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Sexual dysfunction in women

with cancer
,.b .d
Sandy J. Falk, M.D. and Don S. Dizon, M.D.
a Sexual Health Program, Dana Farber Cancer Intitute!
b
De"artment o# $btetric, %ynecology, and &e"roducti'e
Medicine, Har'ard Medical School, Har'ard (ni'erity,
c
De"artment o# Internal Medicine, Har'ard Medical School,
Har'ard (ni'erity, and
d
$ncology Sexual Health, Maachuett %eneral Ho"ital Cancer Center, )oton, Maachuett
*""roximatel
y
+, million "eo"le ha'e a hitory o# cancer in the (nited State alone, and the number i ex"ected to increae -ith time.
.hi ha "rom"ted an a""reciation o# the /uality o# li#e
for
ur'i'or. 0omen treated #or cancer identi#y gynecologic iu
e
a a ma1or
concern for both general health and the negati'e im"act on exual #unction that #ollo- the cancer diagnoi and ube/uent
treatment. Unfortunately, issues related to sexual health continue to be undera""reciated. *lthough com"reheni'e
cancer center ha2e ado"ted specialized centers for survivorship issues, including thoe in'ol'ing exual health,
conultation are not -idely a'ailable in mot
communities. We provide background information on treatment exual health,
examine the im"act
women who have received a cancer diagnosis and been ube/uently treated.
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Medicine.5
Discuss: 6ou can dicu thi article -ith it author and -ith other *S&M member at htt"788
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c%m8#alk2exual2dy2sfune*om'canmd'2 22
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With ad'ance in early detec2 t i o n
a n d t r e a t me n t # o r c a n c e r , t h e
n u mb e r o # u r ' i ' o r rnntinues
to increase' and accordingly there
has been an increased awareness of
survivorship issues. It i
etimated t hat a o# January 9:+9
t here -ere +;.< million "eo"le -ith a
hitory o# cancer in the (nited
State, and the number i ex"ected to
increae to += million by 9:99 3+5. For
#emale cancer ur'i'or, gynecologic
iue are a ma1 or concern, and
many o# t hee iue im"act exual
#unction. Some tertiary care center
ha'e de'elo"ed exual health
"rogram "eci#icall y #or thi "atient
"o"ulation, but ex"ert conultation are
not -idely a'ailable. In addition, mot
oncologit are unable or un-illing to
dicu exuality and i nt i macy i n
t he cont ext o# a #ollo-2u" oncology
'iit becaue o# their lack o# training in
thi area, "er
onal dicom#ort, or time contraint.
Int ead, t hee i ue are rarel y ad2
dreed, and -hen "atient ak about
exual dy#unction, it i generally to
the primary care physician or gyneco-
logist, -ho may be un#amiliar -i th
thee iue a they "ertain to -omen
"re'iouly treated
-
#or cancer. In thi
article, -e -ill re'ie- exual health
iue in -omen -ho ha'e had a cancer
diagnoi and ube/uent treatment,
and -e -ill #ocu in greater de"th on
dy"areunia and 'aginal tenoi, t-o o#
t he mot common or i gni #i cant
clinical cenario.
OVERVIEW OF SEXUAL
DYSFUNCTION IN WOMEN
TREATED FOR CANCER
Sexual health condition that a##ect
-omen during or a#ter cancer treatment may
be considered according to the
ame cat egori e a #emal e exual
dy#unction in the general "o"ulation.
.he *merican Pychiatric *ociation
de#ine the #ollo-ing #emale exual
di order7 exual i nt eret 8 aroual ,
orgamic, and genito"el'ic "ain8"ene2
tration 395. Cancer and it treatment
can directly caue all o# thee condition.
Surgical treatment can reult in
ditortion o# #emale anatomy, "articu2
larly #or "atient -ith breat or gyneco2
logic cancer. In addition, the remo'al
o# t he o'ar i e i n "r emeno"au al
-omen lead to "remature meno"aue
-ith reultant hormonal and "hyical
change that can alter e'eral domain
o# exual #unction. Surgical treatment
can reult in exual dy#unction #or
-omen diagnoed -ith other tumor
a -ell! a an exam"le, exual dy#unc2
t i on i occur i n +=> and ?@> o#
-omen treated #or earl y tage rectal
cancer 3;5.
