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.