{"paper_id":"a8db2ab5-7160-4e81-bb05-0ccee95c40e6","body_text":"Przegl¥d menoP auzalny 5/2013\n434\nAddress for correspondence: \nProf. Mirosław Wielgoś, Pl. Starynkiewicza 1/3, 02-015 Warszawa, Poland, tel. +48 22 502 14 30, e-mail: miroslaw.wielgos@wum.edu.pl\nDOI: 10.5114/pm.2013.38600\nSummary\nImprovement of living conditions and advances in medicine throughout the last few decades have led to \nprolonged life expectancy. Unfortunately, inevitable physiological processes of ageing cause burdensome changes \nresponsible for worsening of the quality of life of postmenopausal women. Many of these changes are linked to \nthe loss of ovarian hormonal activity. Complaints resulting from a decline in the estrogen level and symptoms in-\nvolving the lower genitourinary tract in postmenopausal women usually progress with time. They emerge from loss \nof vaginal epithelium thickness and elasticity, increase in pH of vaginal discharge as well as shift from physiologi-\ncal vaginal microflora with prevailing Lactobacillus spp. to abnormal milieu with dominance of other frequently \nanaerobic microorganisms. To relieve often severe symptoms of urogenital atrophic changes non-hormonal as well \nas hormonal treatment methods are available. Vaginal moisturizers and lubricants as well as systemic hormone \ntherapy are treatment options to be considered. Local estrogen therapy remains the first choice therapy in women \nwith no contraindications to estrogen administration. It is an effective and safe method of relieving symptoms \nof urogenital atrophy. There are different preparations of estrogens for local therapy available. A combination of \nestrogen and Lactobacillus cultures is an option worth considering. Early treatment allows for maintaining healthy \nvaginal microflora, which prevents development of distressing symptoms that decrease the quality of life.\nKey words: atrophic vaginitis, postmenopause, local estrogen therapy, vaginal microflora.\nStreszczenie\nPostęp medycyny oraz poprawa warunków życia w ciągu ostatnich dziesięcioleci spowodowały wydłużenie \nprzeciętnej długości życia. Nieuchronne procesy fizjologiczne związane ze starzeniem pogarszają jakość życia \nkobiet po menopauzie. Wiele z objawów związanych jest z zanikiem czynności hormonalnej gonad. Wynikające \nz tego objawy atrofii w obrębie dolnego odcinka dróg moczowo-płciowych u kobiet w wieku pomenopauzalnym \nzazwyczaj pogłębiają się w miarę upływu czasu. Wiążą się one z wynikającym z niedoboru estrogenów scień-\nczeniem i utratą elastyczności nabłonka pochwy, wzrostem odczynu pH i zastąpieniem fizjologicznej flory, jaką \nstanowią pałeczki kwasu mlekowego przez inne bakterie, często z przewagą beztlenowców. W chwili obecnej \nw łagodzeniu i leczeniu dolegliwości związanych z atrofią urogenitalną dysponujemy zarówno niehormonalny-\nmi, jak i hormonalnymi metodami leczenia. Zastosowanie znajdują preparaty nawilżające i lubrykanty, a także \nsystemowa terapia hormonalna. Leczeniem pierwszego wyboru u kobiet bez przeciwwskazań do terapii estro-\ngenowej pozostaje miejscowe zastosowanie estrogenów. Stanowi ono skuteczną i bezpieczną metodę leczenia \nuciążliwych objawów atrofii urogenitalnej u kobiet. Na rynku dostępne są różne preparaty do miejscowej terapii \nestrogenowej. Wartą rozważenia opcją terapeutyczną jest zastosowanie preparatów estrogenów w kombinacji \nze szczepami Lactobacillus. Odpowiednio wcześnie rozpoczęta terapia oraz zastosowanie dawek podtrzymują-\ncych pozwala na utrzymanie prawidłowego mikrośrodowiska w pochwie, co zapobiega rozwojowi uciążliwych \nobjawów istotnie pogarszających jakość życia.\nSłowa kluczowe: zanikowe zapalenie pochwy, postmenopauza, miejscowa terapia estrogenowa, mikroflora \npochwy.