ACOG Menu

Treatment of Urogenital Symptoms in Individuals With a History of Estrogen-dependent Breast Cancer

  • Clinical Consensus CC
  • Number 2
  • December 2021

Number 2 (Replaces Committee Opinion Number 659, March 2016)

Committee on Clinical Consensus–Gynecology

This Committee Opinion was developed by the American College of Obstetricians and Gynecologists’ Committee on Clinical Consensus – Gynecology in collaboration with committee member Betty Suh-Burgmann, MD, and liaison Elizabeth Evans, MD


Summary: With an estimated 3.8 million breast cancer survivors in the United States, obstetrician–gynecologists often are on the front lines of addressing survivorship issues, including the hypoestrogenic-related adverse effects of cancer therapies or early menopause in survivors 1. Although systemic and vaginal estrogen are used widely for symptomatic relief of genitourinary syndrome of menopause in the general population, among individuals with a history of hormone-sensitive cancer, there is uncertainty about the safety of hormone-based therapy, leading many individuals with bothersome symptoms to remain untreated, with potential negative consequences on quality of life 2. An effective management strategy requires familiarity with a range of both hormonal and nonhormonal treatment options, knowledge about the pharmaceutical mechanisms of action, and the ability to tailor treatment based on individual risk factors. This clinical consensus document was developed using an a priori protocol in conjunction with two authors specializing in urogynecology and gynecologic oncology. This document has been updated to review the safety and efficacy of newer hormonal treatment options as well as nonhormonal modalities.


Background

Purpose

With an estimated 3.8 million breast cancer survivors in the United States, obstetrician–gynecologists often are on the front lines of addressing survivorship issues, including the hypoestrogenic-related adverse effects of cancer therapies or early menopause in survivors 1. The term genitourinary syndrome of menopause (GSM) will be used in this document to refer to a constellation of symptoms that relate to hypoestrogenic effects on the genital epithelium, such as genital dryness, burning, and irritation; potential downstream effects of vulvar and vaginal atrophy such as dyspareunia; urinary symptoms such as urgency or dysuria; and recurrent urinary tract infections 3. Although systemic and vaginal estrogen are used widely for symptomatic relief of GSM in the general population, among individuals with a history of hormone-sensitive cancer, there is uncertainty about the safety of hormone-based therapy, leading many individuals with bothersome symptoms to remain untreated, with potential negative consequences on quality of life 2. An effective management strategy requires familiarity with a range of both hormonal and nonhormonal treatment options Table 1, knowledge about the pharmaceutical mechanisms of action, and the ability to tailor treatment based on individual risk factors. This document has been updated to review the safety and efficacy of newer hormonal treatment options as well as nonhormonal modalities.

Treatment of Urogenital Symptoms in Individuals With a History of Estrogen-dependent Breast Cancer

The American College of Obstetricians and Gynecologists recognizes and supports the gender diversity of patients who seek obstetric and gynecologic care, including people who are cisgender, transgender, gender nonbinary, or otherwise gender expansive. Its goal is to use language that is inclusive of gender-diverse individuals. When describing research findings, this document uses the gender terminology reported by the investigators. Therefore, this document uses the terms “woman,” “women,” “patient,” and “individual.” The American College of Obstetricians and Gynecologists advocates for inclusive, thoughtful, affirming care, including the use of language that reflects a patient’s identity.

Epidemiology

On average, more than 250,000 women will be diagnosed with invasive breast cancer in the United States each year 4. The vast majority of cancers are hormone receptor–positive, with 80% demonstrating estrogen receptors and 65% demonstrating progesterone receptors. Although the overall median age at diagnosis is 62 years, 30% of cancers will be diagnosed in women younger than 50 years of age and 7% will be diagnosed in those younger than 40 years of age 5. Although the likelihood of having a hormone receptor negative breast cancer is higher for premenopausal individuals, the majority of breast cancers in premenopausal individuals are still hormone receptor–positive.

Endocrine therapy is a central component of treatment for those with hormone receptor–positive cancers. Following local management of early-stage cancers, most premenopausal individuals are treated with at least 5 years of tamoxifen, whereas postmenopausal individuals are commonly treated with up to 10 years of an aromatase inhibitor (AI). Tamoxifen acts as a selective estrogen antagonist in the breast, blocking estrogen at the receptor level, whereas AIs block peripheral estrogen biosynthesis from androstenedione and testosterone. Both forms of endocrine therapy are associated with GSM resulting from low estrogen levels. Although symptoms related to tamoxifen may be more pronounced owing to patient age, estrogen levels for those on AIs are lower than levels typically associated with menopause. Because of their mechanisms of action, the effects of exogenous estrogens on breast tissue would be expected to be blocked in those taking tamoxifen but not in those taking AIs.

Traditionally, oral or transdermal estrogen is used to treat systemic menopausal symptoms such as hot flushes and night sweats and for prevention of postmenopausal osteoporosis, whereas vaginal estrogen is used to treat urogenital symptoms. Although systemic estrogen also can be used to treat GSM, its use is generally considered contraindicated in individuals with a history of hormone receptor–positive breast cancer based on the potential for systemic estrogen to increase the risk of recurrence. Therefore, this document focuses on the use of vaginal estrogen and other local vaginal treatment options.

Health Inequities

Many of the data on the use of nonhormonal and hormonal approaches are overwhelmingly from White study participants. When demographic data were reported, most studies lacked racial and ethnic diversity, which could limit their generalizability. Although studies specifically evaluating disparities in the treatment of GSM in those with a history of breast cancer are lacking, the average age of diagnosis of breast cancer is slightly younger in Black women (56 years) when compared with White women (59 years) 6, suggesting that endocrine therapy may result in more severe symptoms among Black women, because younger women may experience a greater change in estrogen levels. Lower initiation and adherence rates to endocrine therapy have been reported among Black, Hispanic, and Asian women compared with White women; this is attributable to many potential factors, including lack of recommendation by health professionals, fear of adverse effects, and cost 7. In a survey study of 743 breast cancer survivors, 40% of those who discontinued endocrine therapy cited adverse effects as the main reason for stopping 8. Because adjuvant endocrine therapy has been shown to reduce the risk of breast cancer recurrence by approximately 40%, nonadherence due to adverse effects may lead to an increased risk of recurrence 9. Additionally, structural issues, such as health insurance, out-of-pocket cost of medications, and socioeconomic status, can affect access to available treatment options. Health care professionals who treat breast cancer survivors should be knowledgeable about adverse effects associated with endocrine therapy, as well as the systemic barriers that may prevent use and adherence, and take a proactive approach to mitigating potential negative effects of therapy on quality of life to support adherence to therapy. Studies on the treatment of GSM should strive to include a diverse cohort of participants to ensure that the lived experiences of all individuals with GSM are accounted for in the literature used to inform care.