Chemotherapy can result in sys-
temic efects that dampen both sexual
desire and arousal. In addition, chemo-
therapy may induce ovarian failure
afect a "atien
t
el#2"erce"tion o# exual attracti'ene, and
oue treatment may caue 'aginal or rectal mucoal toxicity
3,5. For "atient treated -ith high2doe chemothera"y a "art o#
a tem cell tran"lantation "rotocol, the additional toxicity may
induce 'ul'o'aginal gra#t2versus-host disease 3%AHD5. Be i
kno-n about the effects of chemotherapy on the #emale
genital tract other than, the ovaries, although women may
ex"erience a persistent vaginal discharge after chemothera"y,
-hich likely re"reent 'aginal mucoiti! alo, there i ome
e'idence that chemothera"y contribute to 'ul'odynia 3?5. In
addition, the ex"erience o# cancer diagnosis and treatment may
profoundly afect a woman's body image and sense of
sexuality (6).
Radiation therapy (RT) can also impact sexual #unction in
-omen. For exam"le. &. #or breat cancer induce local kin
i&ening, conuacture, andior change in texture and color.
a" may result m chronic breast pain, an) of which can a##ect a
v s body unage or ability to enjoy sexual activity.
V!" fdtas# away result from $% to the pelvis with
re&ailaat vaginal fibrosisor stenosis that limits a woman's
capacity for vaginal intercourse as well as affects her genital
pelvic and clitoral sensitivity during sexual acti'ity. .hee
changes last long after $% has been com"leted. For exam"le,
-omen treated #or cer'ical cancer ha'e re"orted exual
dy#unction u" to ? year later 3<5.
ADDRESSING SEXUAL HEALTH IN CANCER
SURVIVORS
.he general a""roach to exual health iue aociated -ith
cancer treatment. like many condition, in'ol'e "atient
edmcafio(# screening, diagmmis. and management %oo often,
=W ad aae
)

*
are %he only goat of the oncolog+ and, in
the context of a busy practice, survivorship iue including
exual health are relegated to other "ro'ider uch a ocial
-orker or "rimary care "ro'ider. 0ithout an ex"licit under2
tanding o# ho- the care o# the cancer ur'i'or i coordinated,
iue uch a exualit y are o#ten le#t unattended. * an
exam"le, 0iggin et al. 3=5 conducted a ur'ey o# gynecologic
oncologit and #ound that le than hal# made it a "ractice to
take a exual hitory in ne- "atient and =:> did not #eel
there -a u##icient time to de'ote to ex"loring exual iue.
$nly 9:> #elt they had u##icient time to "eak to their
"atient about thee iue, -hich -a the entiment o# both
male 3=?>5 and #emale 3<;>5 re"ondent.
Approaching Patients beore Treat!ent
Ideally, antici"atory guidance regarding exual health iue
hould be a key element o# "atient education be#ore treatment
#or cancer, but many -omen -ho ex"erience exual ad'ere effects
complain that they were not informed
in
advance. %he typical
se,uence ofcvvnb that accompanies ancer diagnosis and
treatment re,uires the complete attention o# the "atient and
her medical team, and thi o#ten doe not allo- #or
"roacti'ely addreing "ottreatment /uality o# li#e iue.
.here#ore, the a""ro"riate timing o# thi dicuion cannot
"erti#it$ an% Steri#it$&
' $ne a""roach that ha -orked for
"
ine oncology darts
i to re'ie- the ty"ical coure o# "atient care and counseling
for a particular tumor ite. .he team can ther, identi#ythe
mot a""ro"riate time to counel "atient about the "otential
#or exual health iue.
Approaching Patients ater Treat!ent
$nce acti'e cancer treatment ha been com"leted, "atient
hould be creened #or exual health iue. Sexual health
concern are common among thoe com"leting treatment
and -hile mot com"laint can be treated, o""ortunitie to
addre them are o#ten mi ed. In one t udy o# "at ient
follow-up observation after pelvic radiation, exual iue
were addressed in only 9?> o# 'iit 3@5.
