Alessandra Graziottin1, 2 , Monika Lukasiewicz3 and Audrey Serafini4
(1)
Center of Gynaecology and Medical Sexology H. San Raffaele Resnati, Via Enrico Panzacchi 6, Milan, Italy
(2)
Foundation for the Cure and Care of Pain in Women – NPO, Milan, Italy
(3)
IInd Department of Obstetrics and Gynaecology, University of Warsaw, Medical Center for Postgraduate Education, Belanski Hospital, Warsaw, Poland
(4)
San Raffaele Hospital, Milan, Italy
Alessandra Graziottin
Email: a.graziottin@studiograziottin.it
Email: segreteria1@studiograziottin.it
URL: http://www.alessandragraziottin.it
URL: http://www.fondazionegraziottin.org
Keywords
Sexual rehabilitationGynecologic cancersCervical cancerUterine cancersOvarian cancersVulvar cancersRadiotherapyChemotherapyPelvic floorDyspareuniaNeuroinflammation
27.1 Introduction
Women’s quality of sexual life is an urgent issue in gynaecological oncology. The multifactorial etiology of gynaecological cancers (GC) and the increasing prevalence of such cancers at younger ages require a comprehensive medical and psychosexual perspective, even more so when sexual rehabilitation is the ultimate goal. The high rate of long-term survival makes GC more of a chronic than a fatal disease. Premature iatrogenic menopause is an important factor to be considered.
GC may impact women’s sexual identity, sexual function, and sexual relationships in a number of significant ways [1] (Table 27.1). Unfortunately, sexual issues are still almost entirely neglected during clinical consultations.
Table 27.1
Prevalence of female sexual dysfunction after gynaecological cancer [1, 2, 5]
|
The cancer and its treatment can cause short-term and long-term effects on sexuality, reproductive function, and overall quality of life [1, 2, 5]. In women treated for GC, available evidence indicates that: |
|
Loss of sexual desire is reported from 38.4 to 68.3 % of women |
|
Arousal problems, with vaginal dryness and coital difficulties are complained by up to 80 % of women |
|
Orgasmic difficulties are reported by up to 75 % of patients |
|
Dyspareunia in survivors ranges from 21.9 to 62 %. Comorbidity between dyspareunia and bladder symptoms can be as high as 60 % |
The life-threatening nature of cancer tends to let sexuality in the shadow of more urgent treatments, also because sexuality is not considered to play a crucial role in the life of survivors. In spite of this belief, women survivors of GC today look for a fulfilling sexual life. In an American study [2], 74 % of patients believed their physicians should discuss sex, yet such discussions did not occur in the vast majority of cases. Indeed, 62 % of the cases and up to 90 % of women after GC may experience a loss in quality of life (QoL) and sexual difficulties [1, 2] (Box 27.1).
Box 27.1 Sexuality After Cancer Experiences in Patients’ and Partner’s Wording*
Luciana, 48 years old, iatrogenic menopause at 45 years of age for cervical cancer.
“I started suffering from insomnia, hot flushes, arthralgia. I had difficulties during intercourse. I thought it was going to pass over, but it got worse, and now I have small vulvar cuts which burn every time I try to have an intercourse! I feel so old and I am only 48!”
Carmen, 58 years old, iatrogenic menopause at 51 years of age for endometrial cancer
“I am so dry down there. It hurts so much that every time I have sex I feel like being raped! I told to my husband to look for another woman, because I can’t stand this pain anymore!”
Silvana, 49 years of age, iatrogenic menopause due to radiotherapy for cervical cancer.
“Radiotherapy is insidious. Its dramatic effect arises slowly. Nobody told me before that my vagina would have been closed. Nobody explained me before how to avoid it. I know that the main goal of therapy is to treat cancer, but I believe it is important to be taught how to reduce radiotherapy’s damage. Now I can’t insert anything in my vagina and I bleed if my husband tries to touch me. This is not life anymore…”
Marco, 48 years old, employed. Partner with adenocarcinoma of the cervix
“Four years ago, when she was 37, my wife had cancer. She was very brave, and faced everything with courage. She went through surgery, chemotherapy and radiotherapy. Now she is suffering from severe articular pain. She gained 20 kg. She is not herself anymore. It’s two years now that we don’t have intercourse, because she was bleeding and suffering too much pain at every attempt. So I stopped asking her. I will never break up with her, because I am very affectionate to her and we have two kids. But I feel a caregiver, not as a husband anymore. And now I have a mistress, because I need to feel alive again.”
Marcello, 65 years old, butcher. Partner had endometrial cancer.
“I understand that she had cancer, but I still need sex. I can’t stand lubricants! They are cold… I feel like entering in a refrigerator, not making love! I’ve been patient for two years, but I do not want to give up sex forever! I told my wife: find a decent solution, or I will ask for divorce!”
*The wording is spontaneously reported during the clinical consultation or the gynaecological examination.
To fully understand the complex, multifactorial etiology of biological and psychosexual disruptors of sexuality during and after GC treatment is demanding and of prime ethical and human value. It is a prerequisite to address them in a multifactorial comprehensive approach.
Ideally, the first assessment should be at the moment of the cancer diagnosis, to report/evaluate any sexual complaint already present in the woman and, when there is a stable relationship, in the couple [3]. The goal would be to prevent further complications secondary to cancer treatment.