Methods

This clinical consensus document was developed using an a priori protocol in conjunction with two authors specializing in urogynecology and gynecologic oncology. A full description of the Clinical Consensus methodology is published separately 10. The description below is specific to this Clinical Consensus.

Literature Search

The foundation for the evidence base were studies found by the 2000–2020 literature search. American College of Obstetricians and Gynecologists’ medical librarians searched in EMBASE, PubMed, and MEDLINE human-only studies written in English. The full reference list from ACOG Committee Opinion No. 659, The Use of Vaginal Estrogen in Women With a History of Estrogen-Dependent Breast Cancer, was provided to the authors for review and inclusion in the document. MeSH terms and keywords can be found in Appendix 1 (available online at http://links.lww.com/AOG/C482). Search terms for racial and ethnic disparities and implicit bias in the setting of vaginal estrogen treatment for women with estrogen-dependent breast cancer were incorporated into the literature review, and recommendations were drafted with the intent to promote health equity and reduce these disparities. A bridge literature search was completed in June 2021.

Study Selection

Qualifying studies that passed both title and abstract screen and full-text screen were conducted in countries ranked very high on the United Nations Human Development Index 11. Studies that focused on populations with cancer of any kind, as opposed to specifically breast cancer, were excluded. Only treatments for GSM commonly used in the United States were reviewed. Animal studies, basic science nonclinical studies, and opinion pieces were excluded. All other study designs were included in the evidence review. Studies that passed full-text screen by the authors were included in a summary evidence map (Appendix 2, available online at http://links.lww.com/AOG/C483).

Consensus Voting and Recommendation Development

At a meeting of the Committee on Clinical Consensus-Gynecology, a quorum of two thirds of eligible voting members was met and the committee held a formal vote for each proposed recommendation. All recommendation statements met or exceeded the 75% approval threshold required for consensus.


Consensus Recommendations and Discussion

Summary of Consensus Recommendations

Nonhormonal Approaches

  • Nonhormonal methods should be considered first-line treatment for urogenital symptoms in individuals with a history of estrogen-dependent breast cancer.

  • Gynecologists should be familiar with different nonhormonal treatment options because trials of multiple options may be needed to find effective treatment for any individual patient.

  • Nonhormonal treatments that have been reported to be effective in treating vulvovaginal symptoms include silicone-, polycarbophil-, and water-based lubricants; hyaluronic acid; polyacrylic acid; and vitamin E and D vaginal suppositories. There are insufficient data to indicate that one approach is superior to others.

Hormonal Approaches: Vaginal Estrogen

  • If nonhormonal treatments have failed to adequately address symptoms, after discussion of risks and benefits, low-dose vaginal estrogen may be used in individuals with a history of breast cancer, including those taking tamoxifen. For individuals taking aromatase inhibitors (AIs), low-dose vaginal estrogen can be used after shared decision making between the patient, gynecologist, and oncologist.

Dehydroepiandrosterone and Testosterone

  • If vaginal estrogen is not an option, vaginal dehydroepiandrosterone (DHEA) or testosterone may help with dyspareunia and improve vaginal tissue health.

Ospemifene/Selective Estrogen Receptor Modulators

  • Ospemifene, an orally administered selective estrogen receptor modulator (SERM), has been found to improve symptoms in a general population of menopausal individuals and may be considered as an option for individuals with a history of estrogen-dependent breast cancer. Although there is no indication that ospemifene is associated with increased risk of recurrence, long-term safety data are limited.

Nonhormonal Approaches

Nonhormonal methods should be considered first-line treatment for urogenital symptoms in individuals with a history of estrogen-dependent breast cancer.

Although hormonal-based treatments may be an option for individuals with a history of breast cancer, because many nonhormonal treatments are low-cost and low-risk, an initial trial of these options can be useful 12 13.

Gynecologists should be familiar with different nonhormonal treatment options because trials of multiple options may be needed to find effective treatment for any individual patient.

Patients’ concerns about GSM vary in terms of nature and severity, ranging from mild vulvovaginal irritation to dyspareunia related to introital discomfort or deep penetration, frequent urinary tract infection, and atrophy-related vaginal bleeding. Symptoms also may interact with other issues, such as overall health, nutrition, and psychosocial factors. Therefore, there is no “one-size-fits-all” treatment that will be appropriate for all individuals. Trials of different treatments may be needed before finding a therapy that is effective for and tolerated by an individual patient.

Nonhormonal treatments that have been reported to be effective in treating vulvovaginal symptoms include silicone-, polycarbophil-, and water-based lubricants; hyaluronic acid; polyacrylic acid; and vitamin E and D vaginal suppositories. There are insufficient data to indicate that one approach is superior to others.

Vaginal dryness and irritation, which often are contributing factors to dyspareunia, may be effectively treated with nonhormonal topical treatments. Several over-the-counter lubricants exist, and data demonstrate the effectiveness of vaginal moisturizers (eg, gels and creams) for the temporary relief of vaginal dryness, urogenital atrophy, and dyspareunia 14 15 16 17 18 19. In a randomized controlled trial of breast cancer survivors (N=45), a polycarbophil-based vaginal lubricant was similar to a water-based lubricant in treating vaginal dryness but was superior in reducing dyspareunia 20. A cohort study of sexually active postmenopausal breast cancer patients (N=38) found that a silicone-based lubricant provided greater symptomatic relief compared with water-based lubricant 21. More recently, lubricants containing polyacrylic acid or hyaluronic acid have become available. In a small trial of women taking tamoxifen (N=52), those randomized to polyacrylic acid reported a decrease in sexual dysfunction from 96% to 24%, compared with 88.9% to 55.6% for women using standard lubricant 22. Small studies have demonstrated relief of vaginal atrophy symptoms with the use of hyaluronic acid, particularly when dosed three to five times per week 23 24 25. Another small, randomized trial of breast cancer survivors (N=64) receiving tamoxifen and experiencing symptoms of vaginal atrophy found that both vitamin D and E suppositories were associated with improved vulvovaginal symptoms and lower vaginal pH compared with placebo 24. Oil-based lubricants should not be used with condoms, though most water-based and silicone-based lubricants can be used effectively with barrier methods 26. Patients should be counseled to review a product’s package insert before using with barrier methods.

