Management of Breast Cancer Therapy–Related Sexual Dysfunction

October 15, 2017

This article reviews the mechanisms of sexual dysfunction that occur after breast cancer, offers some practical guidance on how to discuss this effectively with patients, and reviews the data and recommendations for optimizing management.

Sexual dysfunction is a prevalent concern among breast cancer survivors, and is often multifactorial in nature. Causes can be both physiologic and psychological; chemotherapy, endocrine therapy, and disfigurement from breast cancer surgery can all play a role. Sexual dysfunction can have a profound impact on quality of life and relationships and can also impact adherence to endocrine therapy. However, it can be a difficult topic for both patients and providers to bring up, and as a result, it is often inadequately addressed. Here, we will review the mechanisms of sexual dysfunction that occurs after breast cancer, offer some practical guidance on how to discuss this effectively with patients, and review the data and our recommendations for optimizing management.

Introduction

Sexual dysfunction after breast cancer is a well-known but often inadequately addressed problem. In addition to dealing with the stress surrounding a cancer diagnosis, women are often faced with multiple treatment-related side effects, some of which endure long after the completion of therapy. More than half of breast or gynecologic cancer survivors report severe, long-lasting sexual side effects[1] that often compromise physical and emotional well-being. Nausea, hair loss, and weight gain from chemotherapy; discomfort and physical changes from surgery; and postmenopausal symptoms and mood changes from endocrine therapy can negatively affect sexuality and body image and present ongoing challenges during treatment and survivorship.[2] A cross-sectional survey of women diagnosed with breast cancer prior to age 50 found premature menopause, fertility, sexual dysfunction, and body image to be the issues of greatest concern, along with frequently bothersome symptoms of hot flashes, vaginal dryness, and decreased libido.[3] Chemotherapy-related premature ovarian failure, biochemical ovarian suppression or oophorectomy, and endocrine therapy can all result in decreased levels of circulating estrogen and subsequent vaginal atrophy and dyspareunia. This premature loss of sexual function, in the setting of challenges surrounding body image, can be particularly devastating to women.[4] In our discussion, we will focus on the importance of managing symptoms such as dyspareunia as part of routine oncologic care.

Causes of Female Sexual Dysfunction

There are a number of physiologic causes of therapy-related sexual dysfunction in women. Endocrine therapy, in the form of tamoxifen or an aromatase inhibitor, is now recommended for 5 to 10 years in patients with hormone receptor–positive breast cancer, since it dramatically reduces the risk of recurrence and death from the disease.[5-7] However, these treatments, which significantly decrease circulating estrogen levels (aromatase inhibitors) and/or alter estrogen’s effect on target organs (tamoxifen), can have a sizable impact on sexual function. In one study, dyspareunia was reported by more than 50% of women receiving aromatase inhibitors and by 31.3% of those receiving tamoxifen.[8] Chemotherapy-related premature ovarian failure is also a concern, and is age-, dose-, and drug-dependent. Whether due to endocrine therapy or chemotherapy, low levels of circulating estrogen can lead to atrophic vaginitis, which can manifest as symptoms of dryness, pruritus, and dyspareunia.[9] One study found that sexual discomfort was significantly worse among women who had received chemotherapy than in women who received either tamoxifen or no therapy. The former group of women reported higher levels of sexual discomfort even years after completion of chemotherapy.[10] Aromatase inhibitors were found to cause more vaginal dryness than tamoxifen, likely due to the pro-estrogenic effect of tamoxifen on the vagina and endometrium.[9,11,12] Moreover, one study reported that longer duration of aromatase inhibitor use in hormone-sensitive breast cancers was associated with increasing reports of dyspareunia and vaginal dryness.[13] Now that there are data suggesting that a longer duration of treatment may be beneficial for some women (MA-17, aTTom, ATLAS), and that ovarian suppression with gonadotropin releasing hormone (GnRH) agonists or bilateral oophorectomy plus either tamoxifen or an aromatase inhibitor may be beneficial for younger women with more aggressive disease (SOFT, TEXT), addressing the problem of treatment-related dyspareunia becomes even more critical.[5-7,14,15]

In addition, it is important to recognize that some of the medications we use to treat side effects of breast cancer therapy can also have the unwanted side effect of sexual dysfunction. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are very effective means of reducing the hot flashes that can occur in women receiving anti-estrogen therapies, and many clinicians use these in their everyday practice for this purpose.[9,16] However, these drugs can have significant sexual side effects, including reduced libido, disrupted arousal, and anorgasmia.[17] These effects can be dose-dependent, so decreasing the dose or switching to a different SSRI or SNRI or to a different medication can be useful if sexual side effects occur.