27.2 Epidemiology
In developed countries, the most common types of gynaecological cancer are endometrial cancer (22.7/100.000 women/year) and ovarian cancer (15.7/100.000). These generally occur in postmenopausal women, while cervical cancer (in the vast majority of cases induced by human papillomavirus) is present earlier in life with an incidence of 12.1/100.000 women per year. Whereas the vulvar cancer incidence is 2.5/100.000 and vaginal cancer is very rare, their impact on quality of life and sexuality can be devastating.
27.3 Etiology of FSD
The etiology of FSD in women with gynaecological cancer is multifactorial. Sexual “comorbidity,” that is, the coexistence of impairment in sexual desire/interest, arousal, and orgasm with increased dyspareunia, is significantly increased in these cancer survivors (see Table 27.1).
The most relevant etiological factors are as follows:
27.3.1 Biological
27.3.1.1 Cancer Dependent
Based on: cancer histotype and stage and by recurrences, if any. The longer the time from the primary cancer treatment, the higher the probability of survival in gynaecological cancer.. Sexual life can be enjoyed again, if sexual counseling and rehabilitation are timely provided, particularly before and during vaginal/pelvic radiotherapy, which may present the most serious sexual damage.
27.3.1.2 Treatment Dependent
· Surgery: Conservative versus radical, chemotherapy, and/or radiotherapy (RT), with successful nerve sparing or not.
· Type of surgery: In general, the more radical the surgery, the higher the probability of sexual dysfunctions and bladder symptoms. The most frequent complaints include vaginal shortening, vaginal dryness (unless hormonal therapy is prescribed), introital and deep dyspareunia, coital orgasmic difficulties, and significant bladder comorbidities.
Lymphedema of the lower limbs and, in a few cases, of the vulva, may further significantly affect body image and body feelings, cause depression, and contribute to further reduced sexual drive/interest and motivation for sexual intimacy.
· Nerve sparing: These approaches may contribute to a better sexual function and to a more competent bladder, with reduced bladder comorbidities [4].
· Surgery and RT: QoL is less disrupted by surgery alone than by surgery with additional treatment modalities (CT and/or RT).
Radiotherapy appears to be the most insidious treatment, because it causes scarring of the irradiated tissues and progressive shortening and stenosis of the vagina, which may completely prevent penetration, unless appropriate sexual rehabilitation is provided early on. Topical and/or systemic estrogens, when indicated, may further contribute to maintaining lubrication and elasticity. Topical testosterone may further contribute to maintain a better cavernosal and vaginal vascular response (III) [1, 5]. However, no controlled data are available on testosterone treatment in cancer patients.
· Radiation therapy: Women treated with radiation therapy alone are at higher risk of impaired sexual function in comparison to women not receiving radiation. In addition to the symptoms already listed earlier, RT may cause spontaneous or contact bleeding, which can be a very frightening symptom as it may remind the woman, and her partner, of the original reason that led to the cancer diagnosis.
· Chemotherapy: Usually combined with surgery, leads to fatigue, hair loss and skin changes, inducing “feeling like a monster,” loss of sex appeal, seductiveness and beauty, weight changes, nausea, and diarrhea, deeply affecting body image, body feelings, and confidence of one’s sexual attractiveness. Overall, chemotherapy usually has the strongest impact on women’s sexual identity.
Moreover, treatment-related sexual and nonsexual comorbidities may further contribute to impair the biological basis of women’s sexual function after GC diagnosis and treatment:
· Iatrogenic menopause: It causes intense and sudden menopausal symptoms (hot flashes, sweating, insomnia, tachycardia, joint pain, sexual dysfunctions – loss of libido, vaginal dryness, introital dyspareunia), concentration and memory difficulties, reduced assertiveness, low vital energy, loss of pubic hair, and reduced muscle mass, with a major impact on body image, body feelings, sexual drive, and motivation.
· Infertility: It is a major depressing factor in childless women. Women who considered the uterus and the ability to bear children as a main part of their femininity reported lower self-esteem and more negative body image after GC treatment [6]. Procedures for fertility preservation reduce the health and sexual impact of GC treatment.
· Urinary incontinence: It is a direct consequence of the disruption of the sensory and motor nerve supply of the detrusor, with deterioration in detrusorial and urethral sphincter competence.
· Genital anatomical and cosmetic impairment: Vulvectomy is the most disrupting surgical intervention, with short- and long-term genital and sexual consequences.
· Negative feedbacks from the genitals: Secondary to anatomical changes and vulvar/genital paresthesias and/or pain, cosmetic impairment, vulvar lymphedema, vaginal dryness, anatomical vaginal changes, dyspareunia, lack of orgasm, and bladder symptoms may further worsen sexuality acting both on body image/body feelings and causing depression, loss of sex drive, and motivation. Genital lymphedema is particularly devastating and difficult to be medically treated.
· Neuroinflammation: A growing body of evidence indicates that neuroinflammation is a major issue in oncological patients [7]. Inflammatory cytokines, tumor necrosis factor-alpha, and many other inflammatory markers increase significantly in cancer patients, with peaks following surgery, chemotherapy, and radiotherapy. The increase of inflammatory markers reaching the brain and the parallel hyperactivation of the microglia contribute to neuroinflammation, the powerful biological basis of depression, sleep disorders, fatigue and sickness behavior, and loss of vital energy and of sexual drive typical of the cancer treatment phase [7].
