Sex after breast cancer: a forgotten burden? Erin MacLellan PGY-4 Obstetrics and Gynecology McMaster University

Transcription

1 ex after breast cancer: a forgotten burden? Erin MacLellan PGY-4 Obstetrics and Gynecology McMaster University

2 Objectives Review significance of the problem of vaginal atrophy in survivors of breast cancer Raise topic of hypoactive sexual desire disorder (HDD) Discuss treatment options including pharmacological and non-pharmacological choices Recommend strategies to overcome barriers in dialogue about sexual dysfunction with health care providers

3 Overview Background Female pelvic anatomy Estrogen physiology and urogenital atrophy Hormonal therapy Non-hormonal therapy Conclusions

4 Background Treatment of breast cancer often involves the combination of chemo and endocrine therapy which induces menopause in more than 80% of women in the first year after diagnosis. Many breast cancer patients receive multi-modality therapy including surgery, chemotherapy, and hormonal therapy which cure disease or prolong life. Among breast cancer survivors, vaginal dryness and loss of libido represent some of the most challenging long term side effects of breast cancer treatment.

5 Cycle of pain

6 Background In the setting of estrogen deprivation, the mucosal and stromal tissues of the vagina, urethra, and trigone of the bladder undergo atrophy, resulting in decreased tissue elasticity and fluid secretion. This may lead to symptomatic vaginal dryness and irritation as well as dyspareunia. Estrogen deprivation also leads to an elevation in vaginal ph which may increase the risk of vaginal and urinary tract infections.

7 Female pelvic anatomy

8 Location of estrogen receptors

9 nd the onset of these physical findings isvariable. The ss of rugosity is due to the breakdown of the collagen upport of the vaginal epithelium. Collagen turnover is creased in aging women without hormone therapy, nd these changes may be of importance in vaginal rolapse 3 5. Effects of estrogen on vaginal epithelium with the developing vaginal anlage in the embryo. urethra has high levels of estrogen receptors becaus is derived from the same embryonic origin as the d vagina 1.Atrophy of the urethra with a relative incr in urethral epithelial transitional cells, and a co sponding decrease in intermediate and superfi

10 Ovariectomy in younger breast cancer patients Psychological symptoms (13.25 vs 8.52; P = 0.009), vasomotor symptoms (4.00 vs 2.74; P = 0.035), and sexual dysfunction scores (2.25 vs 1.58; P = 0.031) were significantly higher in breast cancer women with ovariectomy compared with breast cancer women without ovariectomy exual feelings for partners (P = 0.02) and sexual frequency (P = 0.01) were less in women with ovariectomy compared with women without ovariectomy. Feelings of physical health, attractiveness, overall appearance, and satisfaction were significantly lower in ovariectomized women (P < 0.05). ayakhot P et al. Potential adverse impact on ovariectomy on physical and psychological function of younger women with breast cancer. Menopause 2011;18(7):

11 Prevalence of hypoactive sexual desire disorder (HDD) Most common sexual complaint in women Persistently or recurrently deficient sexual fantasies and desire for sexual activity Result in marked distress or interpersonal difficulty Controlled cross-sectional study evaluated long-term frequency in younger patients with breast cancer Ochsenkuhn R et al. Menopausal status in breast cancer patients with past chemotherapy determines longterm HDD. J exual Med 2011;8:

12 Prevalence of HDD Examine effect of past chemo and adjuvant endocrine therapy on sexual desire on young women with breast cancer University of Munich 34 patients with breast cancer treated with surgery/chemo/endocrine therapy 13 patients with benign breast disease served as controls tandardized questionnaire Ochsenkuhn R et al. Menopausal status in breast cancer patients with past chemotherapy determines longterm HDD. J exual Med 2011;8:

13 Prevalence of HDD key results Chemotherapy alone does not significantly impair long-term sexual desire and function, compared to a control group with comparable breast surgery but no malignant disease or systemic therapy There is a statistically significant association between menopausal status and mean IDI-F scores In conclusion, chemotherapy in young breast cancer patients does not significantly impair long-term sexual desire as compared to patients with benign breast disease, unless permanent menopause is induced.

14 Hormonal options

15 Hormonal options

16 Low-dose vaginal estrogens tarting hormone therapy necessitates a discussion of the treatment s risks, benefits, and alternatives. Cancer survivors, particularly women who have had breast cancer, are typically reluctant to try hormones because of their concerns about the potential cancer risk. Cancer survivors, particularly women with non-hormonedependent cancer, can be appropriate candidates for vaginal estrogens in combination with non-hormonal strategies.

