- Open Access
Management of sexual dysfunction in breast cancer survivors: a systematic review
Women's Midlife Healthvolume 1, Article number: 9 (2015)
Female sexual dysfunction occurs frequently in midlife breast cancer survivors (BCS) and encompasses problems with sexual desire, interest, arousal, orgasm and genitopelvic pain. Although common, sexual problems are under-diagnosed and under-treated in BCS. The objective of this review was to assess primary studies that intervene on sexual dysfunction in BCS. In February 2015, PubMed, SCOPUS, CINAHL, COCHRANE and Web of Science databases were systematically searched for randomized controlled clinical trials (RCTs) of vaginal (lubricants, moisturizers, estrogens, dehydroepiandrosterone [DHEA], testosterone, vibrators, dilators), systemic (androgens, anti-depressants, flibanserin, ospemifene), physical therapy (physical activity, pelvic floor training), counseling and educational interventions on sexual function in BCS. Observational studies of vaginal interventions were also included due to the paucity of RCTs. The search yielded 1414 studies, 34 of which met inclusion criteria. Both interventions and outcomes, measured by 31 different sexual function scales, were heterogeneous, and therefore data were not pooled. The review found that regular and prolonged use of vaginal moisturizers was effective in improving vaginal dryness, dyspareunia, and sexual satisfaction. Educational and counseling interventions targeting sexual dysfunction showed consistent improvement in various aspects of sexual health. No consistent improvements in sexual health were observed with physical activity, transdermal testosterone or hot flash interventions. There was a lack of BCS-specific data on vaginal lubricants, vibrators, dilators, pelvic floor therapy, flibanserin or ospemifene. Overall, the quality of evidence for these studies was moderate to very low. Because each of the interventions with BCS data had limited efficacy, clinical trials to test novel interventions are needed to provide evidence-based clinical recommendations and improve sexual function in BCS.
In the United States, there are more than 2.3 million female cancer survivors who are younger than age 60; 40 % of these women are survivors of breast cancer . Most midlife breast cancer survivors (BCS) undergo surgery, chemotherapy, radiation and/or endocrine therapy for cancer treatment. Receiving a breast cancer diagnosis and undergoing associated treatments including long term endocrine therapy can impair sexual function via a number of mechanisms, including disrupting ovarian function, body image, intimacy and relationships [2–7]. In turn, impaired sexual function contributes to lower quality of life in survivorship [8, 9].
Female sexual dysfunction has been classified into three categories: sexual interest or arousal disorder, orgasmic disorder, and genitopelvic pain or penetration disorder. A women is diagnosed with sexual dysfunction if she experiences persistent symptoms that last at least six months and cause marked distress, as detailed in the Diagnostic and Statistical Manual 5th Edition (DSM-5)  (Table 1). A population-based cohort study of recently diagnosed BCS showed 65 % reported that they were sexually active; 52 % of sexually active women described problems with two or more areas of sexual function . At 5 and 10 years after cancer diagnosis, prevalence of sexual problems remained significant, 26 and 19 %, respectively . These findings that BCS are sexually active and experience sexual dysfunction that persists throughout survivorship have been replicated in multiple cohorts [9, 13–15].
Sexual health is often under-addressed in survivorship care, and only a minority of BCS receives information and education about sexual function from oncology professionals . Among primary care providers at a university-based medical center, 62 % self-reported never or rarely discussing sexual issues with cancer survivors . Providers who perceived having adequate preparedness to evaluate late effects or formal training in survivorship care were more likely to address sexual health considerations. Conversely, lack of knowledge in healthcare providers was a significant barrier to discussions on sex . Moreover, patients may be reluctant or embarrassed to raise sexual concerns with healthcare providers . Only 50 % of BCS thought their providers were knowledgeable about cancer care follow-up and even fewer (41 %) felt that their providers were equipped to treat their cancer therapy-related symptoms . Hence, disseminating evidence-based information on managing sexual concerns to healthcare providers is a critical aspect of improving sexual health care after breast cancer.
Multiple pharmacologic and behavioral treatments have been tested to improve sexual health after breast cancer. We present a systematic review of primary research on managing sexual dysfunction in breast cancer survivors to generate evidence-based content for improving knowledge on sexual health for BCS and their healthcare providers.
This systematic review was conducted in accordance with PRISMA guidelines . In February 2015, we systematically searched the following databases: PubMed (1966 – February 2015), SCOPUS (1966 – February 2015), CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1981 – February 2015), COCHRANE (all years), and Web of Science (1900 – February 2015). We screened the bibliographies of all included studies for additional references. We sought peer-reviewed articles examining interventions on sexual health among female BCS. We included studies on female breast cancer patients without age restriction and excluded studies on males, non-humans and other female cancer patients. We included studies on sexual dysfunction, including problems with dyspareunia, sexual pain, vaginismus, vaginal dryness, sexual arousal, desire, and orgasm. For types of interventions, we included vaginal (lubricants, moisturizers, estrogens, dehydroepiandrosterone [DHEA], testosterone, vibrators and dilators), systemic (androgens, anti-depressants, flibanserin, ospemifene), physical therapy (physical activity, pelvic floor training), counseling and educational interventions. We did not include studies on systemic estrogen interventions. For physical therapy, systemic, and counseling and educational interventions, we included only randomized controlled clinical trials (RCTs). We retained RCTs and observational studies (cohort and case control studies) on vaginal interventions due to the dearth of RCTs. We excluded qualitative studies and case reports. The final PubMed search strategy is detailed in the Appendix.
