Menopausal Health
Diagnosis and Treatment of the
Non–Sex-related Symptoms
of Vulvovaginal Atrophy
Mary Jane Minkin, MD; Marsha K. Guess, MD
Vulvovaginal atrophy
is a common, chronic
disorder that affects many
postmenopausal women.
Bothersome symptoms,
including dryness, itching,
irritation, incontinence,
and recurrent UTIs, can
be safely and effectively
managed with the
use of local vaginal
estrogen therapy.
D
eclining estrogen levels at
menopause may result in
symptomatic vulvovaginal
atrophy. Up to 45% of postmenopausal women may be
affected, but only about one-fourth of
symptomatic women seek medical help.1,2
Many women are too embarrassed to report their vulvovaginal symptoms and
are unaware that effective, well-tolerated treatments for menopause-related
vulvovaginal discomfort are available.1
The term vulvovaginal atrophy, by definition, encompasses the entire vulvar
Follow OBG Management on
and
region, while the term vaginal atrophy is
more specific. Both are used frequently
in the literature, as are the closely related terms urogenital atrophy and genitourinary atrophy. While all of these terms
may be used, this article will refer to the
condition discussed herein as vulvovaginal atrophy and aims to review the nonsexual, “bothersome” signs and sympDr Minkin is Clinical Professor in the Department of
Obstetrics, Gynecology and Reproductive Sciences
and Dr Guess is Assistant Professor in the Section of
Urogynecology and Reconstructive Pelvic Surgery at Yale
University School of Medicine, New Haven, CT.
The Female Patient | Vol 37 november/december 2012 33
Non-Sex-related Symptoms of Vulvovaginal Atrophy
toms of vulvovaginal atrophy and the
role of clinicians, particularly ObGyns,
in identifying and treating patients with
these symptoms.
Signs and Symptoms of
Vulvovaginal Atrophy
Genital Signs and Symptoms
The diagnosis of vulvovaginal atrophy
is typically based on patient-reported
symptoms and the results of a physical
exam (Tables 1 and 2).3, 4 Vaginal pH and
vaginal maturation index may aid in
confirming the diagnosis. A vaginal pH
test, administered by placing pH paper
against the inside wall of the vagina,
would reveal a pH of 4.6 or above (nor-
Vulvovaginal and Urinary Symptoms
of Vulvovaginal Atrophy
Table 1.
Vulvovaginal
Urinary
• Irritation
• Itching
• Burning
• Dryness
• Dyspareunia
• Light bleeding after intercourse
• Abnormal discharge
• Increased frequency
• Nocturia
• Urgency
• Incontinence
• Dysuria
• Recurrent urinary tract infections
Data from Mac Bride3 and the North American Menopause Society.4
Table 2.
mal premenopausal range: 3.5-4.5) in
the absence of bacterial vaginosis.3 The
vaginal maturation index describes the
relative proportions of superficial, intermediate, and parabasal cells in a smear
taken from the upper third of the lateral
wall of the vagina. A normal, premenopausal smear contains at least 15% superficial cells, while a postmenopausal
smear from a patient with vulvovaginal
atrophy typically contains fewer than
5% superficial cells.3
Urinary Signs and Symptoms
As estrogen receptors are also present in
the lower urinary tract, urinary symptoms, including symptoms suggestive
of overactive bladder (eg, urgency, frequency, and nocturia), are frequently associated with vulvovaginal atrophy (see
Table 1). Diminished estrogen causes the
urethral mucosa and trigone of the bladder to thin and the supporting tissues
and ligaments to weaken.5 A urethral
caruncle, a benign, fleshy outgrowth
at the urethral meatus, may be evident
upon examination.3 Inflammation of the
urethral and vulvar tissues may result
in dysuria, and urinary incontinence
may exacerbate irritation.
