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Vaginal Atrophy

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					vaginal atrophy
DR/ AKRAM ABD ELGHANY
   M D , ALAZHAR UNIVERSITY
  CONSULTANT OBS.&GYN.
    PORTSAID G.HOSPIT
       EGYPT
• vaginal atrophy results in years of
  discomfort with a significant
  impact on quality of life.

• Unlike vasomotor symptoms of
  menopause, symptoms of vaginal
  atrophy are progressive and do not
  regress over time.
vaginal atrophy

•15% of premenopausal women.

•10-40% of postmenopausal.

•10-25% of those taking systemic
hormone therapy.
cultural and religious taboos
regarding sexuality,
menstruation and menopause
inhibits some women from
discussing vaginal dryness and
sexuality issues with health care
practitioners.
Etiology
• Menopause.
• Oophorectomy.
• postpartum loss of placental
  estrogen.
• breastfeeding, increased prolactin
  concentrations.
• radiation, chemotherapy.
• GnRH agonist analogs.
• anticholinergics, antihistamines,
  antipsychotics.
•cigarette smoking.
•chemical sensitivities (douches,
soaps, detergents, deodorants,
perfumes).

•miscellaneous causes (perineal
products, sanitary products,
tight-fitting or synthetic clothing,
nulliparity, cessation of coital
activity).
•Estrogen loss is the most
common cause of vaginal atrophy.
•Natural menopause and
oophorectomy are the usual
causes.
• urogenital atrophy in 17% of
women 4 weeks postpartum.
• Difficulty with intercourse in 45%
of postpartum women.
•Breastfeeding was associated
with dryness in 71% of nursing
mothers.

•Mothers using infant formulas
had a 17% frequency of vaginal
dryness.
•Premature ovarian failure due to
irradiation or chemotherapy can
produce functional menopause.

•Drugs can change hormone
concentrations, producing negative
pharmacologic effects or altering
microflora.
•Long-term therapy with GnRH agonist
decreases estrogen.

• Danazol suppresses the pituitary-
ovarian axis and have a direct
antiestrogen effect causing dryness.

•Tamoxifen's anti-estrogen effect also
cause dryness.
•The anticholinergic effects of
antihistamines, tricyclic antidepressants
and antipsychotics.

•Cigarette smoking is associated with
more advanced and earlier atrophic
changes on vaginal smears.
•smoking increases estrogen
metabolism.
• Antibiotics can change the vaginal
  microflora and cause some
  symptoms of urogenital atrophy.

• Radiation therapy produce
  changes in vaginal mucosa,
  fibrosis and vaginal stenosis from
  direct radiation effects and
  radiation castration.
Physiology
•The vaginal epithelium consists of
3 cell layers: superficial,
intermediate and basal capable of
storing glycogen under the
influence of estrogen.
•With elevated estrogen all levels of
the epithelium thicken as a result of
glycogen storage.
•With diminished estrogen the
layers become thin and atrophic.
•The vaginal lining is highly folded.
•respond cyclically to monthly
variations in hormone levels.
•contains no glands.
•Lubrication is produced by fluid
transudation from blood vessels
with some contribution from
endocervical and Bartholin's
glands.
•Before menopause, the vaginal
pH 3.5-4.5. Low pH is maintained
by the glycogen.

•Glycogen is converted to lactic
acid by normal vaginal flora.
•An acidic pH discourages growth
of pathogenic bacteria.
•the bacterial flora of the healthy
vagina contains aerobic and
anaerobic, gram positive and gram
negative bacteria.
•Lactobacillus and Corynebacterium
predominate over other bacteria
such as Streptococcus,
Bacteroides, Staphylococcus and
Peptostreptococcus.
•Both Lactobacillus and
Corynebacterium produce lactic
and acetic acid from glycogen, thus
maintaining the low vaginal pH.
•Additional bacteria are kept in
check by the acid-producing
bacteria and are rarely pathogenic,
but they may become pathogenic if
the environmental balance is
affected.
•Hormones are important in
maintaining vaginal health.