27.3.2 Psychosexual
Psychological distress was noticed in 45 % of cancer survivors. Psychosexual etiology may be:
· Woman-dependent, depending on age at diagnosis (the worse outcome on sexual identity is more likely in younger patients who have not yet fulfilled their major life goals, like falling in love, achieving the desired career, getting married, or having children), and also by premorbid personality and sexual well-being and by preexistent psychological–psychiatric problems.
· Cancer and treatment dependent: Psychological distress may be exacerbated by distress combined with chronic fatigue, which is the symptom most complained of by cancer patients and the least listened to by physicians. And also by the impact of surgery, CT or RT on the woman’s sexual identity, body image, and body feelings.
· Socioeconomic and context dependent: GC survivors are 1.4 times more likely to be unemployed than healthy women and less likely to return to their job than other cancer survivors. Neurocognitive functions are significantly affected in patients treated with CT, because of the associated neuroinflammation.
Moreover, quality of support in the couple and family and from health care providers is critical for the psychological outcome after treatment (Box 27.2).
Box 27.2 The Impact on Sexual Function According to Type of Cancer
Specific factors related to the type of cancers may differently impact on the sexuality of the woman and the couple.
· Cervical cancer. It is most common in women around 40 years of age, due to the early onset of sexual intercourse and to a higher promiscuity at early ages. The emerging trend is to treat it with minimal surgical removal of tissue, as it is in radical trachelectomy (which is feasible in 48 % of cases), to minimize long-term negative sexual and reproductive consequences (Table 27.2). Women with invasive cancer that are treated either by RT or radical surgery suffer significantly more often from sexual impairment.
Table 27.2
Main biological side effects after treatment for cervical cancers
|
After surgery |
|
Radical hysterectomy; sexual side effects |
|
Lack of desire/interest/motivation |
|
Decreased vaginal lubrication/dryness |
|
Shortening of vagina |
|
Introital and deep dyspareunia |
|
Lack of sensations in the labia |
|
Infertility |
|
Urinary complications |
|
Voiding disorders |
|
Urinary infections |
|
Vesicular fistulae |
|
Intestinal problems – ileus, fistulas, obstruction, wound infection |
|
Pelvic abscesses |
|
Ovariectomy |
|
Iatrogenic premature ovarian failure (POF) or insufficiency (POI) |
|
Lymphadenectomy |
|
Leg and/or genital lymphedema, monolateral or bilateral, according to the level and extension of the lymphadenectomy |
|
After radiotherapy |
|
Vaginal and pelvic fibrosis (“frozen pelvis”) |
|
Sexual dysfunction (vaginal dryness, narrowing/shortening of the vagina, bleeding/spotting, introital, and deep dyspareunia) |
|
Bladder and rectal complications: incontinence, cystitis, diarrhea, and pain |
|
After chemotherapy |
|
Cosmetic issues |
|
Iatrogenic premature menopause |
|
Long-term peripheral neuropathies |
|
Neuroinflammation and depression |
Modified from Lukasiewicz and Graziottin [5]
· Endometrial cancer. 1.6 % are diagnosed between the ages of 20 and 34, and 6.1 % between 35 and 44 years. However, this cancer is mostly diagnosed in the postmenopausal age. In its early stages, it has a 5-year survival rate as high as 96 %. The standard treatment is total hysterectomy and bilateral ovariectomy, with or without pelvic and para-aortic lymph-node dissection. Survivors report significantly more sexual dysfunctions compared to controls.
· Ovarian cancer. 90 % of all OC are epithelial ovarian cancers, with an incidence rate, in women up to 40 years of age, reported to be between 3 and 17 %. The main treatment for ovarian cancer is surgery with optimal debulking, that is, maximal reduction of the visible cancer mass. Almost all patients receive adjuvant therapy. In terms of femininity, the most devastating is chemotherapy.
· Vulvar cancer It is treated by broad local excision, hemi- or total vulvectomy. In addition, unilateral or bilateral inguinal lymphadenectomy is performed. Sentinel lymph node procedure is used to reduce morbidity and improve QoL. After lymphadenectomy, patients are at high risk of lymphedema of the vulvar/genital region, extending to the lower limbs (either monolaterally or bilaterally). This is a chronic progressive condition associated with decreased QoL due to poor self-esteem/body image, poor appearance/leg “deformity” and constant “heaviness,” mobility limitations, and self-image concerns. Lymphedema seems to be the only factor influencing the patients’ sexual function: patients without lymphadenectomy or with sentinel node biopsy scored better in terms of sexual function than patients who underwent lymphadenectomy.
· Vaginal cancer: No specific studies have addressed the sexual impact of this rare tumor.
27.4 Psychosexual and Relational Outcomes After GC: The Challenge of Rebuilding Couple Intimacy
When the well-being of family members is threatened, the distress may worsen the burden of biological factors, further affecting a couple’s sexuality after GC. The main psychological, sexual, and relational outcomes are summarized here. The impact is higher in younger couples without children or with children at primary school age (Table 27.3).