The use of topical lidocaine may be particularly effective for dyspareunia related to introital pain. In a double-blind trial of 46 breast cancer survivors with severe penetrative dyspareunia, the use of 4% aqueous lidocaine applied to the introitus for 3 minutes before vaginal intercourse was associated with a reduction in dyspareunia of 88% compared with 38% for those randomized to saline placebo 27. Aqueous lidocaine also was helpful in reversing vestibular sensitivity in a similar patient population 28. Data are lacking on the efficacy of other nonhormonal topical treatments, such as formulations that combine known effective therapies with olive oil or oligopeptides and antioxidants 29 30, although, there have been no indications that such treatments cause harm.


Hormonal Treatment Options

If nonhormonal treatments have failed to adequately address symptoms, after discussion of risks and benefits, low-dose vaginal estrogen may be used in individuals with a history of breast cancer, including those taking tamoxifen. For individuals taking AIs, low-dose vaginal estrogen can be used after shared decision making between the patient, gynecologist, and oncologist.

Obstetrician–gynecologists can play an important role in the shared decision-making process by providing data on the safety of low-dose vaginal estrogen to patients and their medical oncologists. Clear communication with a patient’s medical oncologist, if possible, will support the shared decision-making process. Low-dose vaginal estrogen includes local (not systemic) products such as an estradiol-releasing vaginal ring, 10-microgram estradiol vaginal tablets or inserts, and comparable low doses of vaginal estrogen cream 31. To date, there is no evidence to indicate harm from these types of local treatments 32 33. Formulations that have been shown to be associated with serum estradiol levels of less than 20 pg/mL are 4-microgram estradiol insert, 7.5-microgram estradiol ring, and 10-microgram estradiol inserts and tablets 34. Other low-dose regimens included in this document’s review were estriol 0.25 mg twice a week and 12.5-microgram estradiol vaginal tablets twice a week. Dosing regimens were not provided in all studies. These low-dose vaginal estrogens have been reported to be highly effective at relieving symptoms of urogenital atrophy 35 36 37 38 39 40 compared with placebo 41 or water-based personal lubricant 19. Improved objective measures of vaginal health also have been demonstrated, including improved vaginal maturation index, pH, and vaginal cytology 19 41 42 43, as well as improved sexual function as measured by the Female Sexual Functioning Index, which assesses symptoms related to dyspareunia as well as other factors 41. However, there are insufficient data to establish one formulation of low-dose estrogen as superior to others. Additionally, although a common recommendation is to apply vaginal estrogen after vaginal intercourse to avoid potential exposure for a male partner, data are lacking on partner absorption 26.

Unlike tamoxifen, AIs do not block the effects of exogenous estrogens on breast tissue. With the concomitant use of both estrogen and an AI, there is the potential for elevated serum estrogen levels to stimulate estrogen receptors in breast tissue. However, when serum estradiol levels were evaluated in 10 studies, most demonstrated either only a transient increase (resolving within 12 weeks) or no increase at all in serum estrogen levels 35 37 38 40 41 42 44 45 46 47. Although the duration of use varied across studies, only one study reported sustained increases in serum estrogen levels in two of six participants at 7 and 12 weeks of use 37.

Regardless of serum estradiol levels, the main question is whether vaginal hormonal treatment increases the risk of breast cancer recurrence. Although studies that answer this question definitively are lacking, increased recurrence was not seen in seven studies 36 45 48 49 50 51 52 totaling more than 4,000 breast cancer survivors over a median follow-up of 2–7 years. These studies included women taking tamoxifen and women taking AIs and had varied follow-up time. Additionally, no change in breast density or Bi-RADS scores was observed in a cohort study of menopausal women after 1 year of estrogen use 53.

If vaginal estrogen is not an option, vaginal dehydroepiandrosterone (DHEA) or testosterone may help with dyspareunia and improve vaginal tissue health.

Prasterone is a vaginal DHEA insert (6.5 mg daily) that is approved by the U.S. Food and Drug Administration (FDA) for the treatment of moderate-to-severe dyspareunia due to menopause. Dehydroepiandrosterone can be converted to androstenedione, which, in turn, can be converted to estrogen through aromatization. Because estrogen is a metabolite of prasterone, there is concern about its use in individuals with a history of breast cancer. The product label notes that the use of exogenous estrogen is contraindicated in women with a known or suspected history of breast cancer and that manufacturers have not studied prasterone in this population 54. A randomized controlled trial of 464 women with a history of breast or gynecologic cancer compared both 6.5 mg and 3.25 mg of vaginal DHEA with plain moisturizer 55. Both the DHEA and moisturizer arms reported improvement in either dryness or dyspareunia, with no statistically significant difference between the arms. However, study participants receiving the higher (6.5-mg) dose reported better sexual health outcomes based on Female Sexual Functioning Index scores when compared with the 3.25-mg dose or moisturizer. No differences in adverse effects were reported among the three arms. Increases in serum estradiol were seen only among women receiving the 6.5-mg dose who were not on AI therapy. Of these 464 women, 345 contributed blood samples and 46 contributed vaginal cytology and pH values. Compared with plain moisturizer, DHEA resulted in increased DHEA-S and testosterone levels, although they were still in the lowest half or quartile of the postmenopausal range and was associated with greater improvement in vaginal cytology. Estrogen concentrations in women taking AIs were not changed 56.

Testosterone can help with proliferation of vaginal epithelium. Because the conversion of testosterone to estrogen is blocked in individuals using AIs, it is thought that testosterone may improve atrophy without interfering with the benefits of AIs. Though limited, there are promising data on the use of vaginal testosterone to improve symptoms of vulvovaginal atrophy, dyspareunia, and sexual dysfunction in those taking AIs 35 57 58 59 60 61, including data from two randomized clinical trials and two systematic reviews. In a 2017 randomized clinical trial, 69 postmenopausal women were randomized to a vaginal estrogen ring or intravaginal testosterone. Only four women in the intravaginal testosterone cream arm (12%) had persistent elevation in estrogen at the end of the 12-week study 35. A phase I/II study of 21 postmenopausal breast cancer patients with symptoms of vaginal atrophy taking AIs reports continued suppression of estrogen during 1 month of use of vaginal testosterone cream (either 300 micrograms or 150 micrograms per day) 62. Because most studies reviewed only 4 weeks of testosterone use, studies with longer duration are needed. The use of testosterone in women for this indication is considered off-label use.