17 Low-dose vaginal estrogens for urogenital atrophy Eighteen patients receiving estriol cream 0.25 mg (n = 10) or estradiol tablets 12.5 mg (n = 8) twice/week for 12 weeks were evaluated and compared with eight patients treated with polycarbophil-based moisturizer 2.5 g twice/week. everity of vaginal atrophy was assessed using subjective [Vaginal ymptoms core (V), Profile of Female exual Function (PFF)] and objective [Vaginal Health Index (VHI), Karyopycnotic Index (KI)] evaluations afety was evaluated by measuring endometrial thickness and serum sex hormones levels. Biglia N et al. Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study. Gynecol Endocrinol 2010; 26(6):

18 Low-dose vaginal estrogens for urogenital atrophy Endometrial thickness did not significantly change during treatment, with a mean increase of 0.5 mm after 3 months of vaginal ET. Did not find any significant modification of hormone serum values at the end of the treatment period as compared to baseline. E2 levels increased by a mean 3.5 pg/ml in women who received vaginal estriol cream and by a mean of 2.7 pg/ml in the group treated with micronized estradiol tablets. Biglia N et al. Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study. Gynecol Endocrinol 2010; 26(6):

19 nature [22]. M any trials have evaluated the absorption of vaginal estrogen preparations at conventional doses in postmenopausal women, showing that it is strictly dose-dependent and is maximal in the first days of treatment, when the vaginal mucosa is thin and atrophic [ 23 25]. Recent studies have suggested that it might be possible to lower the vaginal estrogen dose to one which does not significantly increase systemic levels of estrogens, but is still effective on women receiving E2 tablets or E3 cream at low dose, without difference between the two preparations. A further improvement was seen at the end of 3 months of therapy. In women receiving vaginal moisturizer, although a transient benefit on symptoms related to vaginal atrophy was recorded after 4 weeks, thereafter the effect was lost. T he objective assessment of vaginal health conducted by study investigators (VH I ), evaluating the appearance of the vaginal mucosa, confirmed the favourable effect of the two Low-dose vaginal estrogens for urogenital atrophy T able III. Changes in the PFF in patients treated with vaginal estrogen therapy and vaginal moisturizer at the end of the treatment period as compared to baseline. PFF variables T ime interval Vaginal estrogen therapy (%) p-value Vaginal moisturizer (%) p-value exual desire Basal 12 weeks " # exual arousal Basal 12 weeks Orgasm Basal 12 weeks " # exual pleasure Basal 12 weeks " " exual concerns Basal 12 weeks " " exual responsiveness Basal 12 weeks " # exual self-image Basal 12 weeks " " Global satisfaction with sexuality Basal 12 weeks " " Arrows going upward indicate better sexual function. Biglia N et al. Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study. Gynecol Endocrinol 2010; 26(6):

20 Low-dose vaginal estrogens for urogenital atrophy The preliminary results of this study show that low-dose vaginal ET, both with E3 cream or E2 tablets, is effective in relieving vaginal atrophy in postmenopausal breast cancer survivors. Data are lacking about the absorption and the efficacy of low-dose vaginal ET in breast cancer survivors; theoretically, if systemic absorption of estrogens is minimal, any increase of breast cancer recurrence should be unlikely. Biglia N et al. Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study. Gynecol Endocrinol 2010; 26(6):

21 Limited data Retrospective, case-controlled or cohort studies hort follow-up mall numbers 6-75 women using vaginal estrogens Population often combined with oral HRT Conclusion: ERT does not have a significant adverse effect on cancer outcome; no increased risk of recurrence or death

22 What about tamoxifen use? In women taking tamoxifen following breast cancer, there is very little concern that the use of local estrogen may compromise the effects of tamoxifen, but rather the efficacy of vaginal estrogen may be compromised by tamoxifen. turdee DW et al. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010;13:

23 What about aromatase inhibitors? (AI) Aromatase inhibitors can cause severe vaginal atrophy AIs inhibit the activity aromatase by 95% and reduce plasma E2 levels from approximately 20 pmol/l to 3 pmol/l or less. A major issue is whether even minor changes in serum E2 levels from vaginal absorption of topical estrogens might increase breast cancer risk. hort-term follow-up results and no data on breast cancer outcomes are all that is available, yet many patients and physicians are avoiding all estrogen therapy in this setting.