Table 27.3
Variables that influence the impact of genital cancer on the couple’s relationship
|
Type, stage of the cancer, and treatment required |
|
The status of the relationship before the cancer developed |
|
The level of fulfilment of family projects (having children, etc.) |
|
The duration of the marriage/relationship |
|
The interpersonal skills of the partner |
|
Personality, attitudes, and coping strategies of the partner (either a he or a she) |
|
Quality of contextual professional and emotional support |
|
The point in the course of the illness when the evaluation is made |
Modified from Lukasiewicz and Graziottin [5]
· Psychological outcome: Sick women may experience fear of death, which may marginalize the need of a sexual life for a period of time, worsening the couple’s intimacy and relationship. Moreover, women often feel ashamed and embarrassed for their condition and may feel rejected by their partners, for fear of being unattractive. Treatments cause a change in body image and body feelings. Women often experience a feeling of loss of control of their own body, which may change their sexual self-schema and sexual identity, impacting on the couple’s well-being. The knowledge of the nature of their condition and the changes in their quality of life may lead the affected women to experience a worsening anxiety and depression.
Depression has two major contributors: (a) the knowledge of having a life-threatening condition; (b) inflammatory cytokines, tumor necrosis factor alpha, and many other inflammatory markers increase significantly in cancer patients, with peaks following surgery, chemotherapy, and radiotherapy. The increase of inflammatory markers reaching the brain and the parallel hyperactivation of the microglia contribute to neuroinflammation, the powerful biological basis of depression, sleep disorders, fatigue and sickness behavior, loss of vital energy, and of sexual drive typical of the cancer treatment phase [7]. Inflammation is clearly the common denominator to both pain and depression, initiating the activation of several pathways that can trigger the transition from sickness to depression and from acute to chronic pain, particularly stemming from peripheral neuropathies. Understanding neuroimmune mechanisms that underlie depression and pain comorbidity may yield effective pharmaceutical targets that can treat both conditions simultaneously beyond traditional antidepressants and analgesics.
· Sexual outcome: Women with a life-threatening condition usually deal with a loss of desire and motivation for sexual activities. Moreover, physical conditions such as vaginal dryness, introital, and deep dyspareunia worsen this condition, causing pain, orgasmic difficulties, and physical and emotional dissatisfaction.
· Relational: Having a genital cancer may have a negative impact also on the partner and on the family. Couple problems are indeed very common in these cases, especially in younger couples, for the higher relevance that the sexual relation has in everyday life, and also for the fear of being contagious to the partner, in HPV-related cancers, and the guilty feelings in regard to past personal and partner’s sexual behaviors. Also, the opposite is common: women may experience aggressive feelings against the partner considered responsible for the infection (of having “caught” it) and the subsequent cancer.
27.5 Sexual Relationship Considerations
What about the partner? As clinicians who care, we should be aware that the male partner may experience sexual dysfunction induced by the partner’s cancer condition (Table 27.4). Examples of partner’s wording are reported in Box 27.1.
Table 27.4
Key issues of male sexual partner of GC survivors
|
Sexual |
|
Loss of men’s sexual desire due to: |
|
1. Impact of the iatrogenic menopause on the woman’s sexual appeal |
|
2. Changes in the aesthetic/cosmetic/visual appearance of the female genitals |
|
3. Type, extension, and duration of treatment |
|
4. Recurrences have a specific negative burden on the psychosexual adjustment and potential for hope in both partners |
|
Difficulty in penetration because of vaginal dryness, stenosis, retraction, and the feeling of vaginal shortness |
|
Loss of pleasure in oral sex because of: |
|
Loss of the “scent of woman” due to changes in genital scent caused by premature menopause, loss of estrogens, and related changes in the vaginal ecosystem and perfume of vaginal secretions |
|
Changes in the taste of vulvar skin and vaginal secretions due to loss of sexual hormones, but also because of the aversive taste of vaginal creams and suppositories |
|
Her loss of interest in sex due to fatigue, iron deficiency anemia, loss of energy, depression, and pain |
|
Her orgasmic difficulties because of loss of testosterone (after ovariectomy or CT or RT) and consequences of treatment |
|
Fear about his ability to obtain or sustain an erection: |
|
1. Vaginal dryness itself can challenge the quality of the erection, and it can be perceived as a sign of refusal and/or an indication of the “unsensitivity” of his sexual request and approach. |
|
Psychosocial |
|
Difficulties in communication for: |
|
The taboo of discussing intimate sexual issues |
|
The fear of hurting the cancer survivor |
|
Reactive anxiety, depression, and uncertainty about the future |
|
Fears and concerns related to additional roles and family responsibilities during diagnosis, treatment, and recovery |
|
Feelings of guilt about wanting to increase sexual intimacy or having a new partner |
Modified from Lukasiewicz and Graziottin [5]
Key issues of the sexual partners of GC survivors are as follows:
· Sexual: Men may experience loss of sexual desire due to the impact of the iatrogenic menopause on the woman’s sexual appeal and the changes in the aesthetic/cosmetic appearance of the female genitals. Moreover, penetration may become very difficult because of vaginal dryness, stenosis, and the feeling of vaginal shortness. Premature menopause, loss of estrogens, and related changes in the vaginal ecosystem may change the perfume of vaginal secretions causing a loss of pleasure in oral sex because of the loss of the “scent of woman” and of the lovely arousing taste of natural vaginal secretions.
The woman’s loss of interest in sex due to fatigue, loss of energy, depression, and orgasmic difficulties because of the consequences of treatment may impact on male arousal and cause difficulty in obtaining or sustaining an erection, especially when vaginal dryness is present as it is perceived as a sign of refusal and/or an indication of the “insensitivity” of his sexual request and approach.