Other Approaches to Treatment

Ospemifene, an orally administered selective estrogen receptor modulator, has been found to improve symptoms in a general population of menopausal individuals and may be considered as an option for individuals with a history of estrogen-dependent breast cancer. Although there is no indication that ospemifene is associated with increased risk of recurrence, long-term safety data are limited.

Ospemifene is a selective estrogen receptor modulator approved by the FDA for the treatment of postmenopausal vulvovaginal atrophy. In randomized placebo-controlled trials of more than 1,000 women from the general postmenopausal population, ospemifene use ranging from 12 weeks to 1 year in duration was associated with improved vaginal pH and vaginal tissue health as well as decreased patient reports of dyspareunia 63 64. Currently, the FDA-approved label includes a warning for its use in those with a history of breast cancer and states that, “it should not be used in women with known or suspected breast cancer” 65. In Europe, the drug is approved for use among women with a history of breast cancer who have completed all treatment 66. However, the FDA warning against its use in women with a history of breast cancer is controversial 67, because data published since ospemifene’s FDA approval have not demonstrated an increased risk of recurrence with its use 68 and may indicate higher patient satisfaction and adherence when compared with other local therapies 69. Furthermore, although ospemifene has an estrogen agonist effect on vaginal tissues as well as bone, available data indicate that it acts as an antagonist in breast tissue. Clinicians should discuss the label warning with patients and use clinical judgment to assess the appropriateness of its use.

Although ospemifene is not an estrogen, because of concerns about its potential estrogenic effects on the uterus, the label includes a black box warning about the potential increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. However, three double‐blind, placebo‐controlled clinical trials report that no cases of endometrial cancer or atypical endometrial hyperplasia were observed over a treatment period of 52 weeks 70.

Laser therapy.

There is emerging interest in treating GSM with laser therapy to potentially improve vaginal mucosal thickness, lubrication, and elasticity 71. The theory behind the mechanism of action is that fractional beams of light create small wounds in the epithelium and lamina propria that then lead to the stimulation of collagen, remodeling, and regeneration. It also is thought to increase blood flow to this area, improving tissue quality. Currently available data are based on largely observational studies with either small numbers of participants or limited follow-up 71 72; its efficacy has not been compared with other treatment options.

CO 2 and erbium laser therapy have been reported to improve vulvovaginal symptoms, including improved Vaginal Health Index measurements 73 74 75, subjective GSM symptoms 75 76 77 78 79 80, and sexual function 73 75 78 79 81 82 83 84. Laser therapy has shown promise in a research setting, with small trials demonstrating benefit, especially in the population of breast cancer survivors who may be hesitant to pursue hormonal therapy and often have more severe atrophic symptoms. However, consistent training and certification procedures for its use are lacking and concerns exist regarding the potential for scarring and long-term safety 85. Laser therapy is neither FDA-approved nor FDA-cleared for the treatment of symptoms related to menopause 86. It also is costly and not covered by insurance, making it inaccessible to many individuals. Additional research is warranted before recommending laser therapy for this indication.


Further Research

Available evidence suggest that low-dose vaginal estrogen is safe in individuals with a history of hormone receptor–positive breast cancer who are at low risk of recurrence. However, given the low incidence of recurrence as well as the extended length of follow-up needed to detect recurrence in this population, large prospective longitudinal studies of breast cancer survivors are needed to definitively address the question of whether these treatments are associated with any increased risk of recurrence. In addition, further research is needed on psychological interventions (eg, cognitive behavioral therapy and antidepressants), the safety and efficacy of newer agents such as ospemifene, and alternative treatments such as laser therapy to manage GSM in this population. Finally, because existing studies have evaluated the effectiveness of treatment among predominately White patients, additional studies are needed to understand whether the findings are generalizable to all racial and ethnic groups.


Appendices

  1. Literature Search Strategy: http://links.lww.com/AOG/C482

  2. Evidence Map: http://links.lww.com/AOG/C483


Conflict of Interest Statement

All ACOG committee members and authors have submitted a conflict of interest disclosure statement related to this published product. Any potential conflicts have been considered and managed in accordance with ACOG’s Conflict of Interest Disclosure Policy. The ACOG policies can be found on acog.org. For products jointly developed with other organizations, conflict of interest disclosures by representatives of the other organizations are addressed by those organizations. The American College of Obstetricians and Gynecologists has neither solicited nor accepted any commercial involvement in the development of the content of this published product.


