vaginal atrophy

1
vaginal atrophy

• DR/ AKRAM ABD ELGHANY
• M D , ALAZHAR UNIVERSITY
  CONSULTANT OBS.GYN.
• PORTSAID G.HOSPIT
• EGYPT

2

• 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.

3

• vaginal atrophy
• 15 of premenopausal women.
• 10-40 of postmenopausal.
• 10-25 of those taking systemic hormone therapy.

4

• cultural and religious taboos regarding
  sexuality, menstruation and menopause inhibits
  some women from discussing vaginal dryness and
  sexuality issues with health care practitioners.

5
Etiology
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• Menopause.
• Oophorectomy.
• postpartum loss of placental estrogen.
• breastfeeding, increased prolactin
  concentrations.
• radiation, chemotherapy.
• GnRH agonist analogs.
• anticholinergics, antihistamines, antipsychotics.

7

• 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).

8

• 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.

9

• Breastfeeding was associated with dryness in 71
  of nursing mothers.
• Mothers using infant formulas had a 17 frequency
  of vaginal dryness.

10

• Premature ovarian failure due to irradiation or
  chemotherapy can produce functional menopause.
• Drugs can change hormone concentrations,
  producing negative pharmacologic effects or
  altering microflora.

11

• 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.

12

• 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.

13

• 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.

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Physiology
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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

20

• 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.

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Pathophysiology
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• With estrogen loss vaginal epithelium appear
  thin, pale and normal rugation lost.
• Decreased subcutaneous fat and scant lubrication.
• Vaginal pH becomes more alkaline (gt 5.0)
  resulting in alterations in normal flora and
  increased susceptibility to infection.
• the bladder and urethra become atrophic, causing
  urinary frequency and incontinence.

23

• 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.

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• 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.

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• 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.

26

• Vaginal pH may be a surrogate marker for urethral
  estrogenization.
• A thin endometrium measuring 4-5 mm on ultrasound
  reveals inadequate estrogenization.

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Symptoms
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• 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.

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• 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

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• 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.

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• 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.

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SIGNS
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• 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.

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• 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.

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• 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.

36

• 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.

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Treatment
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• First-line therapy for women with vaginal atrophy
  includes nonhormonal vaginal lubricants and
  moisturizers.
• Women should also be encouraged to continue
  sexual activity.

39
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.

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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.

41
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.

42
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.

43

• 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.

44

• Chaste tree extracts contain progesterone,hydroxyp
  rogesterone, 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.

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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.

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• Additional benefits are relief of other
  menopause symptoms.
• improvements in urinary frequency and
  incontinence.
• positive effects on bone density, fractures and
  lipids.

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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.

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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.
49
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.

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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.

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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.

52
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.

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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.
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• 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.

55

• The most commonly reported adverse effects
  associated with vaginal estrogen therapy are
• vaginal bleeding.
• breast pain.
• nausea and perineal pain reported less
  frequently

56
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.

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• 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.

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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.
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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.
  

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• 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.

61
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.

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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.

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• active thrombophlebitis or history of
  thromboembolic disorders.
• Relative contraindications include
• seizures, hypertension, uterine leiomyomas,
  hyperlipidemia, migraine, endometriosis, and
  gallbladder disease.

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• 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.

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• 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.

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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.

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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.

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Specific recommendations
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Local estrogen therapy is the most accepted
treatment of vaginal atrophy
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• Local estrogen therapy
• effective for symptoms of vaginal atrophy.
• not effective for the management of vasomotor
  symptoms.
• cannot reduce the risk for osteoporosis

71

• 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.

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• 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.

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• 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.

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• 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.