· Psychosocial: Not only physical intimacy but also psychological intimacy is in danger during important health issues as in the case of cancer. It is very difficult for the partner to communicate his concerns to the physician, in the presence of the partner, due to fear of hurting the cancer survivor. The possibility and usefulness of individual consultations for the partner should always be considered and offered. The inability in communicating may lead to reactive anxiety and depression. Moreover, uncertainty about the future leads to fears and concerns related to additional roles and family responsibilities during diagnosis, treatment, and recovery. Finally, it is not uncommon for the partner to experience feelings of guilt about wanting to increase sexual intimacy or having a new partner and to have difficulties in coping with the illness of the partner and the “burden” of the family [1].
The main worries of partners of GC survivors are usually more intense in the case of limited/absent communication: 50 % of younger patients felt that more information about sexual changes should have been given to their husbands as well. On the positive side, factors predicting healthy sexual adjustment are illustrated in Table 27.5 [6, 8].
Table 27.5
Factors predicting healthy sexual adjustment after treatment
|
Good emotional and affective relationship |
|
Open couple communication |
|
Satisfying sexual relationship before the diagnosis |
|
Support from sexual partner |
|
Partner’s sexual health and desire for sex |
|
Quality support from health care providers |
Modified from Lukasiewicz and Graziottin [5]
These six parameters should be kept in mind as an inner referral when psychosexologists are working with the couple, with the goal of implementing them at their best
27.6 Sexual Rehabilitation After Gynaecological Cancer Treatment
We start with a more general remark about the potential damage of a minimalistic approach.
27.6.1 Avoiding the “Collusion of Silence”
This is an important first step in treatment. Women often feel ashamed and embarrassed to speak about sexual issues with their health care provider. The majority of women think that vaginal atrophy and vulvar pain is normal and an unavoidable event during and after treatment for gynaecological cancer. One-third of women would not even speak about this concern with the partner. Although it is the physician’s responsibility to raise the problem, it is rarely done: half of the physicians do not raise the subject and only 14 % of women who did discuss symptoms received a diagnosis and an effective treatment for their sexual disturbances.
Before surgery, sexuality issues should be explained to the patients. This intervention can turn into a main predictor of post-diagnosis marital adjustment [2, 3, 6].
27.6.2 Avoiding Minimalistic Treatment
What happens when a sexual problem is raised? After gynaecological cancer, the majority of women who ask after-solutions for their sexual concerns receive a lubricant as an answer. This is perceived as humiliating by the woman and as a deception by the man. On the one hand, a lubricant is not enough to rehabilitate the female genital tract, as it is like lubricating a rigid tube. On the other hand, it is perceived as a humiliating fiction of arousal by the couple (see partner’s wording, Box 27.1).
27.7 Treatment Strategies
27.7.1 Preventive Approaches to Be Recommended During Surgery (When Oncologically Appropriate)
· Sentinel node biopsy to avoid leg lymphedema
· Nerve-sparing techniques to preserve bladder function and sexual function
· Ovary conservation to prevent premature menopause and to maintain a better sexual function and body image
27.7.2 Preventive and Rehabilitation Approaches
We distinguish five different areas:
1. (a)
2. (b)
3. (c)
4. (d)
5. (e)
27.7.2.1 Hormonal Pharmacological Treatments
· Topical estrogens (estradiol, estriol, promestriene, conjugated estrogens) should be prescribed soon after surgery. This is even more important in case of shortened vagina after cervix cancer, in case of cervical squamous carcinoma, or with vulvovaginal atrophy. Estriol has 1/80 of estradiol potency, and it is the safest estrogen (as it has a prominent action on estrogens receptors beta, which have antiproliferative and reparative actions). It can be used in the form of vaginal gel or vaginal suppositories, every other day, to maintain a healthy vaginal and bladder condition. Estrogens have an effect on vaginal epithelium, diminishing postmenopausal vulvovaginal atrophy. They keep the vaginal pH in the healthy range, thus decreasing the incidence of E. coli vaginitis and lower urinary tract infections [9]. They also have a protective effect on urethra and bladder, thus reducing urinary incontinence, overactive bladder, and recurrent postcoital cystitis (Box 27.3).
Box 27.3 Key Points in Local Estrogen: Proper Timing and Lifelong Treatment
· The “window of opportunity” concept, well accepted for postmenopausal hormone use to prevent/reduce cardiovascular and brain problems, is even more true for the vaginal dryness and atrophy after oncological gynaecological treatment: “the sooner the better” is the motto. The delay in the hormonal treatment, at least vaginal, leads to nonreversible atrophic change, tissue retraction, and scarring, particularly after radiotherapy, which forever could affect the woman’s sexual life.
· Lifelong treatment. For her vagina, the woman needs estrogen, at least topical, until the end of her life, and not only for a short period of time (for the very same reason why we do not use insulin “for the shortest period of time”). At least topical hormonal treatments (such as estriol in gel) should be considered lifelong, if the goal is to prevent and cure the vaginal/bladder consequences of menopausal estrogen loss and of oncological treatments that further threaten the woman’s and couple’s sexual health in the long term. The exceptions are hormone-dependent cancers like adenocarcinoma of the cervix or cancer of the breast.