Additionally, estrogen deprivation
and increased vaginal pH may promote recurrent urinary tract infections
(UTIs).6 Prior to menopause, estrogen
Signs of Vulvovaginal Atrophy
General
External
Internal
Pale, dry, shiny appearance
Thinning of the vulvar skin
Thinning of vaginal epithelium
Petechiae
Loss of fat pads of mons pubis
and labia majora
Narrowing and shortening of the vagina
Ulcerations
Diminished elasticity and turgor
of tissue
Friability of tissue
Receded labia minora, possibly
with fusion
Receded prepuce
Urethral caruncle
Diminished rugae
Reduced secretions
Erythema indicative of inflammation
(ie, atrophic vaginitis)
Sparse pubic hair
Data from Mac Bride3 and the North American Menopause Society.4
34
The Female Patient | Vol 37 november/december 2012 All articles are available online at www.femalepatient.com
Minkin and Guess
stimulates vaginal epithelial cells to
produce large amounts of glycogen. The
epithelium is thick and sheds regularly
into the vaginal lumen, where the glycogen is released, hydrolyzed to glucose,
and metabolized to lactic acid by native
lactobacilli. At menopause, decreased
estrogen levels reduce the activity of
this pathway. Less lactic acid leads to
increased pH, loss of lactobacilli, and
overgrowth of other species, which may
predispose a patient to symptomatic
vaginal infections or recurrent UTIs.3
Differential Diagnosis
Alternative diagnoses of vulvovaginal
atrophy may include infections (eg, Candida vulvovaginitis, bacterial vaginosis, and trichomoniasis), vulvovaginal
dermatoses (eg, lichen sclerosis, lichen
planus, and lichen simplex chronicus),
contact irritation or allergy, cancerous
or precancerous lesions, and desquamative inflammatory vaginitis.3, 7
Current Recommendations for the
Treatment of Vulvovaginal Atrophy
For initial treatment of vulvovaginal
atrophy symptoms, the North American Menopause Society (NAMS) recommends nonhormonal vaginal lubricants
and moisturizers, as well as continued
intercourse to help promote blood flow
to the area.4 One commonly used moisturizer, Replens (Lil’ Drug Store Products, Inc, Cedar Rapids, IA), has been
shown to decrease or eliminate itching
and irritation when applied three times
per week.8 NAMS has not issued a statement on the use of alternative therapies,
such as phytoestrogens and vitamins.
While these nonprescription treatments can provide some relief of symptoms, they do not affect postmenopausal
estrogen levels, which are the underlying
cause of vulvovaginal atrophy. If nonhormonal interventions have been ineffective or when symptoms of atrophy are
severe, NAMS suggests that estrogen be
considered as a first-line therapy.4, 9 The
American College of Obstetricians and
Gynecologists and the Society of Obste-
tricians and Gynaecologists of Canada
concur with this recommendation.
Systemic estrogen is also considered
effective for the treatment of dryness,
itching, and irritation associated with
vulvovaginal atrophy, although it is not
FoCUSPOINT
If nonhormonal interventions have been
ineffective or when symptoms of atrophy
are severe, NAMS suggests that estrogen
be considered as a first-line therapy.
recommended unless the patient is significantly affected by other menopausal
symptoms, such as hot flashes and night
sweats.9 Over 25% of patients taking
systemic estrogen may still experience
bothersome vulvovaginal symptoms,10
which may be improved by local vaginal estrogen. Systemic estrogen has no
proven benefit for UTI,6 incontinence,11
or overactive bladder symptoms.12
Local Vaginal Estrogen
Treatment Options for Local Vaginal
Estrogen
All available local vaginal estrogen
products approved for use in the United
States (Estrace, Estring, Premarin, Vagifem; see Table 313-16) are considered effective and well tolerated at their recommended dosage.4 However, patients may
wish to consider several factors in choosing a particular formulation, including
ease, frequency, and form of administration. The applicators for the creams and
the vaginal tablet are narrow enough for
most patients. Some studies have used
external application of the cream when
insertion of the applicator was not possible, although this is not an indicated
method of administration.