)arrier t o addressing sexual healt h iue exi t ,
including time contraint or a reluctance to e'en
bring u" exual health iue on the "art o# clinician,
and the ene that many -omen #eel embarraed to ak
about thee iue or may be una-are that treatment i a'ailable
3+:5. In addition, ome "atient may be concerned that their
oncologit -ill "ercei'e that thee iue are tri'ial or that
the "atient i ungrate#ul #or their care. Ho-e'er, /uerie
about exual health can be made 2in a -ay that i2
com#ortableC #or "at i ent , and /uet i on can be
i ncor"orat ed i nt o a routine "ottreat ment re'ie- o#
ytem. In addition to aking thee /uetion, it i
im"ortant to enure that reource are a'ailable locally #or
"atient -ho -ih to "urue #urther treatment.
0hen addreing exual #unction, it i eential that
aum"tion not be made regarding exual orientation or ex2
ual "ractice 3++5. .he "atient hould be aked o"en2ended
,uestions that allow her to feel com#ortable haring in#orma2
tion that is pertinent to her e'aluation and management. For
exam"le, 'aginal intercoure may not be the mot im"ortant
com"onent o# exual acti'ity #or many -omen, including
thoe -ho ha'e ex -ith other -omen.
DIAGNOSIS
.he diagnoi o# exual health iue re/uire a hitory o# the
exual com"laint and a "ertinent medical hitory, including
an oncologic and exual hitory. * medication hitory hould
alo be re'ie-ed becaue o# their im"act on exual #unction,
including the ue o# antide"reant and endocrine thera"ie.
It i im"ortant to ae the a"ect o# exual dy#unction that
are botherome to the "atient, including -hether concomitant
ym"tom o# anxiety or de"reion are "reent 3+9, +;5.
Detailed diagnoi and treatment o# exual deire, aroual,
and orgam iue i beyond the co"e o# thi article, but
many re'ie- o# thee to"ic can be #ound in the literature
3+,2+D5. E'aluat ion and t reat ment o# t hee i ue may
necessitate referral to a behavioral health "ecialit or sex
therapist.
It i im"ortant to dicu the interaction bet-een the
"atient and exual "artner, both exually and in term o#
the relationhi" in general. it may alo be hel"#ul to dicu
) 13 1 VOL. 100 NO. 4 / OCTOBER 2013
1 917
VIEWS AND REVIEWS
.he e'aluation hould include a "el'ic, examination, in
-hich the 'ul'a and 'agina are examined #or the "reence
and e'eri t y o# at ro"hy, change i n 'agi nal l engt h or
caliber due to urgery or "el'
i
c radiation, or adheion.
Care houl d be t aken t o communi cat e -i t h t he "at ient
regarding her ability to tolerate the examination! di##iculty
may be ym"tomatic o# dy"areunia. For thee -omen, the
ue o# a narro- Pederon or "ediatric "eculum may be
better tolerated. (e o# a lubricating gel increae com#ort
and generall y doe not i nt er#ere -i th cer'i cal am"l e
3+<, +=5.
TREAT(ENT
Treatment
must
be individualized
in
kee"ing -ith the
patient's goals. Although the o'erall goal o# management i
to enable -omen to be com#ortable -ith their ex li#e, the
ob1ecti'e may di##er tc, include achie'ement o#
orgam, decreaed "ain -ith "enetration, orim"ro'ed exual
deire. Such goal may di##er bet-een the "atient and her
"artner, -hich may re/uire re#erral #or cou"le thera"y or
ex thera"y. In addition, not all -omen ha'e a current exual
"artner, and thee "atient may re/uet an e'aluation to
enure their exual health #or the #uture.
Dyspareunia
D
y
"areunia i the mot common exual com"laint among
female cancer ur'i'or. .he mot common caue o#
dyspareunia in this population is vulvovaginal atrophy
resulting from bypoestrogenism (19). This may be due to
menopause induced by urgery, chemothera"y, or "el'ic
radiation or may be caued by endocrine thera"y, mainly
#or breat cancer 3e.g., aromatae inhibitor, tamoxi#en5.