Systemic estrogens: After hysterectomy, women can use estrogens without addition of progesterone (the progestins are only needed to protect the endometrium). The good news for women and clinicians is that the Women’s Health Initiative study clearly indicated that the postmenopausal treatment with only estrogens in hysterectomized women significantly reduces the risk of breast cancer (<23 %), while it maintains all the benefits on cardiovascular system, brain, bones, joints, gastrointestinal, urogenital system, and on sensory organs, skin, and mucous membranes [10]. It can therefore be used in the long term, if symptoms persist. However, as the systemic administration may not be sufficient to guarantee a normal vaginal lubrication [11], topical estrogens should be added to optimize the functional outcome. Hormones may be used after squamous cell carcinoma of the cervix or if bilateral ovariectomy has been performed (for cancers different from adenocarcinomas).
· Testosterone: Topical, as cream of testosterone propionate (2 %) or testosterone of vegetal origin. Testosterone is indicated not only after ovariectomy [12], but also after pelvic radiotherapy or chemotherapy, as both can destroy the testosterone-producing ovarian Leydig cells. In all these cases, women lose more than 50 % of the total testosterone with sexual symptoms (loss of desire/interest and drive, of systemic and genital arousal, reduced lubrication, and cavernosal congestion and impaired orgasm) and systemic symptoms (depression, low vital energy, fatigue) unless testosterone is replaced. In addition, an early menopause is accompanied by an anticipated adrenopause for the part of the adrenal that synthesizes DHEA. After 3 months of topical treatment, women report a more rapid genital congestion, more intense feelings of pleasure, and a reassuring orgasm “comeback.” Partners report that the physical response of the woman is more gratifying for both partners. Anecdotically, partners report that with topical testosterone treatment, even the scent and taste of vaginal secretions and vulvar skin are much more pleasurable.
· DHEA
DHEA has several benefits. Applied topical in the form of cream, it apparently enhances vaginal lubrication.
When used systemically (orally 10 or 25 mg daily), the majority of women report more energy, more positive feelings, increased muscle tone, and strength. This strongly contrasts with the sarcopenia, typical of aging, menopause, and the hospitalization during cancer treatment. In addition, DHEA gave an overall positive impact on mood and sexuality. A skilled clinician could tailor the hormonal treatment according to the woman’s expectations with excellent results in terms of improved general and sexual well-being [13].
27.7.2.2 Nonhormonal Medication
Various nonhormonal medication (antidepressants, hypnotics, etc.) can be considered in hormone-dependent cancers to ease menopausal and sexual symptoms.
Tips and tricks for a better sexual survival after gynaecological cancer
· Treat iron deficiency anemia: The relationship of iron to brain function, cognition, and behavior, including affective behavior, has been a subject of interest during the past decades. Iron deficiency anemia is associated with disturbances in behavior related to responsiveness, unhappiness, and alertness. More recently, disturbances in iron metabolism have been suggested as potential pathological markers in depressed patients. Iron deficiency anemia is correlated to chronic fatigue, which may exacerbate depressive symptoms and inertia. So, in the (sexual) rehabilitation after cancer, it is important to consider iron deficiency as one of the potential disturbing factors, indicating appropriate diagnosis and eventually restore adequate iron levels.
· Treat vitamin D deficiency. In addition to its role in calcium and bone homeostasis, vitamin D potentially regulates many other cellular functions. Observational studies suggest an association between poor vitamin D status, muscle weakness, and regulation of the immune system. So, vitamin D supplementation should be considered if the woman is found deficient after cancer treatment.
· Antidepressants. Depression not only causes great mental anguish, but it also interferes with the fundamental biological processes that regulate inflammation, coagulation, metabolism, autonomic function, neuroendocrine regulation, sleep, and appetite. Antidepressants have a double mechanism of action: the inhibition of the serotonin reuptake and the recognized anti-inflammatory potential, which may both contribute to treat depression due to cancer and to the general inflammatory state correlated to it [14].
· Alpha-lipoic acid (ALA) (300 mg capsule twice daily) is a potent natural antioxidant, which has been associated with the benefit for symptomatic diabetic neuropathy. ALA and its reduced form – dihydrolipoic acid (DHLA) – are ideal antioxidants, because they easily quench radicals, chelate metals, and do not exhibit any serious side effects. The therapeutic action of ALA, based on its antioxidant properties, can be used to reduce pain in multiple organs and tissues. It is of special interest in case of peripheral neuropathies after chemotherapy and/or radiotherapy. Clinical studies support this with 300 mg twice daily reporting improvement of peripheral paresthesia after chemotherapy.
· Palmitoylethanolamide has a powerful anti-inflammatory, antalgic, and antidepressant effect as it contributes to reducing the neuroinflammation associated with cancer treatment. It has a systemic and peripheral action (600 mg twice a day in capsules or sublingual).
· Hyaluronic acid for improved lubrication and the condition of the vagina. To be given topical, as vaginal gel or suppositories, once a day until symptom relief has been obtained, and then one application every other day, in the evening. It is almost comparable to the local efficacy of estriol [1, 5].
· Colostrum vaginal gel has powerful reparative action on the vagina’s mucosa and is particularly useful in case of vaginal dryness.
· Moisturizers hydrate the vaginal mucosa and usually keep the vagina moisty for several days. It is a nonhormonal way for overall vaginal health and comfort, regardless of sexual activity (although it can offer sexual benefits as well).
· Lubricants are intended for the sexual context. Many women and partners do not like the “fiction of arousal” of artificial lubricants. However, they are sometimes needed if the couple desires vaginal penetration. Normally, good arousal causes proper lubrication. However, when the physiology of lubrication is damaged (for instance, by radiotherapy or beta-blockers), an artificial lubricant is a necessity. Good sex shops tend to have brands with a good feel, taste, and smell.