Frequency of administration and
The Female Patient | Vol 37 november/december 2012 37
Non-Sex-related Symptoms of Vulvovaginal Atrophy
dosage of the creams vary according to
the prescribed regimen. The tablet is
administered every day for the first 2
weeks and then biweekly thereafter. The
ring requires a certain amount of dexterity for insertion but only needs to be
replaced every 90 days. If a woman cannot self-insert the ring, she can see her
caregiver every 3 months for a replacement, enabling her to receive ongoing
local therapy. Finally, if total dosage is a
concern, the ultra-low-dose tablet (10 µg
estradiol), which replaced the 25-µg formulation, provides the smallest amount
of estradiol absorption.17
Anticipated Benefits of Local Vaginal
Estrogen
Local vaginal estrogen improves patient-reported symptoms of dryness and
itchiness and returns the tissues to a
healthier state with less paleness and
dryness noted on clinical examination.
It also restores vaginal pH to premenopausal levels, improves the vaginal maturation index, increases vaginal blood
flow, and enhances fluid secretions.4
The effects of estrogen on connective
tissue and smooth muscle are not read-
Table 3.
ily measured, but clinical examination
may be used to verify the restoration of
normal vaginal elasticity.
Urinary symptoms may also improve
with local vaginal estrogen administration.12 Vaginal estrogen has been shown
to cure or improve urinary incontinence11, 12 and reduce the incidence of
UTIs.6 Vaginal estrogen has also been
used to treat dysuria resulting from
urethral caruncles in postmenopausal
women, although no randomized controlled studies to investigate this practice have been conducted.
Following and Managing Women on
Local Vaginal Estrogen
Vulvovaginal atrophy is a chronic condition, and treatment usually must be
continued to prevent the return of symptoms, although some women can eventually use less medication. Patients generally see results within 4 to 8 weeks;
however, those with severe atrophy may
need additional time. The typical follow-up period is 2 to 3 months. Safety
data have been gathered up to 1 year,
and longer-term data are not currently
available.4 We suggest individualized
Local Estrogen Therapies for Vulvovaginal Atrophy
Product
Type of Estrogen
Recommended Dosing Regimen
Premarin® vaginal cream
Conjugated estrogens
(625 μg per g cream)
0.5 g cream twice weekly
or
0.5–2 g cream daily (21 days on, 7 days off)
Estrace® vaginal cream
Estradiol
(100 μg per g cream)
Initial: 2–4 g cream daily (1 or 2 weeks), reduced gradually
to half initial dosage (1 or 2 weeks)
Maintenance: 1 g, one to three times per week
Estring® vaginal ring
Estradiol
(7.5 μg released per 24 h)
1 ring replaced every 90 days
Vagifem® vaginal tablet
Estradiol
(10 μg per tablet)
Initial: 1 vaginal tablet daily (2 weeks)
Maintenance: 1 vaginal tablet twice weekly
Data from product package inserts.13-16
38
The Female Patient | Vol 37 november/december 2012
Minkin and Guess
therapy tailored to the patient’s wants
and needs.
Local Vaginal Estrogen Use in Breast
Cancer Patients
Vaginal estrogen therapy may be used
with caution in breast cancer patients,
in consultation with the patient’s oncologist and according to patient preference.18 Oncologists are often comfortable with therapeutics that provide a
very low, predictable release of estrogen,
although no general recommendations
can be made in the absence of large, randomized controlled trials.
Discussing the Risks and Benefits of
Local Vaginal Estrogen Use with Your
Patients
To provide the patient with a balanced
view of the risks and benefits of local
vaginal estrogen, the clinician should
discuss data pertaining to safety and
effectiveness. Many studies performed
over the past two decades show that
various formulations provide effective
relief of vulvovaginal dryness and itching, although the use of moderate to
high doses of the conjugated estrogens
cream has been associated with endometrial overstimulation, uterine bleeding, breast pain, and perineal pain.19
A low-dose regimen of the conjugated
estrogens cream has a better safety profile and, like the tablet and ring, does not
require coadministration of progestin.20
Additionally, it may be useful to explain
that steady-state plasma estradiol levels
on the ultra-low-dose tablet are similar
to baseline levels.17 For most women presenting with moderate to severe vulvovaginal atrophy, the potential benefits of
low-dose, local vaginal estrogen therapy
are significant while the risks appear to
be minimal.