•Estrogen receptors are present in the
vagina and labia minora.
•progesterone receptors in the vagina.
•androgen receptors in the vagina,
labia minora, labia majora and
suprapubic tissues.
Pathophysiology
•With estrogen loss vaginal epithelium
appear thin, pale and normal rugation
lost.
•Decreased subcutaneous fat and scant
lubrication.
• Vaginal pH becomes more alkaline (>
5.0) resulting in alterations in normal
flora and increased susceptibility to
infection.
•the bladder and urethra become
atrophic, causing urinary frequency and
incontinence.
•A vaginal smear is the diagnostic
standard for vaginal atrophy.
• the superficial cell layer is thin.
•amount of parabasal cells is
increased and underlying collagen
tissue is compact.
•The maturation index is the
proportion of parabasal,intermediate
and superficial cells counted from
each 100 cells on a smear.
•During the perimenopausal period,
estrogen secretion, primarily
estradiol, remains at approximately
120 ng/L.
•After menopause, it decreases to
approximately 18 ng/L.

•The reduction of estrogen causes
thinning of the epithelium and a
diminished glycogen content.
•In premenopausal women, the
maturation index is 0 parabasal, 40-
70 intermediate, and 30-60
superficial cells depending on cycle
phase
•During early menopause,
parabasal cells increase to 65 and
intermediate and superficial cells
decrease to 30 and 5, respectively.
• Vaginal pH may be a surrogate
  marker for urethral
  estrogenization.

• A thin endometrium measuring
  4-5 mm on ultrasound reveals
  inadequate estrogenization.
Symptoms
•Vaginal atrophy may be
symptomatic in up to 40% of
postmenopausal women.
• most women do not seek
medical attention for these
symptoms.
• Dryness is the most common
symptom of vaginal atrophy.
•vaginal soreness.
•postcoital burning.
•Dyspareunia.
•burning leukorrhea.

•vaginal spotting results from a
break in the thin vaginal mucosa.

•Dyspareunia result from ulceration
of the vulvovaginal epithelium
•difficulty in sexual arousal.
•burning sensation.
•malodorous discharge.
•vaginal irritation.

•Dryness and irritation, coupled
with inability to lubricate the
vagina sufficiently during
intercourse, can result in
dyspareunia.
• Anxiety associated with the
  expectation of pain can
  compound the problem.
  vaginismus (painful spasm of
  vaginal muscles) can occur.
• urinary symptoms such as
  dysuria, hematuria, urinary
  frequency, urinary tract infections
  and incontinence.
SIGNS
• The external genitalia involved
  with dryness, shrinking and
  leukoplakic patches on the
  mucosa.
• thinning and graying pubic hair.
• thinning and pallor of tissue.
• diminution of the labia minor.
• the presence of petechiae.
• The vaginal walls is thin, pale and
  smooth.
• atrophy of the subcutaneous
  tissues cause shortening and
  narrowing of the vaginal.
• Basal epithelial cells, reflecting
  estrogen deficiency, predominate
  on cytologic analysis.
• The cervix atrophies and the os
  become stenosed.
• The uterus significantly decreases in
  size.
• the endometrium is thin and atrophic.

• the myometrium is replaced by
  fibrous tissue.
• the ovaries cannot normally be
  palpated on bimanual pelvic
  examination.
•The vagina is thin, with occasional
petechia and diffuse redness with
few or no vaginal folds.
•A serosanguinous discharge.
• pH of 5-7.
• A wet mount shows white blood
cells and a paucity of Lactobacillus.
Treatment
•First-line therapy for women
with vaginal atrophy includes
nonhormonal vaginal lubricants
and moisturizers.
• Women should also be
encouraged to continue sexual
activity.
Nonpharmacologic Therapies
• Sexual activity is associated with
  maintaining vaginal health in
  postmenopausal women.
• Masturbation maintains vaginal
  secretions and elasticity.
• Stress-reduction therapy and
  psychological counseling benefit
  women with nonorganic causes of
  vaginal dryness.
          Lubricants
• Lubricants are temporary measures
  to relieve vaginal dryness during
  intercourse.
• Short durations of action limit their
  usefulness as a long term solution.
• Lubricants must be applied
  frequently for more continuous relief
  and require reapplication before
  sexual activity.
      Moisturizers
• Replens claim to moisturize the
  vagina and provide more than
  transient lubrication.

