Download Sex after breast cancer: a forgotten burden

Sex after breast
cancer: a forgotten
burden?
Erin MacLellan
PGY-4 Obstetrics and Gynecology
McMaster University
S
Objectives
S Review significance of the problem of vaginal atrophy in
survivors of breast cancer
S Raise topic of hypoactive sexual desire disorder (HSDD)
S Discuss treatment options including pharmacological and
non-pharmacological choices
S Recommend strategies to overcome barriers in dialogue
about sexual dysfunction with health care providers
Overview
S Background
S Female pelvic anatomy
S Estrogen physiology and urogenital atrophy
S Hormonal therapy
S Non-hormonal therapy
S Conclusions
Background
S 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.
S Many breast cancer patients receive multi-modality therapy
including surgery, chemotherapy, and hormonal therapy which
cure disease or prolong life.
S Among breast cancer survivors, vaginal dryness and loss of
libido represent some of the most challenging long term side
effects of breast cancer treatment.
Cycle of pain
Background
S 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.
S This may lead to symptomatic vaginal dryness and irritation as
well as dyspareunia.
S Estrogen deprivation also leads to an elevation in vaginal pH
which may increase the risk of vaginal and urinary tract
infections.
Female pelvic anatomy
Location of estrogen receptors
and the onset of these physical findings is variable. The
oss of rugosity is due to the breakdown of the collagen
support of the vaginal epithelium. Collagen turnover is
ncreased in aging women without hormone therapy,
and these changes may be of importance in vaginal
prolapse3–5.
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
vagina1. Atrophy of the urethra with a relative incr
in urethral epithelial transitional cells, and a co
sponding decrease in intermediate and superfi
Effects of estrogen on vaginal
epithelium
Ovariectomy in younger breast
cancer patients
S 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
S Sexual feelings for partners (P = 0.02) and sexual frequency (P =
0.01) were less in women with ovariectomy compared with women
without ovariectomy.
S Feelings of physical health, attractiveness, overall appearance,
and satisfaction were significantly lower in ovariectomized women
(P < 0.05).
Sayakhot P et al. Potential adverse impact on ovariectomy on
physical and psychological function of younger women with
breast cancer. Menopause 2011;18(7):786-93.
Prevalence of hypoactive
sexual desire disorder (HSDD)
S Most common sexual complaint in women
S Persistently or recurrently deficient sexual fantasies and
desire for sexual activity
S Result in marked distress or interpersonal difficulty
S 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 HSDD. J Sexual Med
2011;8:1486-94.
Prevalence of HSDD
S Examine effect of past chemo and adjuvant endocrine therapy
on sexual desire on young women with breast cancer
S University of Munich
S 34 patients with breast cancer treated with
surgery/chemo/endocrine therapy
S 13 patients with benign breast disease served as controls
S Standardized questionnaire
Ochsenkuhn R et al. Menopausal status in
breast cancer patients with past chemotherapy
determines longterm HSDD. J Sexual Med
2011;8:1486-94.
Prevalence of HSDD – key
results
S 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
S There is a statistically significant association between
menopausal status and mean SIDI-F scores
S 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.
Hormonal options
Hormonal options
Low-dose vaginal estrogens
S Starting hormone therapy necessitates a discussion of
the treatment‘s risks, benefits, and alternatives.
S Cancer survivors, particularly women who have had
breast cancer, are typically reluctant to try hormones
because of their concerns about the potential cancer risk.
S Cancer survivors, particularly women with non-hormone-
dependent cancer, can be appropriate candidates for
vaginal estrogens in combination with non-hormonal
strategies.
Low-dose vaginal estrogens
for urogenital atrophy
S 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.
S Severity of vaginal atrophy was assessed using subjective
[Vaginal Symptoms Score (VSS), Profile of Female Sexual
Function (PFSF)] and objective [Vaginal Health Index (VHI),
Karyopycnotic Index (KI)] evaluations
S Safety 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):404-12.
Low-dose vaginal estrogens
for urogenital atrophy
S Endometrial thickness did not significantly change during
treatment, with a mean increase of 0.5 mm after 3 months of
vaginal ET.
S Did not find any significant modification of hormone serum
values at the end of the treatment period as compared to
baseline.
S 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):404-12.
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 PFSF in patients treated with vaginal estrogen therapy and vaginal moisturizer at the end of the treatment period as
compared to baseline.