\nAtrophic vaginitis: symptoms, diagnosis and treatment\nZanikowe zapalenie pochwy: objawy, diagnostyka i leczenie\nMirosław Wielgoś, Natalia Mazanowska, Bronisława Pietrzak\n1st Chair and Department of Obstetrics and Gynecology, Medical University of Warsaw; \nHead of Department: Prof. Mirosław Wielgoś MD, PhD\nPrzegląd Menopauzalny 2013; 17 (5): 434-437\n\nPrzegl¥d menoP auzalny 5/2013\n435\nIntroduction\nThroughout the last few decades, improvement of \nliving conditions and advances in medicine have led \nto prolonged life expectancy. A small or even nega-\ntive population growth rate observed in the majority \nof developed countries means that the share of elderly \npeople in the ageing general population significantly \nincreases with a high prevalence of postmenopausal \nwomen. They are often fully physically and mentally fit \nand wish to lead an active lifestyle. \nInevitable physiological processes of ageing unfortu-\nnately cause burdensome changes responsible for wors-\nening of the quality of life. Many of them are linked to \nthe loss of ovarian hormonal activity. Main complaints in \npostmenopausal women are vasomotor symptoms and \nurogenital atrophy resulting from a decline in the estro-\ngen level. Whereas vasomotor symptoms tend to resolve \nwith age, urogenital atrophy typically develops later in \nlife and is often progressive. The lack of estradiol pro-\nproliferative effect on the epithelium of the vagina, ure-\nthra as well as the lower part of the cervix is noticeable \nin every third female in perimenopause and over 50% of \npostmenopausal women [1].\nInfluence of estrogens on vaginal milieu\nIn the premenopausal state, vaginal epithelium is \ninfluenced by high estradiol levels, stimulating cell mat-\nuration up to the superficial layer. Superficial epithelial \ncells continuously exfoliate and die, releasing glycogen, \nthat breaks down to glucose. Glucose is metabolised by \nspecies of Lactobacillus to lactic acid and H\n2O2, which \nallows for maintaining of normal vaginal microflora. \nThe coexistence of estrogenic activity and Lactobacilli \nleads to acidic vaginal pH 3.5-4.5, which mechanism in \na healthy female of reproductive age prevents urogeni-\ntal infections [2-4].\nPostmenopausal decline in the estrogen level leads \nto impairment of blood flow in the lower genitourinary \ntract, decrease in vaginal discharge as well as deteriora-\ntion of connective tissue metabolism which negatively \ninfluences vaginal elasticity. The vaginal exam reveals \nsmooth, pale, thinned mucosa prone to injuries and \nbleeding with minimal trauma. Lack of maturation of \nepithelial cells and thinning of the superficial layer rich \nin glycogen disturbs the normal vaginal microflora. \nThe loss of Lactobacilli suppresses production of lac-\ntic acid which results in the increase in vaginal pH and \ndevelopment of abnormal microflora. In consequence, \nincreased susceptibility to infections with bacteria mi-\ngrating from the vulvar and perianal region is observed. \nClinical symptoms constellation connected with post-\nmenopausal decreased estrogenization of vulvovaginal \nmucosa may be described as atrophic vaginitis, vaginal \natrophy or urogenital atrophy. \nDiagnosis of atrophic vaginitis\nThe most common complaints and symptoms in pa-\ntients with atrophic vaginitis according to Lynch et al. \nare [3]:\n• vaginal dryness (in 3-5% of females of reproductive \nage and in 30-50% of postmenopausal women),\n• vulvovaginal irritation: pruritus, burning; redness and \npetechiae in the case of accompanying inflammation,\n• dyspareunia: pain and burning on sexual intercourse,\n• yellow or purulent discharge,\n• malodor, which is a bacterial vaginosis (BV) symp-\ntom. The development of BV is caused by the decre-\nase in Lactobacilli and colonisation of the lower ge-\nnitourinary tract by anaerobes: Gardnerella vaginalis, \nPrevotella spp., Mobiluncus spp., Atopobium vaginae.