Lubricants should also be used when training with vaginal dilators.
27.7.2.3 Nonpharmacological Approaches
· Physiotherapeutic rehabilitation: Physiotherapists, and also specifically trained nurses and midwives, can have an important role in various aspects of pelvic floor rehabilitation.
This aspect of rehabilitation includes the use of vaginal dilators, especially after pelvic radiotherapy, to reduce the impact on vaginal elasticity and receptiveness. The information on such vaginal/sexual rehabilitation should be provided by the radiation oncologist before treatment, at least in all the women younger than 70 years. Specifically trained oncology nurses, who naturally have to be more prone to deal with the intimacy of their patients, seem the best to provide medical, practical, and psychological support when vaginal dilators are indicated.
Recommendations for dilation are for instance to start 4 weeks after treatment, to be done two to three times per week for 1–3 min and to be continued for 9–12 months. In our own practice with earlier start and twice daily use of 5 min, we see good outcomes in terms of vaginal sexual elasticity, receptiveness, and “habitability.”
Moisturizers and lubricants usually are needed to ease dilation. When there are no contraindications, the care should include preliminary hormonal treatment, since dilators and topical estrogen therapy can synergize in reducing vaginal dryness and dyspareunia and regain vaginal health.
· “Hands-on” pelvic floor rehabilitation may further contribute maintaining elasticity through appropriate stretching, massage, and physiotherapy.
· Regular sexual activity. If not undesired, this has great benefit in preventing vaginal atrophy. When gently guided, the penis can act as a dilator. The additional genital arousal and its neurovascular response is likely to promote genital regeneration and health. Although this is a delicate area, proper guidance can lead to great benefit for the patient and couple.
· Mechanical arousal. The additional benefit of genital arousal can also be evoked by using a mechanical device, for instance, by a vibrating dilator. Vibration carried on to orgasm can serve as a motivator for the homework.
Eros® is a small clitoral suction device, recommended after vaginal radiotherapy, with benefits both for sexual and for vaginal health [15].
· Lymphedema treatment. When lymph node removal is expected to cause (or has caused) lymphedema. Within the expertise of the lymphedema (physio)therapist, there are various elements like lymph drainage with specific massage techniques; compressive stocking; specific physical exercises; and sometimes medication (Diosmin–Hesperidin).
27.7.2.4 Psychological/Psychosexual Approach [1, 5, 6, 8]
Sexual self-schema, or sexual self-concept, creates a cognitive view of sexual aspects of oneself derived from past experiences and often expressed in current experience. Sexual self-schema may account for variance in predicting current sexual behavior after cancer. The survivors with a positive sexual self-concept may adapt more positively. Recently, studies have noted the success of brief psychosexual interventions and of addressing the informational and sexual needs of cancer patients. Mindfulness training incorporated in a psychoeducational program for women with arousal disorder subsequent to gynaecological cancer has been effective in preliminary studies [16]. An effective method of treatment for sexual difficulties in cancer patients is through the coordinated provision of information, support, and symptom management, preferably at one site. Many cancer institutions have established comprehensive multidisciplinary programs. The focus is on both the psychosexual and physical aspects of sexuality. Some research shows a connection between increased compliance with therapy and subjective improvement in sexual symptoms. Palliative care providers can also be involved as they reassure patients and their partners that even at the end of life, when intercourse may not be feasible, physical sexual intimacy and emotional closeness can be encouraged and are worthwhile in a committed relationship.
27.7.2.5 Lifestyle Adaptations
The Challenge of Improving Lifestyles After Cancer
· Optimal weight. Weight reduction may improve cancer outcomes. It also can improve body image, self-perception, vital energy, and sex drive, especially when combined with daily physical activity. It also reduces the general inflammation, decreasing the risk of depression and pain.
· Physical exercise: It is important to avoid sarcopenia, which is more prevalent with increasing age, with iatrogenic menopause, and with long-lasting cancer-related hospitalization. An increasing number of studies have underlined the role of regular physical activity during and after treatment in improving cancer prognosis and overall survival, although the precise mechanisms are not fully understood. The most often cited improvements are reduced systemic and neuroinflammation, reduced depression and better immune functioning, better sleep (the great guardian of health and sexuality), and reduced fatigue and distress. Physical activity helps also to mentally and psychologically redesign the patient’s body map, giving the correct importance to all of the body parts and not focusing only on the sick part. Exercise also has an impact on the dopaminergic system, increasing dopamine secretion. It is likely that all these factors positively influence sexuality as well, although no specific research has yet been conducted.
· The importance of the diet: The American Cancer Society (ACS) and the American College of Sports Medicine (ACSM) have developed nutrition and physical activity guidelines for cancer survivors, linking diet, weight, and physical activity to cancer outcomes.
Key points of the ACS/ACSM recommendations include:
· Maintain a healthy weight and attempt weight loss if overweight or obese
· Adopt a physically active lifestyle, engaging in at least 30 min of moderate to vigorous physical activity on 5 or more days of the week
· Consume a healthy diet, with at least five servings of fruits/vegetables per day and limited ingestion of processed foods and red meats
· Limit alcohol to no more than one drink/day and avoid smoking. Alcohol and smoking may exacerbate inflammatory conditions and have a detrimental mental effect.
· The importance of sleeping: Protect the sleeping quality, also with the help of melatonin, a natural circadian sleep hormone (which, by the way, has an anti-inflammatory effect).
Conclusions
Gynaecological cancer may affect women’s sexual identity, sexual function, and a couple’s relationship both biologically and psychosocially. The role of biological factors, with the exception of RT damage, has only been marginally addressed, while psychosocial factors have been studied in retrospective and prospective studies. The goal of maintaining and restoring the best possible sexual life (penetration included!), and as such increasing the sexual health span, should be present in the physicians’ and psychosexologist’s mind in every step of cancer treatment. The more this principle is respected, the better the outcome.
This chapter is extensively based on the author’s clinical experience of decades of sexual rehabilitation after gynaecological cancer. The evidence supporting the pharmacological choices is huge, but usually not specifically evaluated in cancer patients. The pioneering use of many treatments in this specific field deserves clinical trials to specifically evaluate its impact and significance. For example, it may be worth evaluating the best intervention for vaginal dilator use, to determine which of the minimally absorbed local vaginal estrogen products (ring, tablet, or cream) best restores vaginal integrity and sexual satisfaction, and the safety of intravaginal DHEA and testosterone for this particular group. The specific role of SERMs such as ospemifene, and of nonpharmacological treatments such as ALA, PEA, or hyaluronic acid, should be evaluated. Prospective clinical trials including patient-reported outcomes are also needed to identify subgroups at risk. Future studies should then address the impact on sexual outcome of less aggressive and laparoscopic robotic surgical dissection and minimally invasive treatment. Physicians also need to improve their skills in discussing the sexual implications of cancer and its treatment, as early diagnostic and therapeutic attention minimizes the impact on sexuality. Cancer survivors deserve and have the right to receive early competent psychosexual and medical help to attain a higher sexual QoL after the difficult and challenging path of fighting an intimate cancer.
References
1.
Graziottin A, Lukasiewicz M. Female sexual dysfunction and premature menopause. In: Lipshultz L, Pastuszek A, Perelman M, Giraldi AM, Buster J, editors. Sexual health in the couple: management of sexual dysfunction in men and women. New York: Springer; 2015.
2.
Lindau ST, Gavrilova N, Anderson D. Sexual morbidity in very long survivors of vaginal and cervical cancer: a comparison to national norms. Gynecol Oncol. 2007;106:413–8.CrossRefPubMedPubMedCentral
3.
Kennedy V, Abramsohn E, Makelarski J, et al. Can you ask? We just did! Assessing sexual function and concerns in patients presenting for initial gynecologic oncology consultation. Gynecol Oncol. 2015;131:119–24.CrossRef
4.
Bogani G, Serati M, Nappi R, et al. Nerve-sparing approach reduces sexual dysfunction in patients undergoing laparoscopic radical hysterectomy. J Sex Med. 2014;11:3012–20.CrossRefPubMed
5.
Lukasiewicz ME, Graziottin A. Women’ sexuality after gynecologic cancers. In: Studd J, Seang LT, Chervenak FA, editors. Current progress in obstetrics and gynaecology, vol. 2. 2nd ed. Mumbai: Kothari Medical; 2015.
6.
Juraskova I, Butow P, Robertson R, et al. Post-treatment sexual adjustment following cervical and endometrial cancer: a qualitative insight. Psychooncology. 2003;12:267–79.CrossRefPubMed
7.
Vichaya EG, Chiu GS, Krukowski K, et al. Mechanisms of chemotherapy-induced behavioral toxicities. Front Neurosci. 2015;9:131.CrossRefPubMedPubMedCentral
8.
Tierney DK. Sexuality: a quality-of-life issue for cancer survivors. Semin Oncol Nurs. 2008;24:71–9.CrossRefPubMed
9.
Graziottin A, Zanello PP. Pathogenic biofilms: their role in recurrent cystitis and vaginitis (with focus on D-mannose as a new prophylactic strategy). In: Studd J, Seang LT, Chervenak FA, editors. Current progress in obstetrics and gynaecology, vol. 2. 2nd ed. Mumbai: Kothari Medical; 2015.
10.
Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol. 2012;13:476–86.CrossRefPubMedPubMedCentral
11.
Sarrel PM. Effects of hormone replacement therapy on sexual psychophysiology and behavior in postmenopause. J Womens Health Gend Based Med. 2000;9 Suppl 1:S25–32.CrossRefPubMed
12.
Kotz K, Alexander JL, Dennerstein L. Estrogen and androgen hormone therapy and well-being in surgically postmenopausal women. J Womens Health (Larchmt). 2006;15:898–908.CrossRef
13.
Pluchino N, Drakopoulos P, Bianchi-Demicheli F, et al. Neurobiology of DHEA and effects on sexuality, mood and cognition. J Steroid Biochem Mol Biol. 2015;145:273–80.CrossRefPubMed
14.
Gold PW, Machado-Vieira R, Pavlatou MG. Clinical and biochemical manifestations of depression: relation to the neurobiology of stress. Neural Plast. 2015;2015:581976.PubMedPubMedCentral
15.
Schroder M, Mell LK, Hurteau JA, et al. Clitoral therapy device for treatment of sexual dysfunction in irradiated cervical cancer patients. Int J Radiat Oncol Biol Phys. 2005;61:1078–86.CrossRefPubMed
16.
Brotto J, Heiman J. Mindfulness in sex therapy: application for women with sexual difficulties following gynecological cancer. Sex Relat Ther. 2007;22:3–11.CrossRef