PFSF variables
Sexual desire
Sexual arousal
Orgasm
Sexual pleasure
Sexual concerns
Sexual responsiveness
Sexual self-image
Global ‘satisfaction with sexuality’
T ime interval
Vaginal estrogen therapy (%)
p-value
Vaginal moisturizer (%)
p-value
– 12
– 12
– 12
– 12
– 12
– 12
– 12
– 12
" 3.3
0.0
" 4.6
" 6.1
" 2.1
" 6.3
" 11.7
" 60.0
0.41
1.00
0.03
0.001
0.17
0.01
0.05
0.00
# 5.7
0.0
# 5.8
" 3.2
" 5.7
# 4.5
" 33.3
" 33.3
0.22
1.00
0.18
0.18
0.42
0.27
0.47
0.42
Basal
Basal
Basal
Basal
Basal
Basal
Basal
Basal
weeks
weeks
weeks
weeks
weeks
weeks
weeks
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):404-12.
Low-dose vaginal estrogens
for urogenital atrophy
S 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.
S 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):404-12.
Limited data
S Retrospective, case-controlled or cohort studies
S Short follow-up
S Small numbers – 6-75 women using vaginal estrogens
S Population often combined with oral HRT
S Conclusion: ERT does not have a significant adverse
effect on cancer outcome; no increased risk of recurrence
or death
What about tamoxifen use?
S 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.
Sturdee DW et al. Recommendations for the
management of postmenopausal vaginal atrophy.
Climacteric 2010;13:509-22.
What about aromatase
inhibitors? (AI)
S Aromatase inhibitors can cause severe vaginal atrophy
S AIs inhibit the activity aromatase by 95% and reduce plasma
E2 levels from approximately 20 pmol/l to 3 pmol/l or less.
S A major issue is whether even minor changes in serum E2
levels from vaginal absorption of topical estrogens might
increase breast cancer risk.
S Short-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.
Testosterone and breast
cancer
Testosterone and breast
cancer
Testosterone and breast
cancer
S Testosterone (T) and related androgens are produced by the
ovaries and adrenal glands.
S They are important intermediate precursors to estrogen in the
female body.
S The concentration of T in women is one-tenth to one-twentieth that
of men.
S Testosterone induces proliferation of the vaginal epithelium
S 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
Shufelt CL et al. Testosterone and the
breast. Menopause Internat 2008;14:11722.
Figure 1 Schematic representation of the role of ovarian and adrenal sources of sex steroids
in premenopausal women.
Labrie F Endocr Relat Cancer 2006;13:335-355
Testosterone and estrogen
Topical testosterone for BC
patients with vaginal atrophy
S 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.
S Serum 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 S et al. Topical testosterone for breast
cancer patients with vaginal atrophy related to
aromatase inhibitors: a phase I/II study. The
Oncologist 2011;16:424-31.
Topical testosterone for BC
patients with vaginal atrophy
Witherby S et al. Topical testosterone for
breast cancer patients with vaginal
atrophy related to aromatase inhibitors:
a phase I/II study. The Oncologist
2011;16:424-31.
Topical testosterone for BC
patients with vaginal atrophy
S Twenty-eight days of topical testosterone was associated
with improved symptoms of vaginal atrophy in 20 women
on AIs without raising estradiol levels.
S The main limitation of this study is the lack of concurrent
controls, which leaves our findings vulnerable to
regression to the mean.
S Longer-term trials are warranted.
Testosterone and breast
cancer
S 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.
S 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.
S 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
Shufelt CL et al. Testosterone and the
breast. Menopause Internat 2008;14:11722.
Safety of testosterone use in
women
S 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.
S As with all hormone therapy in postmenopausal women,
testosterone therapy should be individualized and requires that
each woman weigh the risk and benefits.
S 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.
Shufelt CL et al. Safety of testosterone
use in women. Maturitas 2009;63:63-6.
Non-hormonal: moisturizers vs
lubricants
Vaginal moisturizers
S 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.
S Hydration of vaginal mucosa to prevent pain and discomfort
S Most are gels administered either in a tampon-shaped
applicator or as a vaginal suppository.
S Women are instructed to apply the moisturizer prior to bedtime
for the best absorption.
Carter J et al. Simple strategies for
vaginal health promotion in cancer
survivors. J Sex Med 2011;8:549-559.
Vaginal moisturizers
S 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.
S The efficacy on vaginal symptoms is lower as compared to ET in all the
published trials.
S Reduction in patient-reported vaginal dryness and discomfort during
intercourse seemed to be primarily contained within the first weeks of
treatment in both groups.
S 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.
Vaginal lubricants
S 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.
S The lubricant should be applied to both partners‘ genitals prior to
vaginal penetration to minimize friction and irritation.
S Lubricants may need to be reapplied once or several times during
sexual activity.
S Some 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. Simple strategies for
vaginal health promotion in cancer
survivors. J Sex Med 2011;8:549-559.
Vaginal lubricants
S Petroleum-based lubricants are not recommended since they
may increase the risk of vaginal infection and also tend to have
an unpleasant odor.
S Petroleum-based lubricants can also damage latex condoms,
making them ineffective in preventing pregnancy or protecting
against sexually transmitted infections.
