Treatment of Atrophic Vaginitis

REVIEW

Treatment of atrophic vaginitis

Camil Castelo-Branco† Up to 40%of postmenopausal women have symptoms of atrophic vaginitis. Since the & Fabiola Rostro condition is attributable to estrogen deficiency, it may also occur in premenopausal †Author for correspondence women who take antiestrogenic medications or who have medical or surgical conditions Institut Clínic de Ginecologia, Obstetrícia i that result in decreased levels of estrogen. The thinned vaginal epithelium and increased Neonatologia, Hospital vaginal pH level induced by estrogen deficiency predispose the vagina and urinary tract to Clínic, Facultad de infection and mechanical weakness. The earliest symptoms are decreased vaginal Medicina, Universidad de Barcelona, C/ Villarroel 170 lubrication, followed by other vaginal and urinary symptoms, such as dryness, burning, 08036 Barcelona, Spain itching and dyspareunia, which may be exacerbated by superimposed infection. These E-mail: castelobranco@ symptoms can contribute to sexual dysfunction, loss of sexual intimacy and may have a ub.edu negative impact on overall quality of life. Once other causes of symptoms have been eliminated, treatment usually depends on estrogen replacement. Estrogen-replacement therapy decreases vaginal pH, thickens and revascularizes the vaginal epithelium, increases the number of superficial cells and reverses vaginal atrophy, and may be provided systemically, if symptoms are severe or affect quality of life, or locally; however, the dosage and delivery method must be individualized. Vaginal moisturizers and lubricants, and participation in coitus, may also be beneficial in the treatment of women with atrophic vaginitis.

Menopause is related to histological and func- opportunity to improve the urogenital health tional changes owing to a decline in both follicu- and quality of life (QoL) of a large patient pop- lar development and ovarian function. The ulation through identification of and interven- resulting estrogen deprivation causes menopau- tion in this often overlooked and sal symptoms that include hot flushes, menstrual underdiagnosed condition. irregularities, night sweats, insomnia, headache, The vagina, vulva, urethra and trigone of the anxiety, dizziness, nervousness, depression, irrita- bladder all contain estrogen receptors and bility, diminished libido, fatigue, gastrointestinal undergo atrophy when estrogen levels decrease. upset and urinary difficulties [1–6]. This results in decreased vaginal secretion and Atrophic vaginitis (AV) occurs as a result of a susceptibility to trauma and pain. The vaginal significant decrease in estrogens levels. When epithelium becomes dry, atrophic and loses elas- levels of estradiol are decreased, vaginal tissue ticity [9,10], which may cause inflammation, itch- becomes thinned, and this situation can be ing, burning, dryness, bleeding, spotting, observed in menopause and some other condi- dysuria, dyspareunia [3], urinary incontinence tions with low estrogen levels, including breast- and recurrent urinary tract infections [10,11]. The feeding, ooforectomy before the age of natural vulvar skin becomes thinner, the labia flattens menopause and use of gonadotropin-releasing and shrinks and the clitoris, uterus and ovaries hormone (GnRH) analogues. decrease in size [1]. Vaginal dryness is not limited Unlike vasomotor symptoms that resolve with to postmenopausal women; 15% of premeno- time, urogenital symptoms do not improve and pausal women and 10–25% of women receiving may actually worsen after the menopause [7]. systemic HT experience it [9]. Treatment for these symptoms has been based More than 50% of postmenopausal women on systemic and local hormonal therapy (HT), experience moderate or severe symptoms related and proved to be successful. However, this ther- to atrophic modifications in the genitourinary Keywords: hormonal therapy, [9] local therapy, menopause, apy is contraindicated in some women and is not tract . These symptoms can contribute to sexual vaginitis accepted by others. dysfunction and loss of sexual intimacy [12,13] and Despite the prevalence of symptoms, only may have a negative impact on overall QoL [14]. part of 20–25% of symptomatic women seek medical Dyspareunia leads to decreased interest in coi- attention [8]. Therefore, physicians have an tus and, as the frequency of coitus diminishes,

vaginal lubrication declines further [15]. strip in the vaginal vault may also be a sign of Although cultural differences affect the fre- vaginal atrophy. On microscopic evaluation, quency of, and distress caused by, menopausal loss of superficial cells is obvious with atrophy. symptoms [16], a decrease in sexual desire was reported in 90% of Chinese and 67% of North Treatment American women, corresponding to ranks of one A number of strategies have been proposed in and four out of 25 symptoms, respectively. relation to AV; however, an agreement exists Cigarette smoking is strongly associated with regarding the management and therapy of this worsened vaginal atrophy – smokers also have an condition (Box 1). The common treatment until earlier age of natural menopause and a greater the 1990s was systemic HT if symptoms are proportion of them experience atrophy right severe or affect QoL, but this treatment has from the beginning of menopause. Smoking has been consequently reconsidered due to its a direct effect on the vaginal squamous epithe- adverse effects. Topical estrogenic products lium, [17] reduces estrogen bioavailability [18] and have subsequently been developed to minimize diminish blood perfusion [19]. the systemic adverse effects of the oral HTs. More attention must be focused on the prob- Estrogen therapy decreases vaginal pH, thick- lems faced by women post menopause since an ens and revascularizes the vaginal epithelium, increasing number of women will spend increases the number of superficial cells and approximately a third to a half of their life in reverses vaginal atrophy [3]. the postmenopausal period. This is due to the Estrogen or combined HT (estrogen–pro- fact that the age of spontaneous menopause in gestin) is highly efficacious for managing the European countries is between 46.9 and 50.1 signs and symptoms of urogenital atrophy [9]. years [20] and women’s life expectancy has All routes are effective, including systemic and increased significantly. local estrogen replacement. Various forms of estrogen-based therapies have been shown to Diagnosis effectively manage menopausal signs and Increased clinical suspicion is the first step in symptoms, including those associated with the diagnosis of vaginal atrophy, which will vaginal atrophy [1–6]. prompt the initiation of safe therapies with Lower-dose estrogen therapy provides thera- proven efficacy. The diagnosis is based on phys- peutic efficacy while minimizing adverse effects. ical examination and laboratory findings. Dur- Literature supports the use of low doses of estro- ing the examination, atrophic epithelium gen therapy for effectively relieving symptoms appears pale, smooth and shiny. Often, inflam- and restoring healthy vaginal cytology in post- mation with patchy erythema, petechiae and menopausal women with vaginal atrophy, but increased friability may be present. External even these low-dose therapies should be opposed genitalia show diminished elasticity, ther is less by occasional progestogen to prevent endome- turgor in the skin, a sparsity of pubic hair, dry- trial carcinoma. Currently, the tendency is to use ness of the labia, vulvar dermatoses, vulvar the effective minimum dose that combines the lesions and fusion of the labia minora [8], and largest therapeutic effect with the minimum this friable and poorly rugated vaginal epithe- adverse effects. In a Cochrane revision, it was lium is more prone to traumatic damage. found that there is strong and consistent evi- Ecchymoses and minor peri-introital lacera- dence that unopposed estrogen therapy, at mod- tions may also occur after coitus or during a erate and high doses, is associated with increased speculum examination, resulting in vaginal rates of endometrial hyperplasia, irregular bleed- bleeding spotting. ing and consequent nonadherence to therapy. Laboratory findings include follicle-stimulat- The addition of oral progestogens, administered ing hormone (FSH) and luteinizing hormone either sequentially or continuously, is associated (LH) increased serum levels and decreased with reduced rates of hyperplasia and improved estradiol levels. Papanicolaou smear can con- adherence to therapy. Irregular bleeding is less firm the presence of urogenital atrophy. Cyto- likely under sequential than continuous therapy logic examination of the smears shows an during the first year of treatment, but there is a increased proportion of parabasal cells and a suggestion that continuous therapy over a long decreased percentage of superficial cells (a high duration is more protective than sequential ther- maturation index [MI] value). An elevated pH apy in the prevention of endometrial hyperpla- level (exceeding 4.5) [21] monitored by a pH sia. Hyperplasia is more likely when progestogen

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Box 1. Recommendations in the detection, management and Vaginal tablet therapy resulted in greater treatment of atrophic vaginitis. patient acceptance and lower withdrawal rates compared with vaginal cream therapy. • Lifestyle: increase sexual activity Mainini and colleagues observed that low- • Homeopathic remedies, such as byronia, lycopodium and belladonna, dose 17β-estradiol vaginal tablets in the treat- administered as supplements may play a minor role ment of postmenopausal AV constitutes an • Astroglide and other lubricants may be used (take into account whether extremely valid approach in terms of effectiveness they are compatible with latex condoms if safe sex is a consideration) and safety [28]. • Complementary and alternative treatments may also play a minor role, such as Chinese herbs and acupuncture Speroff observed that a ring containing an • Polycarbophilic gels estradiol acetate core improves the vaginal MI • Vitamin E, D oil, cream or capsules in 97.5 compared with 70% of patients with a • Drugs: vaginal estrogen or systemic hormone therapy placebo ring. Self-reported symptoms of vaginal dryness and dyspareunia improved, as did is administered every 3 months in a sequential the sexual dysfunction subscale of the Greene regimen compared with a monthly progestogen Climacteric questionnaire [29]. Marketed rings sequential regimen [22]. in the USA include a ring for systemic and vag- Transdermal estradiol therapy, whether by inal menopausal therapy that provides average patch or gel, also results in vaginal symptom serum estradiol levels of 40.6 pg/ml for the improvement; it has been shown to relieve vaso- 0.05-mg and 76 pg/ml for the 0.1-mg dose, motor symptoms and cause a significant shift in and a ring for urogenital menopausal symp- the vaginal MI compared with placebo [23,24]. toms only that minimally elevates serum estra- Vaginal estrogen preparations are safe and diol, usually within the menopausal range, effective treatments in patients with vaginal treating AV and urethritis. Vaginal rings offer a atrophy who are not candidates for systemic novel approach to menopausal HT producing HT; alternatives include creams, pessaries, tab- consistent serum levels sustained for up to lets and the estradiol-releasing vaginal ring that 3 months per unit dose with lower adverse appeared to be equally effective in treating the effects than other vaginal products and high symptoms of vaginal atrophy with significant acceptability among users [30]. differences compared with placebo and non- In some cases, topical estrogenic products are hormonal gel according to a Cochrane review still considered at risk in case of prolonged use including 19 trials of 4162 women [25]. One trial and some women cannot or do not want to use found significant side effects following cream them, therefore, they may use water-soluble vagi- (conjugated equine estrogen) administration nal lubricants and vaginal moisturizers applied on when compared with tablets causing uterine a regular basis that have an efficacy equivalent to bleeding, breast pain and perineal pain. Another local HT in relieving vaginal dryness [31]. trial found significant endometrial overstimula- As an alternative, two clinical trials were per- tion following use of the cream (conjugated formed to investigate the effects of a medical equine estrogen) when compared with the ring. device in the form of a gel, containing As a treatment choice, women appeared to favor hyaluronic acid, liposomes, phytestrogens from the estradiol-releasing vaginal ring for ease of Humulus lupulus extract and vitamin E. This use, comfort and overall satisfaction. device could be considered an effective and safe Rioux and colleagues found that treatment alternative treatment for genital atrophy in regimens with 25-µg 17β-estradiol vaginal tab- postmenopausal women, especially when HT lets and with 1.25-mg conjugated equine is not recommended [32]. However, alone, these estrogen vaginal cream were equivalent in products are not a solution for AV. relieving symptoms of AV [26]. The vaginal tablets demonstrated a localized effect without Sexual activity appreciable systemic estradiol increases or Sexual activity is a healthy prescription for estrogenic side effects. postmenopausal women. It has been shown to In another study, the vaginal estradiol tablet, encourage vaginal elasticity and pliability, and Vagifem®, significantly raised systemic estradiol initiate a lubricative response. Women who levels, at least in the short term [27]. This reverses participate in sexual activity report fewer the estradiol suppression achieved by aromatase symptoms of AV and, on vaginal examination, inhibitors in women with breast cancer and is have less evidence of stenosis and shrinkage in contraindicated in those cases. comparison with sexually inactive women. A

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negative relationship exists between coital Johnston and colleagues recommended that activity, including masturbation, and symp- healthcare providers routinely assess postmen- toms of vaginal atrophy [8]. Coitus is not opausal women for the symptoms and signs of hypothesized to restore or maintain estrogen in vaginal atrophy, a common condition that postmenopausal women because no positive exerts significant negative effects on QoL. relationship has been shown to exist between Regular sexual activity should be encouraged estrogen levels and sexual activity. The exist- to maintain vaginal health and should be ence of a positive relationship between coital offered to women wishing to avoid use of activities and both gonadotropins and andro- hormone-replacement therapy [31]. gens demonstrates the importance of these compounds to healthy vaginal epithelium Conclusion when estrogen levels are decreased. AV is the result of a significant decrease in estrogens levels. When levels of estradiol are Executive summary decreased, vaginal tissue becomes atrophic and common vaginal symptoms appear and tend to • Up to 40%of postmenopausal women have symptoms of worsen with age, having a significant impact on atrophic vaginitis. sexuality and QoL. The use of HT in both local • Atrophic vaginitis is linked to estrogen deficiency and is not only related to and systemic administration has been shown to postmenopausal status. effectively manage menopausal signs and symptoms, including those associated with vaginal • The atrophy of the epithelium and an increase in vaginal pH predispose atrophy and, if this therapy cannot be used or is the vagina and urinary tract to infection and mechanical injury. refused, water-soluble vaginal lubricants and • Decreased vaginal lubrication, dryness, burning, itching and vaginal moisturizers can be an option. dyspareunia, the most common symptoms, can contribute to sexual dysfunction, loss of sexual intimacy and may have a negative impact on Future perspective quality of life. Since vaginal atrophy typically develops so • Estrogen-replacement therapy decreases vaginal pH, thickens and slowly that a woman may not notice any symp- revascularizes the vaginal epithelium, increases the number of superficial toms until 5–10 years after menopause begins, cells and reverses vaginal atrophy prevention policies will be mandatory in the next few years. Vaginal lubricants, topical estro- • Vaginal moisturizers and lubricants and participation in coitus may also be beneficial in the treatment of women with atrophic vaginitis. gens and regular sexual activity should be encouraged to patients.

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