24 Testosterone and breast cancer

25 Testosterone and breast cancer

26 Testosterone and breast cancer Testosterone (T) and related androgens are produced by the ovaries and adrenal glands. They are important intermediate precursors to estrogen in the female body. The concentration of T in women is one-tenth to one-twentieth that of men. Testosterone induces proliferation of the vaginal epithelium T s conversion to estrogen is blocked by AIs, it is hypothesized that topical testosterone would reverse the atrophic changes of estrogen suppression without interfering with the activity of the AI hufelt CL et al. Testosterone and the breast. Menopause Internat 2008;14:

27 Figure 1 chematic representation of the role of ovarian and adrenal sources of sex steroids in premenopausal women. Labrie F Endocr Relat Cancer 2006;13:

28 Testosterone and estrogen

29 Topical testosterone for BC patients with vaginal atrophy In this study, it was sought to determine the impact of 28-day trial of daily vaginal testosterone on estradiol levels and, secondarily, on pathological and clinical measures of vaginal atrophy in women with breast cancer on long-term AI therapy. erum estradiol levels remained low after therapy 18 were undetectable (<5 pg/ml), one was 7 pg/ml, and one was 7.6 pg/ml. There was no significant difference in median serum estradiol level before and after treatment (p =.91) and no difference in post-treatment estradiol levels between dosing levels (p >.99) Witherby et al. Topical testosterone for breast cancer patients with vaginal atrophy related to aromatase inhibitors: a phase I/II study. The Oncologist 2011;16:

30 Witherby et al. Topical testosterone for breast cancer patients with vaginal atrophy related to aromatase inhibitors: a phase I/II study. The Oncologist 2011;16: Topical testosterone for BC patients with vaginal atrophy

31 Topical testosterone for BC patients with vaginal atrophy Twenty-eight days of topical testosterone was associated with improved symptoms of vaginal atrophy in 20 women on AIs without raising estradiol levels. The main limitation of this study is the lack of concurrent controls, which leaves our findings vulnerable to regression to the mean. Longer-term trials are warranted.

32 Testosterone and breast cancer Many of the epidemiological studies that have appropriately controlled for estrogen levels in their models have shown a reduced or no increased breast cancer risk with increasing endogenous concentrations of T. Clinical studies in which women received both estrogens and T are inconclusive with regards to breast cancer risk, and to date, the breast effects of T alone in the postmenopausal woman not receiving HT have not been investigated. The predominant data shows that low dose T use is safe in regards to the breast and endometrium with experimental data suggesting a decrease in estrogen-induced breast epithelial proliferation hufelt CL et al. Testosterone and the breast. Menopause Internat 2008;14:

33 afety of testosterone use in women Data is mixed with outcomes of breast cancer risk, with some experimental studies suggesting a decrease in estrogeninduced breast epithelial proliferation with low dose testosterone. As with all hormone therapy in postmenopausal women, testosterone therapy should be individualized and requires that each woman weigh the risk and benefits. Potential side effects of T therapy include mild and reversible acne and hirsuitism, as well as changes to the lipid profile with oral, but not transdermal T. hufelt CL et al. afety of testosterone use in women. Maturitas 2009;63:63-6.

34 Non-hormonal: moisturizers vs lubricants

35 Vaginal moisturizers Vaginal moisturizers are non-hormonal, over-the-counter products intended to be used several times a week routinely for overall vaginal health and comfort, regardless of sexual activity. Hydration of vaginal mucosa to prevent pain and discomfort Most are gels administered either in a tampon-shaped applicator or as a vaginal suppository. Women are instructed to apply the moisturizer prior to bedtime for the best absorption. Carter J et al. imple strategies for vaginal health promotion in cancer survivors. J ex Med 2011;8:

36 Vaginal moisturizers Replens is a hydrophilic insoluble cross-linked polymer heavily saturated with water, which binds to the vaginal tissue and is eliminated with epithelial cell turnover. The efficacy on vaginal symptoms is lower as compared to ET in all the published trials. Reduction in patient-reported vaginal dryness and discomfort during intercourse seemed to be primarily contained within the first weeks of treatment in both groups. The beneficial effects on symptoms related to vaginal atrophy of this acidic product are likely related also to its buffering properties, which lead to a decrease of vaginal ph.

37 Vaginal lubricants Vaginal lubricants are usually a liquid or gel meant to be applied around the clitoris and labia minora and inside the vaginal entrance to minimize dryness and pain during sexual activity. The lubricant should be applied to both partners genitals prior to vaginal penetration to minimize friction and irritation. Lubricants may need to be reapplied once or several times during sexual activity. ome lubricants are packaged as vaginal suppositories that melt with body heat. It is best to use these at least a few minutes before vaginal penetration to give them time to fully dissolve. Carter J et al. imple strategies for vaginal health promotion in cancer survivors. J ex Med 2011;8:

38 Vaginal lubricants Petroleum-based lubricants are not recommended since they may increase the risk of vaginal infection and also tend to have an unpleasant odor. Petroleum-based lubricants can also damage latex condoms, making them ineffective in preventing pregnancy or protecting against sexually transmitted infections. When used properly, vaginal lubricants can prevent the irritation and mucosal tears that cause postcoital pain and increase the risk of vaginal and urinary tract infections. Carter J et al. imple strategies for vaginal health promotion in cancer survivors. J ex Med 2011;8:

39 Non-pharmacological options Pelvic floor muscle control Vaginal dilator therapy Regular sexual activity Counselling Group support Carter J et al. imple strategies for vaginal health promotion in cancer survivors. J ex Med 2011;8:

40 Barriers to communication with health care providers Despite the rather extraordinary prevalence and diversity of urogenital atrophy-associated symptoms, only about 25% of women suffering from them actually volunteer the information to their health-care professionals. 70% say that their health-care professional only rarely or never asks about problems like vaginal dryness. Physicians rarely bring up the topic of sexual function. Lack of time and resources, limited experience discussing topics, inadequate knowledge, and embarrassment have been cited. turdee DW et al. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010;13:

41 Barriers to communication As opposed to knowledge about hot flushes, women may not be fully aware of the link between vaginal discomfort and declining estrogen levels. ome women erroneously attribute vaginal dryness during the perimenopausal transition to infrequent intercourse, loss of interest or difficulties in the relationship, or just another vagary of aging. It would appear that patients and practitioners alike attribute the symptoms to a natural and unavoidable part of the aging process. turdee DW et al. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010;13:

42 Advice to physicians Reassure your patient that vaginal atrophy is reversible. The old adage of becoming all dried up after menopause indeed still crosses some women s minds. Counsel her that vaginal dryness is not a temporary discomfort similar to hot flushes which usually resolves with time. turdee DW et al. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010;13:

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44 Prospective solutions In spite of recent reassurances to the contrary, many women still fear systemic estrogen therapy. Emphasize the option to treat symptoms vaginally. For a woman with breast cancer, confirm with her oncologist that your recommendations comply with her cancer treatment strategy. Promote discussions about vaginal health promotion by giving a mid-level provider in a site-specific clinic or an oncology practice-specific training on providing basic sexual counseling. Resources, including brochures, books, and videos about vaginal health promotion, cancer and sexuality can be compiled into a patient library, which can provide more detailed information than afforded by brief clinic appointments

45 Conclusions For women with breast cancer, non-hormonal therapies are preferred, but where these are ineffective, vaginal estrogens can be used at the lowest effective dose with appropriate patient counselling. Additional progestogen is not indicated when appropriate lowdose, local estrogen is used, although long-term data (more than 1 year) are lacking. Vaginal health is essential for all women in preventing chronic vulvar irritation, promoting overall comfort, as well as enhancing compliance with gynecologic surveillance.

46 Vaginal estrogens for atrophic vaginitis in BC survivors Dr. John Lamont and Dr. Erin MacLellan, PGY-4 OB/GYN Prospectively assess safety, objective improvement and patient satisfaction in this population with vaginal estrogens Inclusion criteria: at least 1 year post-active treatment with chemo/rads/surgery, at least 1 year post-menopausal Exclusion criteria: use of hormonal therapy in last 3 months, disease recurrence, and undiagnosed vaginal/uterine bleeding

47 Vaginal estrogens for atrophic vaginitis in BC survivors Premarin vaginal cream 1g per vagina 3x/week x 12 weeks, followed by option to switch to Vagifem tablets or Estring Venipuncture at baseline, 2 weeks, 4 weeks, 12 weeks Measure estrone, estradiol, testosterone and HBG Photographs of vaginal tissue and patient satisfaction questionnaire at baseline and 12 weeks

48 Vaginal estrogens for atrophic vaginitis in BC survivors Interested women may contact Dr. Lamont's office for an initial assessment or to discuss the research project further Vaginal estrogens are first-line therapy for atrophic vaginitis Potential to significantly improve QOL for women suffering with this condition Limited studies to support use in breast cancer survivors to this point

49 Contact us Dr. Lamont's office: (905) to ask about vaginal estrogen research project

50 References Melisko ME et al. Amelioration of sexual adverse effects in the early breast cancer patient. J Cancer urviv 2010(4): ayakhot P et al. Potential adverse impact on ovariectomy on physical and psychological function of younger women with breast cancer. Menopause 2011;18(7): Biglia N et al. Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study. Gynecol Endocrinol 2010; 26(6): turdee DW et al. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010;13: Ochsenkuhn R et al. Menopausal status in breast cancer patients with past chemotherapy determines longterm HDD. J exual Med 2011;8: hufelt CL et al. Testosterone and the breast. Menopause Internat 2008;14: hufelt CL et al. afety of testosterone use in women. Maturitas 2009;63:63-6. Carter J et al. imple strategies for vaginal health promotion in cancer survivors. J ex Med 2011;8: Witherby et al. Topical testosterone for breast cancer patients with vaginal atrophy related to aromatase inhibitors: a phase I/II study. The Oncologist 2011;16: