Imaging — Further spinal, vulvar and/or pelvic imaging such using ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) may be necessary based upon initial history and physical examination. As one example, exam findings concerning for pudendal neuralgia or spinal pathology corresponding to the S2-4 regions should be evaluated using an MRI of the lumbosacral spine. As another example, a suspicious pelvic mass concerning for malignancy could be initially evaluated using transvaginal and transabdominal pelvic ultrasound; MRI of the pelvis could subsequently be obtained (ie, for surgical evaluation).
Diagnostic nerve blocks — In female cancer survivors experiencing pain involving the genitals and/or pelvis, diagnostic nerve blocks may aid in the diagnosis and treatment of nerve entrapments, which can occur due to radiation-induced fibrosis. This and other complex diagnostic or invasive testing should be obtained in consultation with a multidisciplinary team including interventional radiology, anesthesiology, gynecologists, urologists, physical medicine and rehabilitation (PM&R) specialists, pelvic floor physical therapists, sex therapists, and mental health professionals. (See 'Treatment team and referral' below.)
MANAGEMENT — The majority of female cancer survivors report feeling unprepared to deal with sexual side effects of treatment. As the first step in managing treatment-related sexual dysfunction, it is helpful to educate patients about the biopsychosocial model (figure 1), including a brief explanation of how cancer treatment can disrupt various domains of sexual function. (See 'Overview of the biopsychosocial model' above.)
For example, postmenopausal breast cancer survivors may not be aware that urinary symptoms (eg, genitourinary syndrome of menopause [GSM]) can be driven biologically by endocrine therapy due to associated estrogen deficiency. This brief educational overview also conveys a message that sexual recovery is possible, which impacts the interpersonal, psychological, and sociocultural domains. Cancer survivors often feel additionally burdened by social stigmas attached to sexual dysfunction. It can be a relief to survivors when their clinicians offer validation that unmanaged sexual dysfunction does not have to be the "price to pay" for becoming a cancer survivor. (See 'Menopause' above and "Genitourinary syndrome of menopause (vulvovaginal atrophy): Clinical manifestations and diagnosis".)
Dyspareunia — Dyspareunia (ie, pain associated with attempted vaginal intercourse) is the most common sexual complaint for female cancer survivors [5]. Female patients receiving therapies for breast, endometrial, uterine or ovarian/fallopian tube cancers that decrease levels of estrogen and androgens may experience dyspareunia, a symptom associated with GSM, due to genitourinary changes such as microabrasions, skin irritation, and atrophy.
A general treatment approach to dyspareunia in female cancer survivors is provided below. Further details of the management of dyspareunia in female survivors of specific cancers are discussed separately.
●(See "Overview of approach to endometrial cancer survivors", section on 'Sexual dysfunction'.)
Initial therapy — Initial treatment for dyspareunia typically includes nonhormonal therapies (ie, personal lubricants and vaginal moisturizers). (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment", section on 'Initial therapy with moisturizers and lubricants'.)
Personal lubricants — Personal lubricants can be used at the time of sexual activity to reduce discomfort and friction associated with sexual intercourse and vaginal penetration. There are three general types of personal lubricants: water-based, silicone-based, and oil-based. Silicone- and oil-based lubricants may last longer than water-based lubricants but should not be used with silicone dilators or other sex aids (eg, silicone vibrators) [67,68]. Data are limited and highly variable for the efficacy of personal lubricants in female cancer survivors. Further details on the use of personal lubricants are discussed separately. (See "Overview of long-term complications of therapy in breast cancer survivors and patterns of relapse", section on 'Sexual dysfunction'.)
Vulvovaginal moisturizers — Vulvovaginal moisturizers and emollients can be used on a more regular basis (independent of sexual activity) to hydrate and maintain moisture in vulvar and vaginal tissues. Vulvovaginal moisturizers are typically inserted or applied about two to three times per week, although they may also be used on a daily basis. Options include vaginal moisturizing creams (eg polycarbophilic moisturizers such as Replens), vaginal pH balanced gels (such as RepHresh), hyaluronic acid suppositories, vitamin E suppositories, and natural oils. Further details on vulvovaginal moisturizers are discussed separately. (See "Overview of approach to endometrial cancer survivors", section on 'Sexual dysfunction' and "Overview of long-term complications of therapy in breast cancer survivors and patterns of relapse", section on 'Sexual dysfunction'.)
Subsequent therapy
Vulvovaginal low-dose estrogens — For select female cancer survivors who experience dyspareunia that is not relieved by nonhormonal therapies, hormonal therapies (eg, vulvovaginal low-dose estrogen therapy) may be offered as subsequent therapy. Low-dose estrogen comes in a variety of forms, including creams, tablets, capsules, and rings (table 2). Further details on available preparations, efficacy, and systemic absorption of these agents are discussed separately. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment", section on 'Preparations: Cream, tablet, capsule, ring'.)
While there may be apprehension about patients with estrogen-sensitive cancers using vulvovaginal estrogen therapy, data indicate that contemporary low-dose vaginal estrogen options do not increase serum estrogen levels above the menopausal range and have not been associated with increased recurrence rates of breast cancer or endometrial stimulation [69-71].
●Low-dose vaginal estrogen therapy is a reasonable option in appropriately screened patients following treatment for endometrial cancer. (See "Overview of approach to endometrial cancer survivors", section on 'Sexual dysfunction' and "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment", section on 'Vaginal estrogen therapy'.)
●However, for patients with breast cancer, its use is individualized based on the type of breast cancer treatment (eg, estrogen receptor modulators versus aromatase inhibitors) and is discussed in detail separately. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment", section on 'Patients with breast cancer'.)
Local low-dose estrogens or estradiol applied to the introitus and/or vagina is considered most effective in management of dyspareunia due to GSM [72]. Although topical estrogen is typically applied intravaginally, females with sexual pain often require application of topical estrogen to the introital area, including the urethra, inner labia minora, vulvar vestibule, and posterior fourchette (figure 2) [43]. Topical estrogen may also prevent vulvovaginal changes when they are initiated soon after oophorectomy or ovarian ablation [73]. When applied consistently, local estrogens may also reverse up to 90 percent of atrophic vulvovaginal changes [43,72].
There are limited data comparing vulvovaginal low-dose estrogen with nonhormonal therapies with female cancer survivors. Although one placebo-controlled randomized trial demonstrated few differences in efficacy between vaginal estrogen tablets and two nonhormonal lubricants/moisturizers in postmenopausal female patients, patients undergoing cancer treatment were excluded from this study [74]. Further details on this trial are discussed separately. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment", section on 'Efficacy'.)
Vaginal laser therapy — Fractional microablative carbon dioxide (CO2) lasers and nonablative photothermal erbium-doped yttrium aluminium garnet (Er:YAG) lasers have been utilized for treatment of vaginal dryness and dyspareunia in female cancer survivors with vaginal atrophy, but the safety and efficacy of this approach remains uncertain. Further data are necessary to determine which type of laser treatment is more effective, the number or frequency of treatments required, patient acceptability, and comparison with other treatment options. This topic is discussed separately. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment", section on 'Laser or radiofrequency devices'.)
One systematic review that included six nonrandomized studies of moderate to poor quality with a total of 163 survivors of breast cancer showed objective and subjective improvement in vaginal atrophy and sexual function lasting up to 12 months [75].
Vaginal stenosis — Vaginal stenosis can occur as a result of pelvic surgery (eg, operative changes from hysterectomy that narrow, shorten, or deviate the vaginal canal), pelvic radiation, and graft-versus-host disease (GVHD) [39,49]. The primary treatments for vaginal stenosis are the application of vaginal dilators and pelvic floor physical therapy.
Vaginal dilators — The goal of treatment with vaginal dilators is to limit the formation of adhesions by gently separating the layers of the vaginal wall. For females who wish to maintain vaginal function after pelvic radiation, vaginal dilators should be utilized approximately two to four weeks after treatment completion. A lubricated dilator is vaginally inserted for a duration of 10 to 20 minutes, three times a week. Vaginal bleeding with dilator use is common, and vaginal lubricants, moisturizers, and local hormone preparations may be useful adjuncts [43].
Unfortunately, adherence with vaginal dilators is low, and female patients often discontinue treatment due to lack of education on its proper use and/or therapeutic success. To optimize the efficacy of vaginal dilators, patients should be referred to a pelvic floor physical therapist who can demonstrate and educate patients on the use of vaginal dilators. For example, patients should be taught that the dilator gradually stretches an atrophic or shortened vagina; retrains the body to gain control of pelvic floor muscles; and reduces involuntary pelvic floor tightening due to anticipatory anxiety.
Among female patients treated with pelvic radiation, the consistent use of dilators in graduated sizes is associated with lower rates of stenosis, in one systematic review [76]. However, limited data from randomized trials demonstrate no improvements in sexual health with vaginal dilation. (See "Treatment-related toxicity from the use of radiation therapy for gynecologic malignancies", section on 'Vaginal stenosis'.)
Pelvic floor physical therapy — Pelvic floor physical therapy (PT) can play an additional and vital therapeutic role in treating vaginal stenosis, in addition to other symptoms such as pelvic pain, dyspareunia, and bowel or bladder incontinence. Pelvic floor physical therapists can help female patients optimize use of vaginal dilators and teach them how to contract and relax pelvic floor muscles and improve muscle flexibility. (See "Myofascial pelvic pain syndrome in females: Pelvic floor physical therapy for management" and "Chronic pelvic pain in adult females: Treatment", section on 'Physical therapy'.)
In addition, pelvic floor PT may be used as preventive strategy in females undergoing cancer treatments who are at risk for developing pelvic floor muscle dysfunction. (See "Overview of approach to endometrial cancer survivors", section on 'Sexual dysfunction'.)
Decreased libido and arousal — Decreased libido and impaired arousal (ie, low desire) are some of most common and distressing side effects of treatment for female cancer survivors. Loss of sexual desire is typically driven by factors that are biological (eg, hormonal deprivation, vaginal dryness, pain) as well as psychological, interpersonal, and sociocultural (eg, negative body image, psychological or relationship distress). Because of the multifactorial nature of low desire, it is particularly important to bring a biopsychosocial approach to the diagnosis and management of these patients (figure 1). (See 'Overview of the biopsychosocial model' above.)
For female cancer survivors, low desire may often be initially ameliorated by treating underlying physical etiologies such as dyspareunia, vaginal dryness, or pelvic pain. For patients whose symptoms of low desire do not improve with treatment of physiologic etiologies, we suggest referral to a mental health provider and/or a sex therapist for behavior-based interventions that focus on mindfulness-based approaches to enhancing desire [77-79]. We also suggest referral for sex therapy or couples-based psychotherapy for female patients who specifically endorse concerns related to body image, psychological concerns, and relationship distress. As the theoretical model of female sexual desire has significantly shifted over the last two decades, there is a growing understanding of the importance of reframing expectations around the spontaneity of desire and, alternatively, emphasizing the responsive nature of desire [80]. Desire may be understood as an experience that can be cultivated through multiple modalities, both behavioral and cognitive. Specific examples include use of novel stimuli, pleasure-focused sensual awareness, intimacy-focused exercises with a partner, and enhancement of nonjudging cognitive awareness. (See "Overview of sexual dysfunction in females: Management", section on 'Hormone therapy' and "Overview of psychosocial issues in the adult cancer survivor".)
Pharmacologic interventions are not effective in treating low desire. As an example, in a randomized phase II trial of 230 female survivors of breast and gynecologic cancer with low baseline sexual desire (based on the Female Sexual Function Index [FSFI]), treatment with bupropion at either 150 mg or 300 mg over a ten-week period did not improve sexual desire compared with placebo (mean change in FSFI desire subscale score from baseline to nine weeks for 150 mg daily 0.02, 95% CI -0.36 to 0.39; for 300 mg daily -0.02, 95% CI -0.40 to 0.36) [81].
In addition, pharmacologic interventions are often not indicated for female cancer survivors who are postmenopausal or experiencing low desire secondary to a general medical condition or the direct, physiologic effects of a substance or medication (eg, selective serotonin reuptake inhibitors). The role of androgen (ie, testosterone) therapy in this setting is also uncertain. Further details on such pharmacologic interventions are discussed separately. (See "Sexual dysfunction caused by selective serotonin reuptake inhibitors (SSRIs): Management" and "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation", section on 'Role of androgens'.)