References

  1. Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin 2019; 69: 363– 85. doi: 10.3322/caac.21565
    Article Locations:
    Article LocationArticle Location
  2. Nappi RE, Palacios S, Bruyniks N, Particco M, Panay N. The burden of vulvovaginal atrophy on women's daily living: implications on quality of life from a face-to-face real-life survey. EVES Study investigators. Menopause 2019; 26: 485– 91. doi: 10.1097/GME.0000000000001260
    Article Locations:
    Article LocationArticle Location
  3. Portman DJ, Gass ML. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and the North American Menopause Society. Vulvovaginal Atrophy Terminology Consensus Conference Panel. J Sex Med 2014; 11: 2865– 72. doi: 10.1111/jsm.12686
    Article Locations:
    Article Location
  4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70: 7– 30. doi: 10.3322/caac.21590
    Article Locations:
    Article Location
  5. National Cancer Institute. Cancer stat facts: female breast cancer. Accessed June 14, 2021. https://seer.cancer.gov/statfacts/html/breast.html
    Article Locations:
    Article Location
  6. Stapleton SM, Oseni TO, Bababekov YJ, Hung YC, Chang DC. Race/ethnicity and age distribution of breast cancer diagnosis in the United States. JAMA Surg 2018; 153: 594– 5. doi: 10.1001/jamasurg.2018.0035
    Article Locations:
    Article Location
  7. Livaudais JC, Hershman DL, Habel L, Kushi L, Gomez SL, Li CI, et al. Racial/ethnic differences in initiation of adjuvant hormonal therapy among women with hormone receptor-positive breast cancer. Breast Cancer Res Treat 2012; 131: 607– 17. doi: 10.1007/s10549-011-1762-1
    Article Locations:
    Article Location
  8. Friese CR, Pini TM, Li Y, Abrahamse PH, Graff JJ, Hamilton AS, et al. Adjuvant endocrine therapy initiation and persistence in a diverse sample of patients with breast cancer. Breast Cancer Res Treat 2013; 138: 931– 9. doi: 10.1007/s10549-013-2499-9
    Article Locations:
    Article Location
  9. Condorelli R, Vaz-Luis I. Managing side effects in adjuvant endocrine therapy for breast cancer. Expert Rev Anticancer Ther 2018; 18: 1101– 12. doi: 10.1080/14737140.2018.1520096
    Article Locations:
    Article Location
  10. Clinical consensus methodology. American College of Obstetricians and Gynecologists. Obstet Gynecol 2021; 138: 523– 26. doi: 10.1097/AOG.0000000000004520
    Article Locations:
    Article Location
  11. United Nations Development Programme. Human development index (HDI) . Accessed May 18, 2021. http://hdr.undp.org/en/content/human-development-index-hdi
    Article Locations:
    Article Location
  12. Derzko C, Elliott S, Lam W. Management of sexual dysfunction in postmenopausal breast cancer patients taking adjuvant aromatase inhibitor therapy. Curr Oncol 2007; 14( suppl 1): S20– 40. doi: 10.3747/co.2007.151
    Article Locations:
    Article Location
  13. Sussman TA, Kruse ML, Thacker HL, Abraham J. Managing genitourinary syndrome of menopause in breast cancer survivors receiving endocrine therapy. J Oncol Pract 2019; 15: 363– 70. doi: 10.1200/JOP.18.00710
    Article Locations:
    Article Location
  14. Kim YH, Park S, Lee M, Hahn S, Jeon MJ. Effect of a pH-balanced vaginal gel on dyspareunia and sexual function in breast cancer survivors who were premenopausal at diagnosis: a randomized controlled trial. Obstet Gynecol 2017; 129: 870– 6. doi: 10.1097/AOG.0000000000001988
    Article Locations:
    Article Location
  15. 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: 922– 7. doi: 10.1097/AOG.0b013e3182118790
    Article Locations:
    Article Location
  16. Seav SM, Dominick SA, Stepanyuk B, Gorman JR, Chingos DT, Ehren JL, et al. Management of sexual dysfunction in breast cancer survivors: a systematic review. Womens Midlife Health 2015; 1: 9. doi: 10.1186/s40695-015-0009-4
    Article Locations:
    Article Location
  17. Sinha A, Ewies AA. Non-hormonal topical treatment of vulvovaginal atrophy: an up-to-date overview. Climacteric 2013; 16: 305– 12. doi: 10.3109/13697137.2012.756466
    Article Locations:
    Article Location
  18. Chatsiproios D, Schmidts-Winkler IM, König L, Masur C, Abels C. Topical treatment of vaginal dryness with a non-hormonal cream in women undergoing breast cancer treatment - an open prospective multicenter study. PLoS One 2019; 14: e0210967. doi: 10.1371/journal.pone.0210967
    Article Locations:
    Article Location
  19. 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: 404– 12. doi: 10.3109/09513591003632258
    Article Locations:
    Article LocationArticle LocationArticle Location
  20. Loprinzi CL, Abu-Ghazaleh S, Sloan JA, vanHaelst-Pisani C, Hammer AM, Rowland KMJr, 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: 969– 73. doi: 10.1200/JCO.1997.15.3.969
    Article Locations:
    Article Location
  21. Hickey M, Marino JL, Braat S, Wong S. A randomized, double-blind, crossover trial comparing a silicone- versus water-based lubricant for sexual discomfort after breast cancer. Breast Cancer Res Treat 2016; 158: 79– 90. doi: 10.1007/s10549-016-3865-1
    Article Locations:
    Article Location
  22. Juliato PT, Rodrigues AT, Stahlschmidt R, Juliato CR, Mazzola PG. Can polyacrylic acid treat sexual dysfunction in women with breast cancer receiving tamoxifen? Climacteric 2017; 20: 62– 6. doi: 10.1080/13697137.2016.1258396
    Article Locations:
    Article Location
  23. Krychman M, Millheiser LS. Sexual health issues in women with cancer. J Sex Med 2013; 10( suppl 1): 5– 15. doi: 10.1111/jsm.12034
    Article Locations:
    Article Location
  24. Keshavarzi Z, Janghorban R, Alipour S, Tahmasebi S, Jokar A. The effect of vitamin D and E vaginal suppositories on tamoxifen-induced vaginal atrophy in women with breast cancer. Support Care Cancer 2019; 27: 1325– 34. doi: 10.1007/s00520-019-04684-6
    Article Locations:
    Article LocationArticle Location
  25. Carter J, Baser RE, Goldfrank DJ, Seidel B, Milli L, Stabile C, et al. A single-arm, prospective trial investigating the effectiveness of a non-hormonal vaginal moisturizer containing hyaluronic acid in postmenopausal cancer survivors. Support Care Cancer 2021; 29: 311– 22. doi: 10.1007/s00520-020-05472-3
    Article Locations:
    Article Location
  26. The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause 2020; 27: 976- 92. doi: 10.1097/GME.0000000000001609
    Article Locations:
    Article LocationArticle Location
  27. 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. doi: 10.1200/JCO.2014.60.7366
    Article Locations:
    Article Location
  28. Goetsch MF, Lim JY, Caughey AB. Locating pain in breast cancer survivors experiencing dyspareunia: a randomized controlled trial. Obstet Gynecol 2014; 123: 1231– 6. doi: 10.1097/AOG.0000000000000283
    Article Locations:
    Article Location
  29. 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: 2549– 58. doi: 10.1111/jsm.12156
    Article Locations:
    Article Location
  30. Amori P, Di Nardo V, Vitiello G, Franca K, Hercogova J, Wollina U, et al. Primavera: a new therapeutical approach to vulvo-vaginal atrophy. Dermatol Ther 2018; 31: e12678. doi: 10.1111/dth.12678
    Article Locations:
    Article Location
  31. Manson JE, Goldstein SR, Kagan R, Kaunitz AM, Liu JH, Pinkerton JV, et al. Why the product labeling for low-dose vaginal estrogen should be changed. Working Group on Women’s Health and Well-Being in Menopause. Menopause 2014; 21: 911– 6. doi: 10.1097/GME.0000000000000316
    Article Locations:
    Article Location
  32. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 2019; 394: 1159– 68. doi: 10.1016/S0140-6736(19)31709-X
    Article Locations:
    Article Location
  33. Lupo M, Dains JE, Madsen LT. Hormone replacement therapy: an increased risk of recurrence and mortality for breast cancer patients?. J Adv Pract Oncol 2015; 6: 322– 30. doi: 10.6004/jadpro.2015.6.4.3