The primary outcome of this systematic review was sexual function. Measures of sexual function varied widely among studies and are summarized in Table 2.
Three review authors (SS, SD, IS) independently screened the titles and abstracts of all search citations using the inclusion and exclusion criteria. Discrepancies among authors were resolved via consensus. Two of the three review authors (SS, SD, or IS) independently abstracted data on included articles. Data extracted included participants, interventions, sexual health outcome measures, results, and risks of bias (randomization, allocation concealment, blinding, sample size and analysis approach).
Risk of bias for all included studies was assessed independently by two review authors (SD and IS) using the Cochrane risk of bias assessment tool . Discrepancies were resolved by discussion. Studies were evaluated for the following: selection bias (random sequence generation and allocation concealment); performance blinding (blinding of participants and personnel); detection bias (blinding of outcome assessment); attrition bias (incomplete outcome data); reporting bias (selective reporting); and other bias. Each bias criteria was assigned a high, low or unclear risk of bias rating. Additionally, we evaluated the quality of each study using the following GRADE criteria: study limitations (i.e., risk of bias); consistency of effect; imprecision; indirectness and publication bias. RCTs were first classified as high quality, and observational studies were first classified as low quality. All studies were downgraded in quality for any of the following problems: serious limitation to study quality; important inconsistency; uncertainty about directness; imprecise or sparse data; or high probability of reporting bias.
After searching PubMed (n = 637), SCOPUS (n = 665), CINAHL (n = 276), COCHRANE (n = 220) and Web of Science (n = 186) and hand picking (n = 14), 1984 articles were retrieved, leaving 1414 articles after removing duplicates. Forty-two full-text articles were accessed, from which 8 were excluded, leaving 34 articles included in this review. The PRISMA flow diagram details study selection results (Fig. 1). No article was excluded because of non-English language.
A total of 31 different sexual health outcome measures were used to assess intervention effects across the 34 papers (Table 2). The Female Sexual Function Index (n = 4 studies) and Cancer Rehabilitation Evaluation System (n = 3 studies) were the most commonly used measures. The Vaginal Maturation Index, Vaginal Health Index, and Sexual Activity Questionnaire were each used in 2 separate studies. All other outcome measures were used by single studies. Because of heterogeneity in both intervention and outcome measures, we were unable to pool estimates for a meta-analysis or derive strengths of recommendations based on the GRADE approach.
Vaginal products interventions
We searched for studies on vaginal lubricants, moisturizers, estrogens, DHEA, testosterone, vibrators and dilators. Eleven studies met inclusion criteria (Tables 3 and 4, Fig 2a). No studies were found on lubricants, DHEA, vibrators and dilators. There were 3 RCTs and 8 single-arm prospective cohorts with no controls. All participants had genitourinary symptoms, experienced ≥ 6 months of amenorrhea, and completed primary breast cancer treatment. The studies occurred in Australia, Belgium, Germany, Italy, Korea, and the United States. The polycarbophil-based moisturizer Replens® was tested in 4 studies involving 133 participants, one in combination with olive oil and pelvic floor muscle relaxation [23–26]; compounded testosterone cream was tested in 2 studies involving 34 participants [27, 28]; pH balanced lactic acid gel was used in 1 study of 98 participants ; and vaginal estrogens were used in 5 studies involving 47 participants [24, 30–33]. Outcomes included patient-reported vaginal symptoms, such as dryness, dyspareunia and itching, and vaginal exam-based pH and cytology.
In women using Replens®, vaginal dryness decreased in the first week of use , with significant additional improvement in dryness, dyspareunia, sexual satisfaction and frequency by 4 and 12 weeks of use [23, 25, 26]. Compared with local vaginal estrogens (estriol or estradiol), Replens® appeared less effective at decreasing vaginal symptoms and improving vaginal histology. However, women who used vaginal estrogens experienced an increase in their serum estradiol levels or decline in gonadotropins, both evidence of systemic absorption [24, 30–33]. At steady state, women on aromatase inhibitors using 25 microgram estradiol tablets twice weekly had low levels of serum estradiol (median 1.3 pg/mL) . However, 12 h after insertion of the tablet, median peak estradiol reached approximately 28 pg/mL . A pH-balanced gel (pH 4.0) decreased vaginal dryness and dyspareunia more than the placebo gel with a higher pH . Across products, vaginal irritation occurred in 12-50 % of participants, but whether this symptom persisted was not well described.
Two studies without control participants intervened with vaginal compounded testosterone in BCS on aromatase inhibitors [27, 28]. Compared to baseline measures, 4 weeks of vaginal testosterone improved all domains of the Female Sexual Function Inventory (FSFI) and vaginal atrophy symptoms. One study found 10 % (n = 2) of women had detectable serum estradiol levels after testosterone, though both estradiol levels were very low, <8 pg/mL .
Systemic therapy interventions
We sought studies using systemic androgens, anti-depressants, ospemifene and flibanserin to intervene on sexual function (Tables 5 and 6, Fig 2b). No studies on ospemifene or flibanserin were found. Three randomized, double-blind cross-over trials on androgens and anti-depressants were included. All participants completed primary cancer treatment. The studies were conducted in Brazil, Netherlands, and the United States. In the single study on applying daily testosterone cream to the skin for one month, testosterone in postmenopausal cancer survivors did not result in greater sexual desire, pleasure or function than placebo cream . This study accepted all cancer types, with 73 % of the 150 participants on tamoxifen or aromatase inhibitor, suggesting that they are breast cancer survivors. No increases in estradiol were noted while on testosterone cream, consistent with prior studies in women without history of breast cancer [35–40]. Two additional trials involving 115 participants intervened on hot flashes as the primary outcome with venlafaxine, clonidine or bupropion and examined if sexual function differed by these medications [41, 42]. There were no differences in sexual function between women treated with venlafaxine compared to clonidine nor with women treated with bupropion versus placebo [41, 42].