Aul'o'aginal atro"hy i characterized by dryne, thinning
o# the e"it heli al l ining, and i n#lammat ion. .hi lo o#
lubrication and elaticit y along -ith the thinning o#
the epithelium leads to an increase in discomfort or pain
either on a daily basis or during vulvovagmal contact.
Women with atrophy often develop small lacerations with
sexual contact, particularly at the vaginal fourchette where
the labia majors converge. This often results in postcoital
bleeding, which is self-limited but may result in anxiety
about sexual
Wfvity
2
Dyspanvnia is also an important quality of life issue. This '.
as demonstrated most notably among breast cancer
survivors (A* In one study, dyspareunia was reported by
563% of women taking aromatase inhibitors and 31.3% of
dxxw UWmg tamoxifen (21).
The frst-line treatment for vaginal atro"hy i the
nonhormonal a""roach o# uing 'aginal moiturizer and
lubricant. Moiturizer hould be ued regularly e'eral
time a -eek to ameliorate daily 'aginal dryne. Bubricant
a
r
e intended #or ue during exual acti'ity. .hee "roduct are
a'ailable o'er the counter, and there are many di##erent
brand. 0omen uually try e'eral "roduct to #ind the one
they prefer. In general, water- or ilicone2baed "roduct
rizer i com"arable to 'aginal etrogen thcro"l', but n.2.2any
-omen #ind 'aginal moiturizer and lubrican2.

inu##icient,
in -hich cae greater im"ro'ement can ty"icall
y
be achie'ed
-ith 'aginal etrogen thera"y 39;, 9,5.
Aaginal etrogen thera"y i more e##ecti'e #or treating
'ul'o'aginal atro"hy than ytemic etrogen thera"y 39?5.
Aagi nal et r ogen t her a"y i e##ect i 'e i n t reat i ng t he
ym"tom o# 'ul'o'aginal atro"hy in =:
:
+: to @:> o# -omen
and can be adminitered a an etradiol tablet 3Aagi#em! Fo'o
Fordik FemCare *%5 or a lo-2doe ring uch a Etring
3P#izer5 or Femring 30arner Chilcott, a 'aginal ring that
deli'er a ytemic doe o# etrogen5, or an etradiol cream
3Etrace! 0arner Chilcott5 or con1ugated etrogen cream
3Premarin! P#izer5 3;, 9D5. Bo-2doe 'aginal etrogen thera"y
reult in ome ytemic abor"tion, the le'el de"ending on
the doe and the condition o# the 'aginal e"ithelium! the
degree o# abor"tion a""ear to decreae a the e"ithelium
comitie in re"one to etrogen timulation. For the etradiol
tablet 3Aagi#em, +: ug t-ice -eekl y5 and lo-2doe ring
3Etring, <.? *g daily #or @: day5, a teady2tage erum etra2
in -omen a#ter natural meno"aue 3a""roximately ? "g8mB5
39<, 9=5. .he doe i more di##icult to control in etrogen222
cream becaue o# uer 'ariability, and the erum etrogen
doe i di##icult to meaure in -omen uing con1ugated
e/uine etrogen cream becaue it contain more than 9::
com"ound.
.he ue o# 'aginal etrogen thera"y in -omen -ith etrogen2
eniti'e cancer i a ub1ect o# debate. .hi i
"articularly an iue in -omen -ith breat cancer, although
it may alo be an iue o# concern in -omen -ith ad'anced
endomet ri al cancer or other hormone rece"t or2"oi ti 'e
mal i gnanci e 39@2;+5. .he ue o# 'agi nal et rogen i n
-omen -ith etrogen2rece"tor2"oiti'e breat cancer ha
not been -ell tudied. Fo increae in the rik o# recurrence
-a #ound in a "ro"ecti'e cohort tudy o# -omen -i th
breast cancer that included D@ -omen treated -ith 'aginal
etrogen #or an a'erage o# + year 3range7 :. +2?.: year5
3;95. * concern ha been raied that 'aginal etrogen may
inter#ere -ith the e##icacy o# aromatae inhibitor thera"y.