    Article Locations:
    Article Location
  34. Crean-Tate KK, Faubion SS, Pederson HJ, Vencill JA, Batur P. Management of genitourinary syndrome of menopause in female cancer patients: a focus on vaginal hormonal therapy. Am J Obstet Gynecol 2020; 222: 103– 13. doi: 10.1016/j.ajog.2019.08.043
    Article Locations:
    Article Location
  35. Melisko ME, Goldman ME, Hwang J, De Luca A, Fang S, Esserman LJ, et al. Vaginal testosterone cream vs estradiol vaginal ring for vaginal dryness or decreased libido in women receiving aromatase inhibitors for early-stage breast cancer: a randomized clinical trial [published erratum appears in JAMA Oncol 2020;6:1473]. JAMA Oncol 2017; 3: 313– 9. doi: 10.1001/jamaoncol.2016.3904
    Article Locations:
    Article LocationArticle LocationArticle LocationArticle Location
  36. Decker DA, Pettinga JE, VanderVelde N, Huang RR, Kestin L, Burdakin JH. Estrogen replacement therapy in breast cancer survivors: a matched-controlled series. Menopause 2003; 10: 277– 85. doi: 10.1097/01.GME.0000061806.76067
    Article Locations:
    Article LocationArticle Location
  37. 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. doi: 10.1093/annonc/mdj127
    Article Locations:
    Article LocationArticle LocationArticle Location
  38. Pfeiler G, Glatz C, Königsberg 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: 339– 44. doi: 10.3109/13697137.2010.529967
    Article Locations:
    Article LocationArticle Location
  39. Buchholz S, Mögele M, Lintermans A, Bellen G, Prasauskas V, Ortmann O, et al. Vaginal estriol-lactobacilli combination and quality of life in endocrine-treated breast cancer. Climacteric 2015; 18: 252– 9. doi: 10.3109/13697137.2014.991301
    Article Locations:
    Article Location
  40. Donders G, Neven P, Moegele M, Lintermans A, Bellen G, Prasauskas V, et al. Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor(®)) 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: 371– 9. doi: 10.1007/s10549-014-2930-x
    Article Locations:
    Article LocationArticle Location
  41. Hirschberg AL, Sánchez-Rovira P, Presa-Lorite J, Campos-Delgado M, Gil-Gil M, Lidbrink E, et al. Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial. Menopause 2020; 27: 526– 34. doi: 10.1097/GME.0000000000001497
    Article Locations:
    Article LocationArticle LocationArticle LocationArticle Location
  42. Mazzarello S, Hutton B, Ibrahim MF, Jacobs C, Shorr R, Smith S, et al. Management of urogenital atrophy in breast cancer patients: a systematic review of available evidence from randomized trials. Breast Cancer Res Treat 2015; 152: 1– 8. doi: 10.1007/s10549-015-3434-z
    Article Locations:
    Article LocationArticle Location
  43. Donders G, Bellen G, Neven P, Grob P, Prasauskas V, Buchholz S, et al. Effect of ultra-low-dose estriol and lactobacilli vaginal tablets (Gynoflor®) on inflammatory and infectious markers of the vaginal ecosystem in postmenopausal women with breast cancer on aromatase inhibitors. Eur J Clin Microbiol Infect Dis 2015; 34: 2023– 8. doi: 10.1007/s10096-015-2447-1
    Article Locations:
    Article Location
  44. Pavlović RT, Janković SM, Milovanović JR, Stefanović SM, Folić MM, Milovanović OZ, et al. The safety of local hormonal treatment for vulvovaginal atrophy in women with estrogen receptor-positive breast cancer who are on adjuvant aromatase inhibitor therapy: meta-analysis. Clin Breast Cancer 2019; 19: e731– 40. doi: 10.1016/j.clbc.2019.07.007
    Article Locations:
    Article Location
  45. Harris BS, Bishop KC, Kuller JA, Ford AC, Muasher LC, Cantrell SE, et al. Hormonal management of menopausal symptoms in women with a history of gynecologic malignancy. Menopause 2020; 27: 243– 8. doi: 10.1097/GME.0000000000001447
    Article Locations:
    Article LocationArticle Location
  46. 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: 144– 8. doi: 10.1200/JOP.2011.000352
    Article Locations:
    Article Location
  47. Streff A, Chu-Pilli M, Stopeck A, Chalasani P. Changes in serum estradiol levels with Estring in postmenopausal women with breast cancer treated with aromatase inhibitors. Support Care Cancer 2021; 29: 187– 91. doi: 10.1007/s00520-020-05466-1
    Article Locations:
    Article Location
  48. Dew JE, Wren BG, Eden JA. A cohort study of topical vaginal estrogen therapy in women previously treated for breast cancer. Climacteric 2003; 6: 45– 52.
    Article Locations:
    Article Location
  49. Le Ray I, Dell'Aniello S, Bonnetain F, Azoulay L, Suissa S. 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. doi: 10.1007/s10549-012-2198-y
    Article Locations:
    Article Location
  50. Lyytinen H, Pukkala E, Ylikorkala O. Breast cancer risk in postmenopausal women using estrogen-only therapy. Obstet Gynecol 2006; 108: 1354– 60. doi: 10.1097/01.AOG.0000241091.86268.6e
    Article Locations:
    Article Location
  51. Crandall CJ, Hovey KM, Andrews CA, Chlebowski RT, Stefanick ML, Lane DS, et al. Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women's Health Initiative Observational Study. Menopause 2018; 25: 11– 20. doi: 10.1097/GME.0000000000000956
    Article Locations:
    Article Location
  52. O'Meara ES, Rossing MA, Daling JR, Elmore JG, Barlow WE, Weiss NS. Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality. J Natl Cancer Inst 2001; 93: 754– 62. doi: 10.1093/jnci/93.10.754
    Article Locations:
    Article Location
  53. Zuo SW, Wu H, Shen W. Vaginal estrogen and mammogram results: case series and review of literature on treatment of genitourinary syndrome of menopause (GSM) in breast cancer survivors. Menopause 2018; 25: 828– 36. doi: 10.1097/GME.0000000000001079
    Article Locations:
    Article Location
  54. Prasterone vaginal. In: Facts and comparisons . Accessed June 8, 2021. https://fco.factsandcomparisons.com/lco/action/doc/retrieve/docid/fc_dfc/6341402
    Article Locations:
    Article Location
  55. Barton DL, Sloan JA, Shuster LT, Gill P, Griffin P, Flynn K, et al. Evaluating the efficacy of vaginal dehydroepiandosterone for vaginal symptoms in postmenopausal cancer survivors: NCCTG N10C1 (Alliance). Support Care Cancer 2018; 26: 643– 50. doi: 10.1007/s00520-017-3878-2
    Article Locations:
    Article Location
  56. Barton DL, Shuster LT, Dockter T, Atherton PJ, Thielen J, Birrell SN, et al. Systemic and local effects of vaginal dehydroepiandrosterone (DHEA): NCCTG N10C1 (Alliance). Support Care Cancer 2018; 26: 1335– 43. doi: 10.1007/s00520-017-3960-9
    Article Locations:
    Article Location
  57. Bell RJ, Rizvi F, Islam RM, Davis SR. A systematic review of intravaginal testosterone for the treatment of vulvovaginal atrophy. Menopause 2018; 25: 704– 9. doi: 10.1097/GME.0000000000001052
    Article Locations:
    Article Location
  58. Lemke EA, Madsen LT, Dains JE. Vaginal testosterone for management of aromatase inhibitor-related sexual dysfunction: an integrative review. Oncol Nurs Forum 2017; 44: 296– 301. doi: 10.1188/17.ONF.296-301
    Article Locations:
    Article Location
  59. Davis SR, Robinson PJ, Jane F, White S, White M, Bell RJ. Intravaginal testosterone improves sexual satisfaction and vaginal symptoms associated with aromatase inhibitors. J Clin Endocrinol Metab 2018; 103: 4146– 54. doi: 10.1210/jc.2018-01345
    Article Locations:
    Article Location
  60. Dahir M, Travers-Gustafson D. Breast cancer, aromatase inhibitor therapy, and sexual functioning: a pilot study of the effects of vaginal testosterone therapy. Sex Med 2014; 2: 8– 15. doi: 10.1002/sm2.22
    Article Locations:
    Article Location
  61. Krychman ML, Stelling CJ, Carter J, Hudis CA. A case series of androgen use in breast cancer survivors with sexual dysfunction. J Sex Med 2007; 4: 1769– 74. doi: 10.1111/j.1743-6109.2007.00577.x
    Article Locations:
    Article Location
  62. 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. Oncologist 2011; 16: 424– 31. doi: 10.1634/theoncologist.2010-0435
    Article Locations:
    Article Location
  63. Di Donato V, Schiavi MC, Iacobelli V, D'oria O, Kontopantelis E, Simoncini T, et al. Ospemifene for the treatment of vulvar and vaginal atrophy: a meta-analysis of randomized trials. Part II: evaluation of tolerability and safety. Maturitas 2019; 121: 93– 100. doi: 10.1016/j.maturitas.2018.11.017
    Article Locations:
    Article Location
  64. Archer DF, Goldstein SR, Simon JA, Waldbaum AS, Sussman SA, Altomare C, et al. Efficacy and safety of ospemifene in postmenopausal women with moderate-to-severe vaginal dryness: a phase 3, randomized, double-blind, placebo-controlled, multicenter trial. Menopause 2019; 26: 611– 21. doi: 10.1097/GME.0000000000001292
    Article Locations:
    Article Location
  65. Ospemifene oral. In: Facts and comparisons . Accessed September 2, 2021. https://fco.factsandcomparisons.com/lco/action/doc/retrieve/docid/fc_dfc/5548487
    Article Locations:
    Article Location
  66. European Medicines Agency. Senshio. Annex I: summary of product characteristics . Accessed September 2, 2021. https://www.ema.europa.eu/en/documents/product-information/senshio-epar-product-information_en.pdf
    Article Locations:
    Article Location
  67. VA Pharmacy Benefits Management Services, Medical Advisory Panel, VISN Pharmacist Executives. Ospemifene (OSPHENA). National Drug Monograph . Accessed September 1, 2021. https://www.pbm.va.gov/PBM/clinicalguidance/drugmonographs/Osemifene_OSPHENA_Drug_Monograph.pdf
    Article Locations:
    Article Location
  68. Cai B, Simon J, Villa P, Biglia N, Panay N, Djumaeva S, et al. No increase in incidence or risk of recurrence of breast cancer in ospemifene-treated patients with vulvovaginal atrophy (VVA). Maturitas 2020; 142: 38– 44. doi: 10.1016/j.maturitas.2020.06.021
    Article Locations:
    Article Location
  69. Cagnacci A, Xholli A, Venier M. Ospemifene in the management of vulvar and vaginal atrophy: focus on the assessment of patient acceptability and ease of use. Patient Prefer Adherence 2020; 14: 55– 62. doi: 10.2147/PPA.S203614
    Article Locations:
    Article Location
  70. Constantine G, Graham S, Koltun WD, Kingsberg SA. Assessment of ospemifene or lubricants on clinical signs of VVA. J Sex Med 2014; 11: 1033– 41. doi: 10.1111/jsm.12428
    Article Locations:
    Article Location
  71. Jha S, Wyld L, Krishnaswamy PH. The impact of vaginal laser treatment for genitourinary syndrome of menopause in breast cancer survivors: a systematic review and meta-analysis. Clin Breast Cancer 2019; 19: e556– 62. doi: 10.1016/j.clbc.2019.04.007
    Article Locations:
    Article LocationArticle Location
  72. Athanasiou S, Pitsouni E, Douskos A, Salvatore S, Loutradis D, Grigoriadis T. Intravaginal energy-based devices and sexual health of female cancer survivors: a systematic review and meta-analysis. Lasers Med Sci 2020; 35: 1– 11. doi: 10.1007/s10103-019-02855-9
    Article Locations:
    Article Location
  73. Arêas F, Valadares AL, Conde DM, Costa-Paiva L. The effect of vaginal erbium laser treatment on sexual function and vaginal health in women with a history of breast cancer and symptoms of the genitourinary syndrome of menopause: a prospective study. Menopause 2019; 26: 1052– 8. doi: 10.1097/GME.0000000000001353
    Article Locations:
    Article LocationArticle Location
  74. Mothes AR, Runnebaum M, Runnebaum IB. Ablative dual-phase Erbium:YAG laser treatment of atrophy-related vaginal symptoms in post-menopausal breast cancer survivors omitting hormonal treatment. J Cancer Res Clin Oncol 2018; 144: 955– 60. doi: 10.1007/s00432-018-2614-8
    Article Locations:
    Article Location
  75. Salvatore S, Nappi RE, Casiraghi A, Ruffolo AF, Degliuomini R, Parma M, et al. Microablative fractional CO 2 laser for vulvovaginal atrophy in women with a history of breast cancer: a pilot study at 4-week follow-up . Clin Breast Cancer 2021 Feb 23 [Epub ahead of print]. doi: 10.1016/j.clbc.2021.01.006
    Article Locations:
    Article LocationArticle LocationArticle Location
  76. Gambacciani M, Levancini M. Vaginal erbium laser: the second generation thermotherapy for the genitourinary syndrome of menopause (GSM) in breast cancer survivors. A preliminary report of a pilot study. It J Gynaecol Obstet 2015; 27: N.1. doi: 10.14660/2385-0868-013
    Article Locations:
    Article Location
  77. Gambacciani M, Levancini M. Vaginal erbium laser as second-generation thermotherapy for the genitourinary syndrome of menopause: a pilot study in breast cancer survivors. Menopause 2017; 24: 316– 9. doi: 10.1097/GME.0000000000000761
    Article Locations:
    Article Location
  78. Pagano T, De Rosa P, Vallone R, Schettini F, Arpino G, De Placido S, 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. doi: 10.1097/GME.0000000000000672
    Article Locations:
    Article LocationArticle Location
  79. Pagano T, De Rosa P, Vallone R, Schettini F, Arpino G, Giuliano M, et al. Fractional microablative CO2 laser in breast cancer survivors affected by iatrogenic vulvovaginal atrophy after failure of nonestrogenic local treatments: a retrospective study [published erratum appears in Menopause 2018;25:1169]. Menopause 2018; 25: 657– 62. doi: 10.1097/GME.0000000000001053
    Article Locations:
    Article LocationArticle Location
  80. Quick AM, Zvinovski F, Hudson C, Hundley A, Evans C, Suresh A, et al. Fractional CO2 laser therapy for genitourinary syndrome of menopause for breast cancer survivors. Support Care Cancer 2020; 28: 3669– 77. doi: 10.1007/s00520-019-05211-3
    Article Locations:
    Article Location
  81. Gittens P, Mullen G. The effects of fractional microablative CO2 laser therapy on sexual function in postmenopausal women and women with a history of breast cancer treated with endocrine therapy. J Cosmet Laser Ther 2019; 21: 127– 31. doi: 10.1080/14764172.2018.1481510
    Article Locations:
    Article Location
  82. Pieralli A, Fallani MG, Becorpi A, Bianchi C, Corioni S, Longinotti M, et al. Fractional CO2 laser for vulvovaginal atrophy (VVA) dyspareunia relief in breast cancer survivors. Arch Gynecol Obstet 2016; 294: 841– 6. doi: 10.1007/s00404-016-4118-6
    Article Locations:
    Article Location
  83. Quick AM, Zvinovski F, Hudson C, Hundley A, Evans C, Stephens JA, et al. Patient-reported sexual function of breast cancer survivors with genitourinary syndrome of menopause after fractional CO2 laser therapy. Menopause 2021; 28: 642– 9. doi: 10.1097/GME.0000000000001738
    Article Locations:
    Article Location
  84. Veron L, Wehrer D, Annerose-Zéphir G, Suciu V, Delaloge S, Pistilli B, et al. Effects of local laser treatment on vulvovaginal atrophy among women with breast cancer: a prospective study with long-term follow-up. Breast Cancer Res Treat 2021; 188: 501– 9. doi: 10.1007/s10549-021-06226-3
    Article Locations:
    Article Location
  85. Donders GG, Ruban K, Bellen G, Grinceviciene S. Pharmacotherapy for the treatment of vaginal atrophy. Expert Opin Pharmacother 2019; 20: 821– 35. doi: 10.1080/14656566.2019.1574752
    Article Locations:
    Article Location
  86. U.S. Food and Drug Administration. Statement from FDA Commissioner Scott Gottlieb, M.D., on efforts to safeguard women’s health from deceptive health claims and significant risks related to devices marketed for use in medical procedures for “vaginal rejuvenation . Accessed September 13, 2021. https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-efforts-safeguard-womens-health-deceptive-health-claims
    Article Locations:
    Article Location