Physical therapy interventions
Three RCTs tested physical activity interventions on the primary outcomes of hot flashes, lymphedema, or physical strength and measured sexual health secondarily (Tables 5 and 6, Fig 2c). All participants completed primary breast cancer treatment. There were no studies on pelvic floor physical therapy. Included studies were conducted in the Netherlands, Sweden and United States. A home-based, self-directed exercise program intervened on 422 BCS and did not improve sexual habit, frequency or discomfort as measured by the Sexual Activity Questionnaire . In the two arms with cognitive behavioral therapy, with or without exercise, there was a modest effect on improving sexual health habit at 24 weeks when compared to waitlist controls. Strength training over one year in the second trial of 295 participants was associated with a small improvement in self-perceptions of appearance and sexuality . Finally, a general physical training and coping skills intervention in 199 cancer survivors (80 % with breast cancer) did not directly address sexual health and did not find change in frequency of sexual problems .
Counseling and educational interventions
Seventeen RCTs delivered counseling and/or educational interventions and measured sexual health outcomes in a total of 2,494 participants (Tables 5 and 6, Fig 2d). Participants were studied at various stages of cancer treatment. Studies were conducted in Australia, Finland, Greece, Korea, Netherlands, United Kingdom, and United States. Nine studies targeted sexual health as the primary outcome [46–54]. There was considerable heterogeneity on intervention and outcome measurements. Twelve studies intervened on the individual, while 5 studies intervened on the couple. The majority delivered in-person interventions, many with additional telephone-support [46, 53, 55–58]. Two recent studies tested web-based interventions [46, 54]. Counseling strategies varied widely, from problem-solving therapy to sexual therapy to cognitive behavioral therapy. Most interventions were delivered by nurses, psychologists, social workers, or peers.
Several findings were consistent. In studies designed specifically to intervene on sexual health, improvements in sexual function were observed in the intervention group compared to controls [46, 48–51], but effect sizes were generally modest and of unclear clinical significance. For example, a 4-month trial tested behavioral and non-estrogen replacement pharmacologic interventions on menopausal symptoms in 76 BCS . The intervention group received individualized plans of education, counseling, pharmacologic and/or behavioral interventions, psychosocial support, and referrals compared to controls who underwent usual care. Sexual function was measured by the CARES Sexual Summary Scale, which is scored from 0 to 4 (higher score indicating more severe problems). The mean score change of the intervention group (0.46, 95 % CI 0.30–0.62) was statistically significantly larger than that of the control group (0.11, 95 % CI −0.16 to 0.38), p = 0.03, but clinical relevance is unclear. Most studies intervening on general psychosocial health, rather than targeting sexual health, did not appear to improve sexual function [55, 58–60]. Researchers who undertook group therapy interventions reported difficulties with attendance and higher dropout rates [49, 51]. Couple-based therapy incorporated counseling on cancer, sexual health, and communication and consistently improved various aspects of sexual function, most frequently sexual satisfaction [47, 50, 61].
The majority of BCS experience sexual problems in survivorship, most commonly vaginal and vulvar dryness. Despite the significant population of BCS and high prevalence of sexual problems, the number of RCTs intervening on sexual health was limited. This review summarized evidence for BCS across all ages, because trials in midlife BCS were few. Results showed significant evidence for regular use of vaginal moisturizers to improve dryness, dyspareunia, and sexual satisfaction. Uncontrolled studies with vaginal estradiol, estriol or testosterone also improved vaginal symptoms, but showed systemic absorption. Educational and counseling interventions, particularly those targeting sexual dysfunction, improved various aspects of sexual health. No consistent improvements in sexual health were observed with physical activity, transdermal testosterone or hot flash interventions. Overall for most included studies, the quality of evidence by GRADE criteria was moderate to low.
Vulvovaginal symptoms occur in 20 to 50 % of healthy women of midlife and older as a result of estrogen deprivation . BCS are at heightened risk of these symptoms because chemotherapy, oophorectomy and/or endocrine therapies further decrease estrogen exposure. The clinical trial data show improvements in vaginal dryness, dyspareunia, sexual satisfaction and frequency, and vaginal pH with regular use at least 2-3 times weekly of a polycarbophil-based vaginal moisturizer. Compliance for at least twelve weeks is important, because major symptom gains occurred between 1-3 months and recur after stopping use, similar to data in the general population . Vulvovaginal symptom relief from regular use of other moisturizers is likely, and pH balance in products may be important [23, 29]. Among available vaginal moisturizers, BCS should consider preferentially using products with evidence of efficacy.
Use of minimally absorbed local vaginal estrogens and androgens provide vaginal symptom relief, with local estrogens appearing more effective than non-hormonal moisturizers [24, 64]. Even at low doses, estradiol tablets and creams and compounded testosterone are systemically absorbed [24, 28, 30–33]. Unfortunately, there are no clinical trial data on adverse breast cancer outcomes with extended use. Nor are there studies in BCS that compare 7, 10 and 25 micrograms of vaginal estradiol for symptom control and systemic absorption. Whether risk of breast cancer recurrence or death would be higher in estrogen-responsive tumors is also unknown. As local estrogens and androgens are not FDA-approved for use in BCS, these medications are prescribed off-label and use requires careful discussion between BCS and their healthcare providers.
There was a lack of evidence to support incorporating systemic interventions or physical therapy into the treatment paradigm for sexual dysfunction. The single trial on transdermal testosterone did not demonstrate greater sexual desire compared to the placebo cream after 1 month of use . These findings stand in contrast to several trials in women without prior breast cancer in which androgen therapy improved sexual desire, potentially because these trials were longer in duration (12-24 weeks) and provided supplemental estrogen [35–40]. Notably, there were no clinical trials on treating sexual dysfunction related to serotonin receptor uptake inhibitors in BCS.
Multiple counseling and educational strategies, particularly those targeting sexual dysfunction, have been shown to improve sexual health in BCS. Marriage and family therapists, sex therapists, sexual counselors or psychologists offer counseling interventions. With the aid of online resources, BCS can look for providers who are appropriately educated, credentialed or have significant prior experience with sexual health after cancer. Excellent online resources are found on sites for the American Association of Sexuality Educators, Counselors, and Therapists, the International Society for the Study of Women’s Sexual Health, and the American Cancer Society. A number of investigators have designed educational interventions using printed materials, CDs, and websites for content with healthcare provider or peer support [46, 48, 52–54]. This approach is important to study further, as it has the potential advantage of being delivered remotely to extend access to BCS who do not have specialized care locally.
The strength of this review is the systematic approach to identifying and grading current evidence on sexual health interventions specific to breast cancer survivors. This approach enabled us to identify the gaps in data. Several interventions that have shown promise in women without a history of breast cancer have not undergone clinical trials in BCS. These include ospemifene and systemic DHEA for the treatment of vulvovaginal symptoms and flibanserin for the treatment of arousal and sexual interest disorders [65, 66]. The primary limitation was heterogeneity of interventions and outcome measures that restricted the ability to pool data from studies of limited sample size. A recent systematic review sought to evaluate the psychometric properties of sexual dysfunction screening tools and the extent to which they measure DSM-5 aspects of sexual dysfunction for BCS . The review found 31 different scales measuring sexual function, of which the Arizona Sexual Experience Scale, Female Sexual Function Index, and Sexual Problems Scale were determined to meet criteria for acceptable psychometric properties while incorporating DSM-5 areas of sexual dysfunction. Future studies in BCS should carefully consider these outcome measures in study design.
This review demonstrated that current evidence on interventions for improving sexual interest, orgasm and genitopelvic pain in BCS of midlife is limited in quantity and moderate to low in quality. From these data, we recommend prolonged and regular use of non-hormonal vaginal moisturizers to alleviate vulvar and vaginal dryness symptoms and dyspareunia. We also recommend seeking educational and counseling interventions. A number of online resources on sexual health after breast cancer may be useful for BCS and their providers (Table 7). Because each of these interventions have limited efficacy, clinical trials to test novel interventions such as ospemifene are needed in breast cancer survivors.
American Cancer Society. Cancer Treatment and Survivorship Facts & Figs. 2014-2015. Atlanta: American Cancer Society; 2014.
Baron RH, Kelvin JF, Bookbinder M, Cramer L, Borgen PI, Thaler HT. Patients’ sensations after breast cancer surgery. A pilot study. Cancer Pract. 2000;8(5):215–22.
Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol. 1996;14(5):1718–29.
Onen Sertoz O, Elbi Mete H, Noyan A, Alper M, Kapkac M. Effects of surgery type on body image, sexuality, self-esteem, and marital adjustment in breast cancer: a controlled study. Turkish J Psychiatry. 2004;15(4):264–75.
Pelusi J. Sexuality and body image. Cancer Nurs. 2006;29(2 Suppl):32–8.
Wilmoth MC, Ross JA. Women’s perception. Breast cancer treatment and sexuality. Cancer Pract. 1997;5(6):353–9.
Hawkins Y, Ussher J, Gilbert E, Perz J, Sandoval M, Sundquist K. Changes in sexuality and intimacy after the diagnosis and treatment of cancer: the experience of partners in a sexual relationship with a person with cancer. Cancer Nurs. 2009;32(4):271–80. doi:10.1097/NCC.0b013e31819b5a93.
Ganz PA, Rowland JH, Meyerowitz BE, Desmond KA. Impact of different adjuvant therapy strategies on quality of life in breast cancer survivors. Recent Results Cancer Res. 1998;152:396–411.
Ganz PA, Rowland JH, Desmond K, Meyerowitz BE, Wyatt GE. Life after breast cancer: understanding women’s health-related quality of life and sexual functioning. J Clin Oncol. 1998;16(2):501–14.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Association; 2013.
Fobair P, Stewart SL, Chang S, D’Onofrio C, Banks PJ, Bloom JR. Body image and sexual problems in young women with breast cancer. Psycho-oncology. 2006;15(7):579–94. doi:10.1002/pon.991.
Bloom JR, Stewart SL, Oakley-Girvan I, Banks PJ, Shema S. Quality of life of younger breast cancer survivors: persistence of problems and sense of well-being. Psycho-oncology. 2012;21(6):655–65. doi:10.1002/pon.1965.
Burwell SR, Case LD, Kaelin C, Avis NE. Sexual problems in younger women after breast cancer surgery. J Clin Oncol. 2006;24(18):2815–21. doi:10.1200/jco.2005.04.2499.
Avis NE, Crawford S, Manuel J. Quality of life among younger women with breast cancer. J Clin Oncol. 2005;23(15):3322–30. doi:10.1200/jco.2005.05.130.