\nThe above-mentioned symptoms may be accompa-\nnied by lower urinary tract complaints. Atrophic changes \nof structures derived from embryonic urogenital sinus \nresult in dysuric symptoms, bladder overactivity, stress \nincontinence and recurrent urinary tract infections. \nClinical findings include sparse pubic hair, atrophy \nof labia majora and minora, narrowing of vaginal in-\ntroitus and decrease in length and width of the vagina. \nOther symptoms include decreased or abnormal vaginal \ndischarge, thinning and paleness of vaginal epithelium, \nsmoothing and reduced elasticity of the vulvovaginal \nmucosa, rectocele, uterine prolapse, reddened inflamed \nvulvar skin with fissures. \nLaboratory tests reveal a low serum estradiol level \n(< 30 pg/l) and cytological smear shows a lower percent-\nage of superficial cells with the dominance of parabasal \ncells. Objective tests evaluating the effect of estrogen \non vaginal tissue are: vaginal pH measurement and cell \nmaturation index assessed in smear taken from the lat-\neral vaginal wall. Vaginal pH > 4.6 with no signs of BV \nindicates vaginal atrophy. Vaginal maturation index \nevaluates the percentage of superficial, intermediate \nand parabasal epithelial cell types. In premenopausal \nwomen, there is over 15% of superficial cells, whereas \nin postmenopause the percentage is less than 5%. In \nclinical practice, the vaginal maturation index is rarely \nperformed, mainly because of lack of necessary labora-\ntory devices and experienced staff [2]. Microbiological \nevaluation of vaginal discharge often reveals presence \nof bacterial infection [5, 6].\nAtrophic vaginitis is more commonly encountered in \nobese and diabetic females. It should be noted that loss \nof endogenous estrogen production may result from \nimmunologic disorders, radio- and chemotherapy as \nwell as surgical castration. Besides, low estrogen levels \nare encountered typically in the postpartum and breast-\nfeeding period as well as in the case of pharmacological \ntherapy of endometriosis and uterine fibroids [7].\nAtrophic vaginitis is a chronic condition and symp-\ntoms worsen with time since menopause. It leads to de-\n\nPrzegl¥d menoP auzalny 5/2013\n436\nterioration of quality of life resulting from physical dis-\ncomfort, sexual disorders and severe emotional distress. \nTreatment options\nNon-hormonal preparations\nIn females who choose the non-hormonal treatment \noption or have contraindications to estrogen use, vagi-\nnal moisturizers and lubricants are helpful in sympto-\nmatic atrophic vaginitis. They relieve vaginal symptoms \nsuch as itching and irritation by means of restoring vag-\ninal pH and moisture. They allow for regular sexual ac-\ntivity which maintains proper elasticity and pliability of \nthe vagina. There are also reports on vaginal moisture \nimprovement with use of vitamin E or D preparations. \nSystemic hormone therapy \nExogenous estrogen used in systemic HT restores \nvaginal epithelium and vascularization, improves its \nmoistness and sinks pH level. According to published \nreports, it relieves vaginal symptoms in 75% of wom-\nen with atrophic vaginitis. It was noted that hormonal \ntherapy with an addition of topical estrogen improves \nvaginal symptoms more efficiently than HT itself [1]. \nSystemic hormone therapy is not recommended in fe-\nmales with isolated vaginal symptoms.\nLocal estrogen therapy [8]\nIn the absence of systemic menopausal complaints, \nlocal estrogen therapy is a preferable and efficacious \nmethod of chronic atrophic vaginitis treatment.\nVaginal symptoms quickly resolve on local estrogen \ntherapy. The superficial epithelium layer thickens, vagi-\nnal blood flow improves and so does vaginal pH. Similar \nprocesses are observed in the lower urinary tract. Inter-\nnational societies published EBM guidelines suggesting \nthat in females with urogenital atrophy without con-\ntraindications to estrogen use, the local therapy with \nlow dose estrogen is a treatment of choice. Tissues of \nthe lower genitourinary tract are highly responsive to \nthe pro-proliferative effect of low dose estrogen prep-\narations because of greater, in comparison to uterus, \nsensitivity of estrogen receptors. Typically, no systemic \neffects of local estrogen therapy are observed. \nPreparations used in local estrogen therapy are \navailable in several forms (tablets, pessaries, cream, \nvaginal rings) containing conjugated estrogens, estra-\ndiol, estriol or estrone. Local estrogen therapy effect \nis observed after 4-6 weeks in 80-90% of patients. \nThe treatment is well tolerated even in the case of pro-\nlonged use, although there are sparse data on safety of \nlong-term therapy [9].