Increasing Awareness of
Vulvovaginal Atrophy: Role of the
Clinician
A recent international study found that
American women are particularly vulnerable to embarrassment in discussing
their vulvovaginal discomfort, compared to women in other developed nations.1 Thirty-three percent of surveyed
American women aged 55 to 65 years
who experienced vaginal discomfort
had not discussed the issue with anyone. Of these women, 60% said that
talking about their vaginal discomfort
made them feel uncomfortable or embarrassed, 52% considered it a private
matter, 49% considered it to be a normal part of aging, and 20% preferred if
someone else (such as a provider) initiated the conversation. Only 26% of
American women who experienced vaginal discomfort as a result of menopause
were prescribed treatment. Of this pop-
FoCUSPOINT
Thirty-three percent of surveyed
American women aged 55 to 65 years
who experienced vaginal discomfort had
not discussed the issue with anyone.
ulation, 32% had waited a year or more
before seeking treatment, and 11% had
waited 3 or more years. All clinicians
who routinely care for postmenopausal
women should be aware of these communication issues and proactively encourage women to report any present or
future vulvovaginal discomfort.
The clinician, frequently the ObGyn,
plays a key role in identifying those patients with vulvovaginal atrophy who
might benefit from treatment and may
consider the following:
1.Adding questions about vulvovaginal
and urinary symptoms to intake paperwork
2.Direct questioning
3.Reflex questioning based on findings
of the physical exam.
If using direct or reflex questioning, it
The Female Patient | Vol 37 november/december 2012 39
Non-Sex-related Symptoms of Vulvovaginal Atrophy
may be useful to ask patients specifically about both vaginal and urinary symptoms, perhaps prefacing these questions
with a general statement such as, “Many
women experience vaginal dryness or
itching, pain with sex or urination, or
incontinence around and after menopause.” Routine gynecologic exams help
to diagnose patients experiencing these
symptoms and provide a venue for encouraging patients to seek treatment, if
appropriate.
FoCUSPOINTØ
Primary care physicians and urologists,
in particular, are encouraged to ask
women about discomfort in the lower
urinary tract and genitalia.
ever, that the International Classification
of Diseases (ICD) 9 coding does not include this term. Clinicians must instead
choose from the ICD-9 codes for “vulvar
atrophy” (624.1) or for “postmenopausal
atrophic vaginitis” (627.3). It is recommended that the latter code be applied
when symptoms are more generalized,
despite its false implication that an inflammatory process must be present.
Summary
Vulvovaginal atrophy is a common,
chronic disorder that affects many
postmenopausal women. Bothersome
sequelae, including dryness, itching,
irritation, and incontinence, and recurrent UTIs can be safely and effectively
managed with the use of local vaginal
estrogen therapy. However, a major challenge still exists in reaching the affected
population. ObGyns, as well as primary
care physicians and urologists, can help
by identifying symptomatic women, addressing their concerns, and counseling
them about available treatment options.
Acknowledgments
Primary care physicians and urologists, in particular, are encouraged to
ask women about discomfort in the lower urinary tract and genitalia. If primary
care physicians or urologists elicit a history of recurrent UTIs or other urinary
complaints, such as urgency or frequency, a physical exam can be performed
to evaluate for atrophy and, when indicated, therapy can be initiated. A consultation should be obtained from a urogynecologist, gynecologist, or urologist
with an interest in atrophic symptoms
if the provider is uncomfortable treating
women with these symptoms, for women in whom estrogen is contraindicated
or who are refractory to therapy.
Recommendations for
Documentation and Coding
The more inclusive term vulvovaginal
atrophy was selected for this article as
it best reflects the broad range of symptoms described. It should be noted how-
40
The Female Patient | Vol 37 november/december 2012
Editorial assistance was provided by Pamela Barendt, PhD, ETHOS Health Communications, Newtown, Pennsylvania,
with financial assistance from Novo
Nordisk, Inc, Princeton, New Jersey, in
compliance with international guidelines on Good Publication Practice.
The authors report no other actual or potential
conflicts of interest in relation to this article.
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