Kornblith AB, Powell M, Regan MM, Bennett S, Krasner C, Moy B, et al. Long-term psychosocial adjustment of older vs younger survivors of breast and endometrial cancer. Psycho-oncology. 2007;16(10):895–903. doi:10.1002/pon.1146.
Flynn KE, Reese JB, Jeffery DD, Abernethy AP, Lin L, Shelby RA, et al. Patient experiences with communication about sex during and after treatment for cancer. Psycho-oncology. 2012;21(6):594–601. doi:10.1002/pon.1947.
Park ER, Bober SL, Campbell EG, Recklitis CJ, Kutner JS, Diller L. General internist communication about sexual function with cancer survivors. J Gen Intern Med. 2009;24 Suppl 2:S407–11. doi:10.1007/s11606-009-1026-5.
Ussher JM, Perz J, Gilbert E, Wong WK, Mason C, Hobbs K, et al. Talking about sex after cancer: a discourse analytic study of health care professional accounts of sexual communication with patients. Psychol Health. 2013;28(12):1370–90. doi:10.1080/08870446.2013.811242.
Bachmann GA, Leiblum SR, Grill J. Brief sexual inquiry in gynecologic practice. Obstet Gynecol. 1989;73(3 Pt 1):425–7.
Mao JJ, Bowman MA, Stricker CT, DeMichele A, Jacobs L, Chan D, et al. Delivery of survivorship care by primary care physicians: the perspective of breast cancer patients. J Clin Oncol. 2009;27(6):933–8. doi:10.1200/jco.2008.18.0679.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7), e1000097. doi:10.1371/journal.pmed.1000097.
Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi:10.1136/bmj.d5928.
Loprinzi CL, Abu-Ghazaleh S, Sloan JA, Van Haelst-Pisani C, Hammer AM, Rowland Jr KM, et al. Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer. J Clin Oncol. 1997;15(3):969–73.
Biglia N, Peano E, Sgandurra P, Moggio G, Panuccio E, Migliardi M, et al. Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study. Gynecol Endocrinol. 2010;26(6):404–12. doi:10.3109/09513591003632258.
Gelfand MM, Wendman E. Treating vaginal dryness in breast cancer patients: results of applying a polycarbophil moisturizing gel. J Women’s Health. 1994;3(6):427–34.
Juraskova I, Jarvis S, Mok K, Peate M, Meiser B, Cheah BC, et al. The acceptability, feasibility, and efficacy (phase I/II study) of the OVERcome (Olive Oil, Vaginal Exercise, and MoisturizeR) intervention to improve dyspareunia and alleviate sexual problems in women with breast cancer. J Sex Med. 2013;10(10):2549–58. doi:10.1111/jsm.12156.
Dahir M, Travers-Gustafson D. Breast cancer, aromatase inhibitor therapy, and sexual functioning: a pilot study of the effects of vaginal testosterone therapy. Sexual Med. 2014;2(1):8–15. doi:10.1002/sm2.22.
Witherby S, Johnson J, Demers L, Mount S, Littenberg B, Maclean CD, et al. Topical testosterone for breast cancer patients with vaginal atrophy related to aromatase inhibitors: a phase I/II study. The Oncologist. 2011;16(4):424–31. doi:10.1634/theoncologist.2010-0435.
Lee YK, Chung HH, Kim JW, Park NH, Song YS, Kang SB. Vaginal pH-balanced gel for the control of atrophic vaginitis among breast cancer survivors: a randomized controlled trial. Obstet Gynecol. 2011;117(4):922–7. doi:10.1097/AOG.0b013e3182118790.
Pfeiler G, Glatz C, Konigsberg R, Geisendorfer T, Fink-Retter A, Kubista E, et al. Vaginal estriol to overcome side-effects of aromatase inhibitors in breast cancer patients. Climacteric. 2011;14(3):339–44. doi:10.3109/13697137.2010.529967.
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(4):584–7. doi:10.1093/annonc/mdj127.
Donders G, Neven P, Moegele M, Lintermans A, Bellen G, Prasauskas V, et al. Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor((R))) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study. Breast Cancer Res Treat. 2014;145(2):371–9. doi:10.1007/s10549-014-2930-x.
Wills S, Ravipati A, Venuturumilli P, Kresge C, Folkerd E, Dowsett M, et al. Effects of vaginal estrogens on serum estradiol levels in postmenopausal breast cancer survivors and women at risk of breast cancer taking an aromatase inhibitor or a selective estrogen receptor modulator. J Oncol Pract. 2012;8(3):144–8. doi:10.1200/jop.2011.000352.
Barton DL, Wender DB, Sloan JA, Dalton RJ, Balcueva EP, Atherton PJ, et al. Randomized controlled trial to evaluate transdermal testosterone in female cancer survivors with decreased libido; North Central Cancer Treatment Group protocol N02C3. J Natl Cancer Inst. 2007;99(9):672–9. doi:10.1093/jnci/djk149.
Shifren JL, Braunstein GD, Simon JA, Casson PR, Buster JE, Redmond GP, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med. 2000;343(10):682–8. doi:10.1056/nejm200009073431002.
Goldstat R, Briganti E, Tran J, Wolfe R, Davis SR. Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women. Menopause. 2003;10(5):390–8. doi:10.1097/01.gme.0000060256.03945.20.
Braunstein GD, Sundwall DA, Katz M, Shifren JL, Buster JE, Simon JA, et al. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Arch Intern Med. 2005;165(14):1582–9. doi:10.1001/archinte.165.14.1582.