Anorgasmia — Although often not discussed, female cancer survivors may experience the inability to orgasm (ie, anorgasmia or hypo-orgasmia) due to treatment-related menopausal symptoms [82]. Similar to postmenopausal females, those female patients with vaginal dryness due to cancer therapy typically need increased stimulation to reach orgasm. However, such vaginal dryness can make stimulation uncomfortable or painful, thus resulting in failure to reach climax. Initial therapy with sexual aids (eg, vibrators) can support oxygenated genital blood flow and enhance masturbation, genital stimulation, and arousal. Patients should also be advised to use lubricants with sexual aids; however, silicone-based personal lubricants should not be used with silicone vibrators because silicone surfaces may bond together and compromise the integrity of the vibrator covering. Further details on the treatment of female anorgasmia are discussed separately. (See "Treatment of female orgasmic disorder".)
TREATMENT TEAM AND REFERRAL — When guided by a biopsychosocial understanding (figure 1) of cancer-related female sexual dysfunction, clinicians will be more likely to inquire about sexual health in female cancer survivors if they have appropriate resources and referrals to offer patients. Patients should be provided access to a multidisciplinary treatment team with expertise in the management of sexual dysfunction in cancer survivors, including a gynecologic provider with expertise in managing menopause; a psychosocial (mental health) provider and/or a sex therapist; and a pelvic floor physical therapist who has experience working with cancer survivors.
It is also useful to offer a list of educational resources, websites, and providers, which can be made available to both patients and their partners. (See "Overview of sexual dysfunction in females: Management", section on 'Resources for clinicians and patients'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Female sexual dysfunction".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Sex problems in females (The Basics)" and "Patient education: Sex as you get older (The Basics)" and "Patient education: Dyspareunia (painful sex) (The Basics)")
●Beyond the Basics topics (see "Patient education: Sexual problems in females (Beyond the Basics)" and "Patient education: Pelvic floor muscle exercises (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Epidemiology of sexual dysfunction in female cancer survivors – A majority of female cancer survivors endorse symptoms related to sexual dysfunction, but few feel prepared to deal with these changes. While sexual dysfunction is most commonly seen in those with breast, genitourinary, and rectal cancers, it can also be seen in female survivors of other frequently overlooked malignancies such as hematologic malignancies (treated with hematopoietic cell transplantation) and head and neck cancers. (See 'Epidemiology' above.)
●Biopsychosocial model – Using the biopsychosocial model (figure 1), clinicians can comfortably and thoroughly assess female cancer survivors for sexual dysfunction; offer specific therapeutic interventions, medical management, and education; and refer them for sexual counseling and/or rehabilitation if treatment is beyond their expertise. (See 'Overview of the biopsychosocial model' above.)
●Causes of sexual dysfunction – Common causes that impact sexual health include both primary therapies (eg, surgery, chemotherapy, radiation therapy, endocrine therapy), secondary etiologies related to cancer treatment, and psychological distress. (See 'Causes of sexual dysfunction' above.)
●Screening and counseling – When screening for sexual dysfunction, we prefer ubiquity-style inquiry and brief screening tools over patient-reported outcome questionnaires, which may be too time- and labor-intensive to incorporate into routine clinical practice. Although barriers exist, female cancer patients can be screened and counseled on sexual dysfunction in both the pretreatment and posttreatment settings. (See 'Screening and counseling' above.)
●Diagnostic evaluation – The diagnostic evaluation of a female cancer patient with sexual dysfunction includes a complete medical, gynecologic, and sexual history as well as a physical examination directed at treated organ systems (eg, breast, pelvic examination) and/or specific symptoms. Further diagnostic testing may be indicated, including evaluation for sexually transmitted diseases, vulvar and pelvic imaging, or diagnostic nerve blocks. (See 'Diagnostic evaluation' above.)
●Management – The management of sexual dysfunction in female cancer survivors includes both education and treatment directed at specific symptoms such as dyspareunia, vaginal stenosis, decreased libido and arousal, and anorgasmia. Patients should be provided access to a multidisciplinary treatment team with expertise in the management of sexual dysfunction in cancer survivors. (See 'Management' above and 'Treatment team and referral' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Sandy J Falk, MD, FACOG, who contributed to earlier versions of this topic review.