• providing long term relief of
  vaginal dryness rather than being
  just sexual aids.
    Herbal Products
• Ten percent of women use herbal
  remedies to treat postmenopausal
  symptoms.

• Controlled trials of black cohosh
  showed consistent improvement
  in menopause symptoms.
• no change or stimulation of
  vaginal epithelium.
• Dong quai treatment was not
  effective in relieving menopause
  symptoms and did not change
  endometrial thickness or vaginal
  maturation index.
• Phytoestrogen supplementation
  with soy protein 60 g/day did not
  change vaginal maturation index,
  but 20 g/day improved vasomotor
  symptoms.
• Chaste tree extracts contain
  progesterone,hydroxyprogesterone,
  and androstenedione. It is widely
  used in Germany to treat breast
  pain, ovarian insufficiency and
  uterine bleeding, but has not been
  specifically studied for vaginal
  dryness.
 Estrogen replacement therapy
• restore vaginal cytology.
• decrease vaginal pH to
  premenopausal levels.
• increase vaginal fluid secretions,
  mucosa thickness, blood flow
  and sensorimotor response.
• restore vaginal flora similar to
  premenopausal conditions.
• provide symptomatic relief.
 Additional benefits are relief of
 other menopause symptoms.

• improvements in urinary
  frequency and incontinence.

• positive effects on bone density,
  fractures and lipids.
      Oral Estrogens
• The lowest dosage required to
  treat urogenital atrophy is unclear.

• Continuous or intermittent intra-
  vaginal therapy may be required
  for women receiving systemic
  hormone therapy with unresolved
  urogential atrophy.
estriol tablets decreasing from 8 to 2
mg/day improved the maturation
index by the fourth week.
Estriol 3 mg/day for 1 month followed
by 1 mg/day for 1 month changed
vaginal microflora from fecal-type to
lactobacilli.
This regimen converted the thin, dry
vaginal mucosa to a thicker, well-
vascularized, more secretive mucosa.
   Transdermal Estrogens
• effective in relieving symptoms.
• Four dosages of transdermal estradiol,
  25, 50, 100, and 200 µg/24 hours.
• progestins should be added to the
  regimen for women with an intact
  uterus.
• The estradiol-norethindrone
  transdermal patch is FDA approved for
  vulvar and vaginal atrophy.
Intravaginal Estrogens
Local and systemic effects are
seen with intravaginal estrogen.
Absorption of conjugated equine
estrogens, estradiol and estriol
across the vaginal mucosa is
rapid. Systemic bioavailability is
high, since the first-pass effect
through the liver is avoided.
    Vaginal Creams
• Conjugated equine estrogens,
  estradiol, and estriol creams restore
  vaginal cytology to premenopausal
  levels and improve urogenital
  atrophy.
• Creams are absorbed into systemic
  circulation, with higher dosages
  resulting in higher estrogen level.
    Vaginal Tablets
• A 25-µg 17b-estradiol vaginal tablet
  was approved by the FDA.
• one tablet every day for 2 weeks,
  followed by one tablet twice/week.
• Estradiol concentrations increased
  but estrone concentrations did not
  change.
• improvements in vaginal cytology,
  dryness and dyspareunia.
The 17ß-estradiol tablets were
equal in efficacy but preferred over
creams.

Compared with conjugated equine
estrogen cream 1.25 mg/day,
decreases in vaginal atrophy and
symptoms were similar.
• women using the vaginal tablet had
  fewer estradiol concentrations above
  normal postmenopausal
  concentrations.
• fewer adverse events (9% vs 34%).
• fewer withdrawals (10% vs 32%).
• one patient had a proliferative
  endometrium.
• two women in the cream group had
  endometrial hyperplasia.
•The most commonly reported
adverse effects associated with
vaginal estrogen therapy are

•vaginal bleeding.
• breast pain.
• nausea and perineal pain
reported less frequently
      Vaginal Rings
• FDA approved for treatment of
  vaginal atrophy and lower urinary
  tract symptoms.
• flexible 2-mg silicone rings deliver
  estradiol 7.5 µg/day at a sustained
  rate for up to 12 weeks.
• The rings are 55 mm in diameter
  and 9 mm thick, with a 2-mm
  estradiol core.
• The average estradiol
  concentration after 4 weeks of
  insertion, during which the
  estimated release of estradiol was
  0.35 ± 0.07 mg, was 32 ± 28
  pmol/L and estrone concentration
  was 178 ± 70 pmol/L.
Although the vaginal ring is comparable
with estrogen creams and pessaries,
women preferred the ring.
The ring and conjugated equine
estrogen cream 0.625 mg/day for 12
weeks were similarly successful in
improving vaginal cytology, decreasing
pH, and curing vaginal atrophy.