.-o tudie o# 10 or #e-er -omen ha'e #ound that ue o#
'aginal etrogen thera"y in -omen on aromatae inhibitor
i ncreae erum et radi ol and de"ree gonadot ro"i n
levels (33, 34). * "ro"ecti'e tudy o# D: "atient on
aromatae inhibitor treated -ith 'aginal etradiol tablet i
ongoing 3;?5.
Mot "hyi ci an ue an i ndi 'i dual i zed a""roach t o
'agi nal et rogen u""l ement at i on i n cancer ur'i 'or,
con i t ent -i t h t he "oi t i on o# t he For t h *mer i can
Meno"aue Societ yGnamel y, t hat ome -omen i n t hi
"o"ulation -ith ym"tomatic 'aginal atro"hy unre"oni'e
to nonhormonal thera"ie may -ant to dicu the rik and
bene#it2, o# thi thera"y, but other may -ih to a'oid any
thera"y aociated -ith "otential rik 3;D5.
For -omen -ho decline 'aginal etrogen thera"y and
#or -hom 'aginal moiturizer and lubricant are inu##i 2
cient, ome additional relie# may be obtained -ith the ue
918 1 VOL. 100 NO. 4 / OCTOBER 2013
any
hilpf"
thera
el#2+
ohy
'agir
hoo
gene
men3
ecol
enco,
Vagi
Aagii
-omH
allog
Aagii
"eter
F
maliF
22canct2
may
"oi
radia
and 2
'agir
cell5
toxic
the
conci
'agir
radia
+.9>
.
i not
ym"
attery
obtn
'agir
and tI
i an
#urthi
regar,
'ide i
late
dilate
not
cone3
genit!
dilate
be a
ameliorates d
y
spareunia. Di
l
ators may also be used to
impr
ove
"el'ic mucle relaxation and control as part of
therapy for vaginismus. Patients may be instructed on self-
guided use of dilators or may be referred to a pelvic
self-guided -
physical therapist.
Women with severe pain. particularly localized to the
vaginal vestibule, or pain that is not consistent with atrophy
should be evaluated for vulvodynia. Localized, provoked, or
generalized vulvodynia may develop after chemotherapy or
menopause (5, 37). In addition, some women develop
secondary vaginismus after experiencing painful sexual
encounters.
Vaginal Stenosis
Vaginal tenoi i a
severe
com"lication that occur in ome
women -ho are treated with pelvic radiation thera"y or
.ogninc hematopowtic stem cell transplantation 3JC<+5.
Vaginal obstruction precluding 'aginal intercoure i a
poterifudly devastating outcome.
/elvic $% is used most commonly to treat gynecologic
malignancie 23endometrial, cer'ical, 'aginal, 2 and 'ui'ar
cancer5 and ankI 2andsoldrectal 2 ca=rs 69diation 2
therapy may reult in radiation 'aginiti or 'aginal
#ibroi, with possible vaginal shortening or tenoi. .he
de'elo"ment of radiation fbrosis is a result of damage to the
vaginal mucosa and associated blood vessels and connective
tissues (38). The vaginal tissue eventually
reepithelializes, with excess collagen content and smooth
muscle fbrosis. The degree of toxicit
y
depends on the
dosage, the type of radiation, and li0e schedule a %eU a
#actor uch a "re'iou urgery .
. dwn&&m", and the pri or condi ti onof the
vagina. %he incidence of
vagi nal
obstruction a#ter "el'ic
radiation i uncertain! the re"orted rate range -idely #rom
+.9> to ==> 3;@, ,:5.
.he natural hitory o# 'aginal tenoi aociated -ith &. i
not -ell documented. .he "roce itel# doe not "roduce
ym"tom, and the condition may be brought to medical
attention -hen the -oman or her exual "artner note the
obtruction or it i #ound incidentally on examination. .he
'aginal tiue ty"ically de'elo" a -hitened a""earance,
and the 'agina loe it "liability. It i uncertain -hether there
i an early tage during -hich an inter'ention could "re'ent
#urther 'aginal obtruction.