Published online on November 18, 2021.

Copyright 2021 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, posted on the internet, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher.

American College of Obstetricians and Gynecologists 409 12th Street SW, Washington, DC 20024-2188

Treatment of Urogenital Symptoms in Individuals With a History of Estrogen-dependent Breast Cancer. Clinical Consensus No. 2. American College of Obstetricians and Gynecologists. Obstet Gynecol 2021;138:950–60.

This information is designed as an educational resource to aid clinicians in providing obstetric and gynecologic care, and use of this information is voluntary. This information should not be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. It is not intended to substitute for the independent professional judgment of the treating clinician. Variations in practice may be warranted when, in the reasonable judgment of the treating clinician, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology. The American College of Obstetricians and Gynecologists reviews its publications regularly; however, its publications may not reflect the most recent evidence. Any updates to this document can be found on acog.org or by calling the ACOG Resource Center.

While ACOG makes every effort to present accurate and reliable information, this publication is provided “as is” without any warranty of accuracy, reliability, or otherwise, either express or implied. ACOG does not guarantee, warrant, or endorse the products or services of any firm, organization, or person. Neither ACOG nor its officers, directors, members, employees, or agents will be liable for any loss, damage, or claim with respect to any liabilities, including direct, special, indirect, or consequential damages, incurred in connection with this publication or reliance on the information presented.