S 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. Simple strategies for
vaginal health promotion in cancer
survivors. J Sex Med 2011;8:549-559.
Non-pharmacological options
S Pelvic floor muscle control
S Vaginal dilator therapy
S Regular sexual activity
S Counselling
S Group support
Carter J et al. Simple strategies for vaginal health
promotion in cancer survivors. J Sex Med 2011;8:549559.
Barriers to communication with
health care providers
S 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.
S 70% say that their health-care professional only rarely or never
asks about problems like vaginal dryness.
S Physicians rarely bring up the topic of sexual function.
S Lack of time and resources, limited experience discussing
topics, inadequate knowledge, and embarrassment have been
cited.
Sturdee DW et al. Recommendations for the
management of postmenopausal vaginal atrophy.
Climacteric 2010;13:509-22.
Barriers to communication
S As opposed to knowledge about hot flushes, women may not
be fully aware of the link between vaginal discomfort and
declining estrogen levels.
S Some 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.
S It would appear that patients and practitioners alike attribute the
symptoms to a natural and unavoidable part of the aging
process.
Sturdee DW et al. Recommendations for
the management of postmenopausal
vaginal atrophy. Climacteric
2010;13:509-22.
Advice to physicians
S
Reassure your patient that
vaginal atrophy is reversible.
S
The old adage of becoming ‗all
dried up‘ after menopause
indeed still crosses some
women‘s minds.
S
Counsel her that vaginal
dryness is not a temporary
discomfort similar to hot flushes
which usually resolves with
time.
Sturdee DW et al. Recommendations for
the management of postmenopausal
vaginal atrophy. Climacteric
2010;13:509-22.
Prospective solutions
S
In spite of recent reassurances to the contrary, many women still fear systemic
estrogen therapy.
S
Emphasize the option to treat symptoms vaginally.
S
For a woman with breast cancer, confirm with her oncologist that your
recommendations comply with her cancer treatment strategy.
S
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.
S
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
Conclusions
S 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.
S Additional progestogen is not indicated when appropriate low-
dose, local estrogen is used, although long-term data (more
than 1 year) are lacking.
S Vaginal health is essential for all women in preventing chronic
vulvar irritation, promoting overall comfort, as well as
enhancing compliance with gynecologic surveillance.
Vaginal estrogens for atrophic
vaginitis in BC survivors
S Dr. John Lamont and Dr. Erin MacLellan, PGY-4 OB/GYN
S Prospectively assess safety, objective improvement and patient
satisfaction in this population with vaginal estrogens
S Inclusion criteria: at least 1 year post-active treatment with
chemo/rads/surgery, at least 1 year post-menopausal
S Exclusion criteria: use of hormonal therapy in last 3 months,
disease recurrence, and undiagnosed vaginal/uterine bleeding
Vaginal estrogens for atrophic
vaginitis in BC survivors
S Premarin vaginal cream 1g per vagina 3x/week x 12
weeks, followed by option to switch to Vagifem tablets or
Estring
S Venipuncture at baseline, 2 weeks, 4 weeks, 12 weeks
S Measure estrone, estradiol, testosterone and SHBG
S Photographs of vaginal tissue and patient satisfaction
questionnaire at baseline and 12 weeks
Vaginal estrogens for atrophic
vaginitis in BC survivors
S Interested women may contact Dr. Lamont's office for an
initial assessment or to discuss the research project
further
S Vaginal estrogens are first-line therapy for atrophic
vaginitis
S Potential to significantly improve QOL for women
suffering with this condition
S Limited studies to support use in breast cancer survivors
to this point
Contact us
S Dr. Lamont's office: (905) 574-
8606 to ask about vaginal estrogen
research project
References
S
Melisko ME et al. Amelioration of sexual adverse effects in the early breast cancer patient. J Cancer Surviv 2010(4):247-55.
S
Sayakhot P et al. Potential adverse impact on ovariectomy on physical and psychological function of younger women with breast cancer.
Menopause 2011;18(7):786-93.
S
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):404-12.
S
Sturdee DW et al. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010;13:509-22.
S
Ochsenkuhn R et al. Menopausal status in breast cancer patients with past chemotherapy determines longterm HSDD. J Sexual Med
2011;8:1486-94.
S
Shufelt CL et al. Testosterone and the breast. Menopause Internat 2008;14:117-22.
S
Shufelt CL et al. Safety of testosterone use in women. Maturitas 2009;63:63-6.
S
Carter J et al. Simple strategies for vaginal health promotion in cancer survivors. J Sex Med 2011;8:549-559.
S
Witherby S et al. Topical testosterone for breast cancer patients with vaginal atrophy related to aromatase inhibitors: a phase I/II study.
The Oncologist 2011;16:424-31.