Finally, the psychological impact of a cancer diagnosis and the challenges encountered during treatment play a large role in the symptoms experienced by women. In one analysis of the psychology behind sexual dysfunction and breast cancer, researchers identified desire, physiologic responses, satisfaction, and pain as the four primary constructs around which patients experienced difficulty.[18] Women may no longer view themselves as sexual beings in the face of fatigue, nausea, hair loss, weight gain, and removal of their breasts. This, in additional to physiologic effects such as lack of lubrication, can result in dyspareunia and significant sexual dysfunction.

The Importance of Addressing Sexual Dysfunction

Side effects are the most common reason for patient-reported nonadherence to medication. One study showed that up to 20% of breast cancer patients consider stopping or discontinue endocrine therapy because of side effects.[19] In order to comprehensively treat patients, physicians must become accustomed to addressing these symptoms. Physicians often fail to initiate conversations about such symptoms, and patients frequently feel uncomfortable broaching the topic of sexual functioning.[4] One study revealed that even when physicians did initiate conversations regarding sexuality, the discussion that ensued was often perceived as inadequate.[2] Office visit time constraints are a significant challenge. With increasing pressures to maximize patient volume, physicians have limited time per patient visit. Studies show that shorter office visits are associated with decreased attention to psychosocial matters and counseling, and with overall decreased patient satisfaction.[20,21] Thus, physicians must be mindful that these matters are not overlooked or dealt with too hastily. A formal screening tool for side effects could provide an efficient way to capture the relevant information and facilitate conversations early in the office visit. This would be a beneficial area of future research.

Assessing Sexual Dysfunction in the Clinic

When introducing treatment regimens such as chemotherapy or endocrine therapy, clinicians readily talk about side effects such as neuropathy, myelosuppression, bone density changes, and hot flashes-but vaginal dryness, dyspareunia, and decreased libido are less often discussed. Taking note of these potential side effects at the beginning of treatment opens the door for patients to report them later on, when they occur. Similarly, clinicians should also explain to patients the risk of sexual dysfunction when initiating therapy with an antidepressant to treat the side effects of anticancer therapy. It can also be beneficial to include sexual dysfunction on the review-of-systems questionnaire patients commonly fill out before they see the clinician at a routine follow-up visit. Once the issue has been raised, the cause or causes (vaginal dryness, psychological distress) can be determined through history and physical examination, and an optimal treatment plan can be developed.

KEY POINTS
  • Breast cancer therapy–related sexual dysfunction is common and stems from a variety of physiologic and psychological causes.
  • Common therapies for treatment-related sexual dysfunction include vaginal lubricants, topical lidocaine, and counseling.
  • It is important to assess for treatment-related sexual dysfunction both during and after treatment, and to tailor therapy to meet the individual needs of each patient.

What Options Are Available for Managing Dyspareunia?

There are multiple pharmacologic and nonpharmacologic options for the management of dyspareunia. Given the safety concerns regarding the use of hormonal therapy in women with estrogen receptor–positive breast cancer, nonhormonal options are the first-line treatment of hypoestrogenic sexual dysfunction.[22] Nonhormonal therapies such as vaginal moisturizers, vaginal lubrication, and topical lidocaine have proven to be effective for many women. One study demonstrated that the use of aqueous lidocaine 4% reduced vulvovestibular tenderness.[23] After liquid lidocaine use, 90% of breast cancer survivors reported more comfortable penetration and an overall decrease in sexual distress scores.[23,24] Fractional CO2 laser therapy, which delivers controlled energy to the vaginal tissue in order to induce collagen contraction, neocollaginosis, vascularization, and growth factor infiltration with the goal of returning the vaginal mucosa to its normal state, is a newer option-and an attractive one, given that it is nonhormonal and that results can be seen after just several sessions of therapy. Cost is a limiting factor for many women, however, since fractional CO2 laser therapy is FDA-approved but not covered by insurance, and the cost can be up to several thousand dollars out of pocket. There have been several published studies in breast cancer patients showing the benefits of fractional CO2 laser therapy,[25,26] so for patients who have the means and for whom dyspareunia is persistently distressing despite other less expensive therapies, this is a very reasonable option to consider.

Localized hormone therapy is a subject of significant debate. While vaginal estrogens in the form of a ring, pill, or cream have been shown to be the most effective agents for combating vaginal dryness, the associated risk factors in posttreatment populations have yet to be established. One cohort study assessing risk of breast cancer recurrence among tamoxifen-treated women found that overall, the use of local hormonal therapy was not associated with an increased risk of breast cancer recurrence (relative risk, 0.83; 95 % CI, 0.51–1.34). [16] However, some studies have demonstrated increases in plasma estradiol following the use of vaginal estradiol, raising concern for potential reactivation of tumor cells. These observations were reported in postmenopausal women treated with aromatase inhibitors.[13] Topical dehydroepiandrosterone has been studied as an alternative to current topical estrogen therapies. A recent study reported that with 12 weeks of use, there were significant improvements in sexual function, with no evidence of increased systemic estrogenic activity.[27] While current data do not show an increased risk of cancer recurrence among women who use vaginal hormonal therapy, the American Society of Clinical Oncology notes that the safety of vaginal estrogen is not well established and that the level of estrogen absorption is variable, raising concern in patients with a history of breast cancer.[28] Per American College of Obstetricians and Gynecologists guidelines, vaginal estrogen should only be considered once a patient has proved unresponsive to nonhormonal options.[22] We agree with this approach.

Communication and counseling should not be overlooked as treatment modalities. Analyses have shown that encouraging couples to focus on communication and problem-solving skills appears to decrease the likelihood of sexual dysfunction.[29] Counseling is often a useful alternative to pharmacologic interventions. In a review of nearly 400 patients in a cancer center who consulted a psychiatrist for sexual rehabilitation, about 64% reported notable improvement in sexual problems.[1] One small randomized trial in women receiving aromatase inhibitors evaluated the ability of early initiation of sexual counseling to minimize sexual dysfunction. The study found that at 6 months, women who received counseling reported less dyspareunia and less sexual distress compared with nontreatment groups.[30] Thus, relationship-building and counseling about sexual issues can be potentially effective therapy either alone or along with pharmacotherapy for alleviation of sexual dysfunction.

Conclusion

Given the large percentage of breast cancer patients who experience menopausal symptoms both during and after treatment, consistent assessment of these symptoms and their effect on patients’ quality of life should be a mainstay of routine care. The wide variation in symptoms, stemming from differences in age at diagnosis, menopausal status, and approach to treatment, makes individualized assessment essential. Each woman’s experience with breast cancer is unique, and thus her treatment should be tailored to meet her individual needs.[2] Addressing sexual dysfunction early and proactively may improve compliance with treatment and therefore treatment outcomes, and will certainly improve patients’ quality of life.

Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

References:

1. Schover LR. Counseling cancer patients about changes in sexual function. Oncology (Williston Park). 1999;13:1585-91; discussion 1591-2, 1595-6.

2. Male DA, Fergus KD, Cullen K. Sexual identity after breast cancer: sexuality, body image, and relationship repercussions. Curr Opin Support Palliat Care. 2016;10:66-74.

3. Avis NE, Crawford S, Manuel J. Psychosocial problems among younger women with breast cancer. Psychooncology. 2004;13:295-308.

4. Anllo LM. Sexual life after breast cancer. J Sex Marital Ther. 2000;26:241-8.

5. Davies C, Pan H, Godwin J, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381:805-16.

6. Francis PA, Regan MM, Fleming GF, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372:436-46.

7. Goss PE, Ingle JN, Pritchard KI, et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med. 2016;375:209-19.

8. Baumgart J, Nilsson K, Evers AS, et al. Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer. Menopause. 2013;20:162-8.

9. Hickey M, Saunders C, Partridge A, et al. Practical clinical guidelines for assessing and managing menopausal symptoms after breast cancer. Ann Oncol. 2008;19:1669-80.

10. Ganz PA, Desmond KA, Leedham B, et al. Quality of life in long-term, disease-free survivors of breast cancer: a follow-up study. J Natl Cancer Inst. 2002;94:39-49.

11. Cella D, Fallowfield LJ. Recognition and management of treatment-related side effects for breast cancer patients receiving adjuvant endocrine therapy. Breast Cancer Res Treat. 2008;107:167-80.

12. Fallowfield L, Cella D, Cuzick J, et al. Quality of life of postmenopausal women in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Adjuvant Breast Cancer Trial. J Clin Oncol. 2004;22:4261-71.

13. Moegele M, Buchholz S, Seitz S, Ortmann O. Vaginal estrogen therapy in postmenopausal breast cancer patients treated with aromatase inhibitors. Arch Gynecol Obstet. 2012;285:1397-402.

14. Gray R. aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol. 2013;31(suppl):abstr 5.

15. Regan MM, Francis PA, Pagani O, et al. Absolute benefit of adjuvant endocrine therapies for premenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer: TEXT and SOFT trials. J Clin Oncol. 2016;34:2221-31.

16. Le Ray I, Dell’Aniello S, Bonnetain F, et al. Local estrogen therapy and risk of breast cancer recurrence among hormone-treated patients: a nested case-control study. Breast Cancer Res Treat. 2012;135:603-9.

17. Seretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmacol. 2009;29:259-66.

18. Speer JJ, Hillenberg B, Sugrue DP, et al. Study of sexual functioning determinants in breast cancer survivors. Breast J. 2005;11:440-7.

19. Barron TI, Connolly R, Bennett K, et al. Early discontinuation of tamoxifen: a lesson for oncologists. Cancer. 2007;109:832-9.

20. Guy GP Jr, Richardson LC. Visit duration for outpatient physician office visits among patients with cancer. Am J Manag Care. 2012;18:SP49-56.

21. Howie JGR, Porter AMD, Forbes JF. Quality and the use of time in general practice: widening the discussion. BMJ. 1989;298:1008-10.

22. American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice, Farrell R. ACOG Committee Opinion No. 659: The Use of Vaginal Estrogen in Women With a History of Estrogen-Dependent Breast Cancer. Obstet Gynecol. 2016;127:e93-e96.

23. Goetsch MF, Lim JY, Caughey AB. Locating pain in breast cancer survivors experiencing dyspareunia: a randomized controlled trial. Obstet Gynecol. 2014;123:1231-6.

24. Goetsch MF, Lim JY, Caughey AB. A practical solution for dyspareunia in breast cancer survivors: a randomized controlled trial. J Clin Oncol. 2015;33:3394-400.

25. Pieralli A, Fallani MG, Becorpi A, et al. Fractional CO2 laser for vulvovaginal atrophy (VVA) dyspareunia relief in breast cancer survivors. Arch Gynecol Obstet. 2016;294:841-6.

26. Pagano T, De Rosa P, Vallone R, et al. Fractional microablative CO2 laser for vulvovaginal atrophy in women treated with chemotherapy and/or hormonal therapy for breast cancer: a retrospective study. Menopause. 2016;23:1108-13.

27. Barton DL, Sloan JA, Shuster LT, et al. Impact of vaginal dehydroepiandosterone (DHEA) on vaginal symptoms in female cancer survivors: trial N10C1 (Alliance). J Clin Oncol. 2014;32(suppl):abstr 9507.

28. Runowicz CD, Leach CR, Henry NL, et al. American Cancer Society/American Society of Clinical Oncology breast cancer survivorship care guideline. J Clin Oncol. 2016;34:611-35.

29. Kendall A, Dowsett M, Folkerd E, Smith I. Caution: vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol. 2006;17:584-7.

30. Advani P, Brewster AM, Baum GP, Schover LR. A pilot randomized trial to prevent sexual dysfunction in postmenopausal breast cancer survivors starting adjuvant aromatase inhibitor therapy. J Cancer Surviv. 2017;11:477-85.