The ring was rated good to excellent by
84% of users and the cream by 43%.
Vaginal Suppositories
• Estriol suppositories 0.5 mg every
  night for 2 weeks and then
  twice/week resulted in 98% cure
  of atrophic vaginitis after 1 year.

• fewer gram-negative organisms
  in urine cultures.
• After 8 weeks of therapy, the
  maturation index increased from
  0.5 to 16.5, changes lower than
  those with estriol vaginal cream.

• A suppository containing estradiol
  250 µg and progesterone 10 mg
  increased estrone, estradiol, and
  progesterone serum
  concentrations after one dose.
Synthetic Hormone Products

• Tibolone is synthetic hormone
  product with weak estrogenic,
  progestagenic and androgenic
  activity.
• It increased the maturation index
  and improved symptoms of
  vaginal atrophy.
   Patient Counseling
• Women considering ERT should be
  counseled on the benefits and risks of
  treatment.
• Estrogen is contraindicated in.
• pregnant women.
• breast or estrogen-dependent cancer.
• undiagnosed abnormal vaginal
  bleeding.
• active liver disease, chronic impaired
  liver function.
• active thrombophlebitis or history
  of thromboembolic disorders.

• Relative contraindications include
 seizures, hypertension, uterine
  leiomyomas, hyperlipidemia,
  migraine, endometriosis, and
  gallbladder disease.
• Estrogen therapy is controversial in
women with a history of endometrial
cancer.
•most clinicians prescribe it if the patient
has had a hysterectomy and metastatic
disease did not exist.
• A progestin should be added to the
regimen for women with an intact uterus
to prevent the 4- to 8-fold increased risk
of endometrial cancer linked with
unopposed estrogen.
• Progestin is not necessary with
  the estradiol ring and vaginal
  tablets and might not be
  necessary with ultra-low-dosage
  (12.5 µg/day) transdermal
  patches.
• Women unwilling or unable to
  take a progestin require an
  annual endometrial biopsy.
adverse effects of systemic
     estrogen therapy
• breast tenderness and enlargement.
  vaginal bleeding or spotting.
• nausea and slight weight gain.
• Breast tenderness decreases with time.
• Taking the oral product with food
  prevent nausea.
• Patches cause local irritation at
  application sites.
    adverse effects of intra-
       vaginal products
• local burning and genital pruritus.
• spotting.
• The most common adverse effect
  is vaginal secretion.
• if the discharge has a bad odor
  or is associated with vaginal
  itching or other signs of vaginal
  infection, further evaluation is
  warranted.
    Specific
recommendations
Local estrogen therapy is the
most accepted treatment of
vaginal atrophy
Local estrogen therapy

•effective for symptoms of
vaginal atrophy.
• not effective for the
management of vasomotor
symptoms.
•cannot reduce the risk for
osteoporosis
• subjective improvement occurs in
80% to 90% of women treated with
local vaginal estrogen.
• Vaginal atrophy unresponsive to
estrogen may be due to undiagnosed
dermatitis or vulvodynia.
•treatment failure warrants future
evaluation and careful examination.
•Low-dose vaginal estrogen for
treating vaginal atrophy include
estradiol cream, conjugated estrogens
cream, the estradiol ring, and the
estradiol hemihydrate vaginal tablet.
•These are equally effective.
•so specific choice depends on clinical
experience and patient preference.
Closer surveillance required for
•women at high risk for endometrial
cancer.
•higher dose of vaginal estrogen
therapy.
•spotting or breakthrough bleeding.
•Evidence is insufficient to
recommend annual endometrial
surveillance in asymptomatic women
using vaginal estrogen therapy.
•Women with hormone-dependent
cancer are not ideal candidates for
treatment with local estrogen.

•women with severe symptoms not
improved with conservative
measures may be considered for
vaginal estrogen therapy.

				
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