\nAvailable preparations in topical estrogen therapy:\n• vaginal rings: placed vaginally every 3 months, deliv-\nering 17β-estradiol or estradiol acetate. Not available \nin Poland,\n• vaginal estrogen tablets: containing 25 µg of 17β-estradiol \nor 0.5 mg of estriol.\nAccording to published data, they not only relieve vag-\ninal atrophy but also improve vasomotor symptoms. \n• Conjugated estrogens (CEE) vaginal creams contain \n0.3-0.625 mg of conjugated estrogens: estrone and \n17β-estradiol in a single dose. Highest systemic ab-\nsorption of those preparations, with a higher estra-\ndiol and lower FSH serum level, was observed. There \nwere cases of endometrial proliferation and uterine \nbleeding on CEE therapy, so it is less acceptable in \nvaginal atrophy treatment.\n• Preparations of estriol with Lactobacillus cultures.\nAccording to the majority of international societies, \nestriol is the most preferable and effective estrogen in \nvaginal symptoms treatment. It is produced in the liver \nas 17β-estradiol metabolite and has relatively low sys-\ntemic estrogenic activity. However, it exerts a specific \ncytotropic effect on tissues developing from embryonic \ngenitourinary sinus. As estriol derives from estradiol \nand estrone metabolism, therapy with this hormone \ndoes not affect serum estradiol and estrone levels. Ex-\ncretion of estriol occurs via urine in inactive forms of \nglucuronates and sulphates. Especially favorable out-\ncomes of atrophic vaginitis treatment are observed with \nthe use of estriol combined with Lactobacilli cultures. \nLactobacilli, prevailing in healthy vaginal microflora, \nhave a significant impact on vaginal ecosystem through \nlactic acid and H\n2O2 production. Estriol with Lactoba-\ncilli combination optimizes immunologic mechanisms \nresponsible for detection and fighting infections of \nthe urogenital tract. Mucosal secretion of secretoglobin \n1D and 2A increases thanks to higher activity of respec-\ntive genes transcription. Similarly, the rise of lactofer -\nrin gene activity is observed. Lactoferrin is a protein \nplaying an important role in regulation of immunologic \nresponse of mucosae to bacterial infection. Another fa-\nvorable mechanism is activation of interleukin-1 gene. \nInterleukin-1 regulates immunologic response in vaginal \nmucosa (leukocyte migration, gene expression, inflam-\nmation) that inhibits pathogenic bacteria proliferation. \nLactobacilli in vaginal milieu, in the presence of estriol, \nreinitiate their metabolism and lower vaginal pH within \nfew hours. It leads to quick re-establishment of normal \nvaginal milieu and recline of abnormal microflora symp-\ntoms (most frequently bacterial vaginosis).\nEstriol administered in the ultra-low dose prevents \na typical side effect of estrogen therapy such as en-\ndometrial proliferation. Numerous studies proved that \nthe ultra-low dose of estriol (0.03 mg) combined with \nLactobacilli administered vaginally relieved vaginal at-\nrophy symptoms and re-established normal vaginal \n\nPrzegl¥d menoP auzalny 5/2013\n437\nmicroflora with the same efficacy as 0.05 mg of estra-\ndiol. At the same time, there are no reports of endo-\nmetrial proliferation or increased risk of endometrial \nhyperplasia. The expected effect is achieved in 80-90% \nof females after 3 weeks’ therapy, in some cases after \n4-6 weeks. To maintain the effect of treatment and \navoid frequent recurrence, typically in 6 months after \ntermination of therapy, it is suggested to administer \na maintenance dose 1-2 times a week [10-12].