Mot r adi at i on oncol ogy t eam counel "at i ent
regarding the rik o# 'aginal #ibroi a#ter "el'ic &. and "ro2
'ide intruction in the ue o# a 'aginal dilator. Fibroi i a
late e##ect o# &., and there i o#ten "oor com"liance -ith
dilator thera"y. .he e##icacy o# 'aginal dilator thera"y ha
not been "ro'en, and ome i n'et i gat or ha'e rai ed
Fertility and Sterility
from vaginal dilator therapy, and patients often beneft
from being referred to a pelvic physical therapist. Women
with severe obstruction, who have less than 5 to 6 cm of
residual vaginal length, may require counseling about
modifying their sexual activity to include incomplete vaginal
penetration or other sexual activities.
Pelvic RT also induces ovarian failure in women. Vaginal
estrogen therapy may help ameliorate dyspareunia in these
patients and improve vaginal elast
i
city. Some questions
have been raised regarding whether vaginal estrogen
receptors maintain their function following RT, but studies
have shown that local estrogen therapy increases the vaginal
maturation index in women who have been treated with
pelvic RT (41).
Women who undergo allogeneic IICT may develop
vaginal %AHD. The reported incidence of vulvovaginal
%AHD i 3% of bone marrow reci
p
ients and 15% of peripheral
blood reci"ient, but this condition often goe undetected
becaue ome cae are aym"tomatic and "atient and clinical
a-arene are limited 3,95. 2 Partial or complete vaginal
obtruction occur in a minority of patients, but the actual
incidence is unknown (43).
Aul 'o'aginal %AHD houl d be
-
suspected in any
allogeneic HC. ur'i'or -ho "reent -ith dy"areunia
or a enat i on o# 'agi nal obt ruct i on by t he "at i ent or
her exual "artner. Mild 'ul'o'aginal %AHD i di##icult
to di ##erent iate #rom hy"oetrogenic atro"hy, -hi ch i
o#ten reaonable to treat initially -ith a coure o# 'aginal
etrogen. 0omen -ho do not re"ond to thi thera"y likely
ha'e %AHD, "articularly i# the ym"tom corre"ond -ith
the onet or exacerbation o# %AHD at other ite 3e. g.,
cutaneous or oral). %he diagnoi i o#ten made clinically,
but a biopsy may be "er#ormed. $n examination,
erythematou area or ulceration or laceration may be
"reent, "articularl y in the area o# the 'aginal
#ourchette or the labia minor. Aaginal adheion may be
een, ty"ically in the u""er 'agina. $btructi on may
take the #orm o# an annular ring, ometime -ith an
a"erture through -hich a -ab can be "aed. .he
obtruction and the occluded "roximal area o# the
'agina can be 'iualized on "el'ic ultraound.
.here i no tandard a""roach to treating 'ul'o'aginal
%AHD. Mot "hyician treat initially -ith a to"ical teroid.
I# thi i not e##ecti'e, ue o# to"ical cyclo"orine ha been
re"orted 3,,5! 'aginal tacrolimu ha been tolerated in -omen
treated #or lichen "lanu, but ha not been tudied in %AHD
3,?5. 0omen -i th 'aginal adhei on may bene#it #rom
vaginal dilator therapy or surgery.
CONCLUSION
.he number o# cancer ur'i'or i increaing -orld-ide,
and a uch it i im"ortant to addre iue in
ur'i'orhi". For many -omen, exual health iue are
ting
'25).
the
men
ova
ring
that
,am
9am
"y
on
the
inn
did
tra-
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gen
gen
ited
2-00
iith ;
i
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--ed
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ib
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,ith
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hi
nd
fi-
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e
)13 1 VOL. 100 NO. 4 / OCTOBER 2013
V I EWS A ND RE VI EWS
on sexual pain and vaginal obstruction, but issues of sex-
ual desire, arousal, and orgasm are equally important and
distressing for patient. The presence of a specialized team
to address sexual issues is a valuable resource, but these is-
sues can also be addressed in a coordinated fashion with
oncologists, gynecologists, and primary care physicians
all collaborating in the detection, diagnosis, and treatment
of such concerns.
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VOL.
9" 1 VOL. 100 NO. 4 / OCTOBER 2013