Buster JE, Kingsberg SA, Aguirre O, Brown C, Breaux JG, Buch A, et al. Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Obstet Gynecol. 2005;105(5 Pt 1):944–52. doi:10.1097/01.AOG.0000158103.27672.0d.
Simon J, Braunstein G, Nachtigall L, Utian W, Katz M, Miller S, et al. Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. J Clin Endocrinol Metab. 2005;90(9):5226–33. doi:10.1210/jc.2004-1747.
Nathorst-Boos J, Floter A, Jarkander-Rolff M, Carlstrom K, Schoultz B. Treatment with percutanous testosterone gel in postmenopausal women with decreased libido--effects on sexuality and psychological general well-being. Maturitas. 2006;53(1):11–8. doi:10.1016/j.maturitas.2005.01.002.
Nunez GR, Pinczowski H, Zanellato R, Tateyama L, Schindler F, Fonseca F, et al. Bupropion for control of hot flashes in breast cancer survivors: a prospective, double-blind, randomized, crossover, pilot phase II trial. Journal of Pain and Symptom Management. 2013;45(6):969–79. doi:10.1016/j.jpainsymman.2012.06.011.
Buijs C, Mom CH, Willemse PH, Marike Boezen H, Maurer JM, Wymenga AN, et al. Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: a double-blind, randomized cross-over study. Breast Cancer Res Treat. 2009;115(3):573–80. doi:10.1007/s10549-008-0138-7.
Duijts SFA, Stolk-Vos AC, Oldenburg HSA, Van Beurden M, Aaronson NK. Characteristics of breast cancer patients who experience menopausal transition due to treatment. Climacteric. 2011;14(3):362–8. doi:10.3109/13697137.2011.557163.
Speck RM, Gross CR, Hormes JM, Ahmed RL, Lytle LA, Hwang WT, et al. Changes in the Body Image and Relationship Scale following a one-year strength training trial for breast cancer survivors with or at risk for lymphedema. Breast Cancer Res Treat. 2010;121(2):421–30. doi:10.1007/s10549-009-0550-7.
Berglund G, Bolund C, Gustafsson U, Sjoden P. A randomized study of a rehabilitation program for cancer patients: the ‘starting again’ group. Psycho-oncology. 1994;3:109–20.
Anderson DJ, Seib C, McCarthy AL, Yates P, Porter-Steele J, McGuire A, et al. Facilitating lifestyle changes to manage menopausal symptoms in women with breast cancer: a randomized controlled pilot trial of The Pink Women’s Wellness Program. Menopause. 2015. doi:10.1097/gme.0000000000000421.
Baucom DH, Porter LS, Kirby JS, Gremore TM, Wiesenthal N, Aldridge W, et al. A couple-based intervention for female breast cancer. Psycho-oncology. 2009;18(3):276–83. doi:10.1002/pon.1395.
Ganz PA, Greendale GA, Petersen L, Zibecchi L, Kahn B, Belin TR. Managing menopausal symptoms in breast cancer survivors: results of a randomized controlled trial. J Natl Cancer Inst. 2000;92(13):1054–64.
Jun EY, Kim S, Chang SB, Oh K, Kang HS, Kang SS. The effect of a sexual life reframing program on marital intimacy, body image, and sexual function among breast cancer survivors. Cancer Nurs. 2011;34(2):142–9. doi:10.1097/NCC.0b013e3181f1ab7a.
Kalaitzi C, Papadopoulos VP, Michas K, Vlasis K, Skandalakis P, Filippou D. Combined brief psychosexual intervention after mastectomy: effects on sexuality, body image, and psychological well-being. J Surg Oncol. 2007;96(3):235–40. doi:10.1002/jso.20811.
Rowland JH, Meyerowitz BE, Crespi CM, Leedham B, Desmond K, Belin TR, et al. Addressing intimacy and partner communication after breast cancer: a randomized controlled group intervention. Breast Cancer Res Treat. 2009;118(1):99–111. doi:10.1007/s10549-009-0398-x.
Schover LR, Jenkins R, Sui D, Adams JH, Marion MS, Jackson KE. Randomized trial of peer counseling on reproductive health in African American breast cancer survivors. J Clin Oncol. 2006;24(10):1620–6. doi:10.1200/jco.2005.04.7159.
Schover LR, Rhodes MM, Baum G, Adams JH, Jenkins R, Lewis P, et al. Sisters Peer Counseling in Reproductive Issues After Treatment (SPIRIT): a peer counseling program to improve reproductive health among African American breast cancer survivors. Cancer. 2011;117(21):4983–92. doi:10.1002/cncr.26139.
Schover LR, Yuan Y, Fellman BM, Odensky E, Lewis PE, Martinetti P. Efficacy trial of an Internet-based intervention for cancer-related female sexual dysfunction. J Natl Compr Cancer Netw. 2013;11(11):1389–97.
Allen SM, Shah AC, Nezu AM, Nezu CM, Ciambrone D, Hogan J, et al. A problem-solving approach to stress reduction among younger women with breast carcinoma: a randomized controlled trial. Cancer. 2002;94(12):3089–100. doi:10.1002/cncr.10586.
Germino B, Mishel M, Crandell J, Porter L, Blyler D, Jenerette C, et al. Outcomes of an uncertainty management intervention in younger African American and Caucasian breast cancer survivors. Oncol Nurs Forum. 2013;40(1):82–92. doi:10.1188/13.ONF.82-92.
Marcus AC, Garrett KM, Cella D, Wenzel L, Brady MJ, Fairclough D, et al. Can telephone counseling post-treatment improve psychosocial outcomes among early stage breast cancer survivors? Psycho-oncology. 2010;19(9):923–32. doi:10.1002/pon.1653.
Salonen P, Tarkka MT, Kellokumpu-Lehtinen PL, Koivisto AM, Aalto P, Kaunonen M. Effect of social support on changes in quality of life in early breast cancer patients: a longitudinal study. Scandinavian Journal of Caring Sciences. 2013;27(2):396–405. doi:10.1111/j.1471-6712.2012.01050.x.
Greer S, Moorey S, Baruch JD, Watson M, Robertson BM, Mason A, et al. Adjuvant psychological therapy for patients with cancer: a prospective randomised trial. BMJ. 1992;304(6828):675–80.
Vos PJ, Garssen B, Visser AP, Duivenvoorden HJ, de Haes HC. Psychosocial intervention for women with primary, non-metastatic breast cancer: a comparison between participants and non-participants. Psychother Psychosom. 2004;73(5):276–85. doi:10.1159/000078844.
Christensen D. Postmastectomy couple counseling: an outcome study of a structured treatment protocol. J Sex Marital Therapy. 1983;9(4):266–75. doi:10.1080/00926238308410913.
North Amer Menopause S. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause. 2013;20(9):888–902. doi:10.1097/gme.0b013e3182a122c2.
Bygdeman M, Swahn ML. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas. 1996;23(3):259–63.
Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, et al. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol. 2014;124(6):1147–56. doi:10.1097/aog.0000000000000526.
Portman DJ, Bachmann GA, Simon JA. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause. 2013;20(6):623–30. doi:10.1097/gme.0b013e318279ba64.
Tan O, Bradshaw K, Carr BR. Management of vulvovaginal atrophy-related sexual dysfunction in postmenopausal women: an up-to-date review. Menopause. 2012;19(1):109–17. doi:10.1097/gme.0b013e31821f92df.
Bartula I, Sherman KA. Screening for sexual dysfunction in women diagnosed with breast cancer: systematic review and recommendations. Breast Cancer Res Treat. 2013;141(2):173–85. doi:10.1007/s10549-013-2685-9.
McGahuey CA, Gelenberg AJ, Laukes CA, Moreno FA, Delgado PL, McKnight KM, et al. The Arizona Sexual Experience Scale (ASEX): reliability and validity. J Sex Marital Ther. 2000;26(1):25–40.
Mathias C, Athanazio RA, Braghiroli MI, et al. Use of the Arizona Sexual Experience Scale (ASEX) in the evaluation of sexual dysfunction in Brazilian cancer patients. [in Spanish]. J Bras Psiquiatr. 2005;54:216–20.
Hormes JM, Lytle LA, Gross CR, Ahmed RL, Troxel AB, Schmitz KH. The body image and relationships scale: development and validation of a measure of body image in female breast cancer survivors. J Clin Oncol. 2008;26(8):1269–74. doi:10.1200/jco.2007.14.2661.
Schag CAC, Heinrich RL. Cancer Rehabilitation Evaluation System (CARES) manual. CARES Consultants: Santa Monica; 1988.
Clayton AH, McGarvey EL, Clavet GJ. The Changes in Sexual Functioning Questionnaire (CSFQ): development, reliability, and validity. Psychopharmacol Bull. 1997;33(4):731–45.
Derogatis LR. The Derogatis Interview for Sexual Functioning (DISF/DISF-SR): an introductory report. J Sex Marital Ther. 1997;23(4):291–304. doi:10.1080/00926239708403933.
Sprangers MA, Groenvold M, Arraras JI, Franklin J, te Velde A, Muller, M et al. The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: first results from a three-country field study. J Clin Oncol. 1996;14(10):2756–68.
Wiegel M, Meston C, Rosen R. The female sexual function index (FSFI): cross-validation and development of clinical cutoff scores. J Sex Marital Ther. 2005;31(1):1–20. doi:10.1080/00926230590475206.
Fallowfield LJ, Leaity SK, Howell A, Benson S, Cella D. Assessment of quality of life in women undergoing hormonal therapy for breast cancer: validation of an endocrine symptom subscale for the FACT-B. Breast Cancer Res Treat. 1999;55(2):189–99.
Waring EM, Reddon JR. The measurement of intimacy in marriage: the Waring Intimacy Questionnaire. J Clin Psychol. 1983;39(1):53–7.
Ware Jr JE, The SCD, MOS. 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–83.
Rosen RC, Lobo RA, Block BA, Yang HM, Zipfel LM. Menopausal Sexual Interest Questionnaire (MSIQ): a unidimensional scale for the assessment of sexual interest in postmenopausal women. J Sex Marital Ther. 2004;30(4):235–50. doi:10.1080/00926230490422340.
Ganz PA, Day R, Ware Jr JE, Redmond C, Fisher B. Base-line quality-of-life assessment in the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial. J Natl Cancer Inst. 1995;87(18):1372–82.
McHorney CA, Rust J, Golombok S, Davis S, Bouchard C, Brown C, et al. Profile of Female Sexual Function: a patient-based, international, psychometric instrument for the assessment of hypoactive sexual desire in oophorectomized women. Menopause. 2004;11(4):474–83.
Derogatis LR. The psychosocial adjustment to illness scale (PAIS). J Psychosom Res. 1986;30(1):77–91.
Norton R. Measuring marital quality: a critical look at the dependent variable. J Marriage Fam. 1983;45:141–51.
Thirlaway K, Fallowfield L, Cuzick J. The Sexual Activity Questionnaire: a measure of women’s sexual functioning. Quality Life Res. 1996;5(1):81–90.
Taylor JF, Rosen RC, Leiblum SR. Self-report assessment of female sexual function: psychometric evaluation of the brief index of sexual functioning for women. Arch Sex Behav. 1994;23(6):627–643.
Greene JG. Constructing a standard climacteric scale. Maturitas. 1998;29(1):25–31.
Crane R. Sexual satisfaction scale. 1977.
Kim SNCSB, Kang HS. Development of sexual satisfaction measurement tool. J Korean Acad Nurs. 1997;27(4):753–64.
Andersen BL, Cyranowski JM. Women’s sexual self schema. J Pers Soc Psychol. 1994;67:1079–100.
Speroff L. Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms. Obstet Gynecol. 2003;102(4):823–34.
Davila GW, Singh A, Karapanagiotou I, Woodhouse S, Huber K, Zimberg S, et al. Are women with urogenital atrophy symptomatic? Am J Obstet Gynecol. 2003;188(2):382–8.
Rioux JE, Devlin C, Gelfand MM, Steinberg WM, Hepburn DS. 17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause. 2000;7(3):156–61.
Bachmann G. Urogenital ageing: an old problem newly recognized. Maturitas. 1995;22(Suppl):S1–5.
Bachmann GA, Notelovitz M, Gonzalez SJ, Thompson C, Morecraft BA. Vaginal dryness in menopausal women: clinical characteristics and nonhormonal treatment. Clinical Practice Sexuaity. 1991;7(9):1–8.
Hustin J, Van den Eynde JP. Cytologic evaluation of the effect of various estrogens given in postmenopause. Acta Cytol. 1977;21(2):225–8.
Scott JL, Halford WK, Ward, BG. United we stand? The effects of a couple-coping intervention on adjustment to early stage breast or gynecologicalcancer. J Consult Clin Psychol. 2004;72(6):1122-35.
This study was financially supported by the Breast Cancer Research Program 120500-PFT-11-008-01-CPPB, HD-058799-01. The funding organization was not involved in the study design, data collection, data analyses, or writing of the manuscript for publication.
The authors declare that they have no competing interests.
SS, SD, BS and IS conducted the initial search and screen for inclusion papers. IS and SS drafted the Summary of Studies and Outcomes Tables. IS and SD assessed risk of bias for each study. All authors were involved in drafting the manuscript or revising it critically for intellectual accuracy. All authors read and approved the final manuscript.
PubMed Search Strategy
(("Clinical Trial"[Publication Type] OR "Comparative Study"[Publication Type]) OR ("Phase I Clinical Trial" OR "Phase II Clinical Trial" OR "Phase III Clinical Trial" OR "Phase IV Clinical Trial" OR "Controlled Clinical Trial" OR "Multicenter Study" OR "Observational Study" OR "Randomized Controlled Trial" OR "Pragmatic Clinical Trial" OR "Comparative Study")).
AND (("Breast Neoplasms"[Mesh] NOT "Breast Neoplasms, Male"[Mesh]) OR ("Breast cancer" OR "Breast Neoplasms")).
AND (("Sexual Dysfunctions, Psychological/prevention and control"[Mesh] OR "Sexual Dysfunctions, Psychological/rehabilitation"[Mesh] OR "Sexual Dysfunctions, Psychological/therapy"[Mesh] OR "Sexual Dysfunction, Physiological/prevention and control"[Mesh] OR "Sexual Dysfunction, Physiological/rehabilitation"[Mesh] OR "Sexual Dysfunction, Physiological/therapy"[Mesh] OR "Vaginal Creams, Foams, and Jellies"[Mesh] OR "Biofeedback, Psychology"[Mesh] OR "Cognitive Therapy"[Mesh] OR "Psychotherapy"[Mesh] OR "Sex Counseling"[Mesh] OR "Patient Education as Topic"[Mesh] OR "Testosterone/therapy"[Mesh] OR "Antidepressive Agents"[Mesh]) OR ("vaginal lubricant" OR "vaginal moisturizer" OR "pelvic floor muscle relaxation" OR "pelvic floor physical therapy" OR "pelvic floor muscle training" OR "biofeedback" OR "vaginal dilator" OR "biofeedback" OR "cognitive behavioral therapy" OR ("sex" AND "therapy") OR "psychotherapy" OR "sex counseling" OR "patient education" OR "testosterone" OR "antidepressant" OR "treatment" OR "flibanserin" OR "ospemifene" OR "vibrator" OR "vaginal dilator" OR "DHEA")).
AND (("Sexual Dysfunction, Physiological"[Mesh] OR "Interpersonal Relations"[Mesh] OR "Sexual Behavior"[Mesh] OR "Vaginismus"[Mesh] OR "Coitus"[Mesh] OR "Libido"[Mesh] OR "Orgasm"[Mesh]) OR ("dyspareunia" OR "coitus" OR "coital frequency" OR "intercourse frequency" OR "vaginal dryness" OR "sexual lubrication" OR "vulvovaginal atrophy" OR "libido" OR "sexual function" OR "sexual dysfunction" OR "sexual interest" OR "sexual desire" OR "sexual arousal" OR "orgasm" OR "sexual pleasure" OR "sexual dissatisfaction" OR "sex" OR "intimacy" OR "sexual desire disorder" OR "sexual arousal disorder" OR "orgasmic disorder" OR "sexual pain disorder")).