\nLocal therapy was also proven effective in overac-\ntive bladder in postmenopausal women and after uro-\ngynecological incontinence surgeries. The treatment \nis recommended for urogynecological complaints, al-\nthough not only estrogen deficiency is responsible for \ntheir occurrence. It has a favourable effect in women \nwith recurrent urinary tract infections after meno-\npause. In the Cochrane meta-analysis published in \n2008 (9 clinical studies including 3345 women), it was \ndemonstrated that vaginal therapy with estriol decreas-\nes frequency of lower urinary tract infections more ef-\nficiently than oral estrogen therapy. Better outcomes \nof surgical incontinence/prolapse treatment have been \nreported by many authors after local vaginal estrogen \ntherapy [5, 6, 13].\nThe Polish Menopause and Andropause Society in \n2011 published recommendations on local estrogen \ntherapy in postmenopausal women, listing indications \nto therapy [14]:\n• dyspareunia resulting from vaginal dryness,\n• urge incontinence in patients with vaginal atrophy,\n• perioperative therapy in patients undergoing surgery \nbecause of genital prolapse, \n• additional therapy to pelvic floor exercises.\nThe safety of local estrogen therapy\nLocal estrogen therapy led for 12-24 months is rela-\ntively safe. It is believed that it does not require endo-\nmetrial protection by addition of gestagens. The pos-\nsibility of overdose leading to systemic side effects \nand endometrial proliferation and hyperplasia should \nnevertheless be remembered. Currently, the exact in-\nfluence of local estrogen therapy on development or \nrecurrence of breast cancer is not known. There are \nstudy results suggesting that estriol administered in \nhigh doses may stimulate estrogen receptors in breast \nand endometrial tissue. So far there are no guidelines \nregarding duration of local estrogen therapy and ultra-\nlow dose of estrogen is recommended. There are only \nsparse data regarding safety of local estrogen therapy \nin atrophic vaginitis in females with endometrial cancer \nand therefore use of topical estrogens is advisable only \nin individual cases after weighing up risks and benefits \nof the therapy and after consultation with the oncolo-\ngists [1, 13, 15].\nConclusions\nLocal estrogen therapy of atrophic vaginitis is a sim-\nple and safe treatment leading to improvement of \nthe quality of life. The treatment should be commenced \nearly, before irreversible atrophic changes develop. Early \nlocal therapy may prevent urogynecological complaints \noccurrence. It should be continued as maintenance \ntherapy in order to maintain healthy vaginal ecosys-\ntem. Release of symptoms may be achieved by means \nof vaginal moisturizers and lubricants. Recently there \nhave been trials analyzing use of progestagens, andro-\ngens (dehydroepiandrosterone – DHAES) and agonists \nand antagonists of estrogen receptors [16].\nThe authors declare no conflict of interests.\nReferences\n1. Sturdee DW, Panay N; International Menopause Society Writing Group. \nRecommendations for the management of postmenopausal vaginal at-\nrophy. Climacteric 2010; 13: 509-22.\n2. Mac Bride MB, Rhodes DJ, Shuster LT. Vulvovaginal atrophy. Mayo Clin \nProc 2010; 85: 87-94.\n3. Lynch C. Vaginal estrogen therapy for the treatment of atrophic vagini-\ntis. J Womens Health 2010; 8: 1595-606.\n4. Aroutcheva A, Gariti D, Simon M, et al. Defense factors of vaginal lacto-\nbacilli. Am J Obstet Gynecol 2001; 185: 375-9.\n5. Stachowiak G, Pertyński T. Kliniczne aspekty atrofii urogenitalnej u ko-\nbiet. Przegl Menopauz 2011; 15: 1-4.\n6. Wilamowska A, Woźniak P, Stetkiewicz T, et al. Biocenoza pochwy u ko-\nbiet po menopauzie. Przegl Menopauz 2011; 15: 469-72.\n7. Tomaszewski J. Estrogenoterapia dopochwowa – czy tylko dla kobiet po \nmenopauzie? Przegl Menopauz 2008; 12: 158-67.\n8. Hohenhaus MH. Vulvovaginal atrophy: a common – and commonly \noverlooked – problem. Med Health R I 2011; 94: 138-40.\n9. Jaisamrarn U, Triratanachat S, Chaikittisilpa S, et al. Ultra-low-dose es-\ntriol and lactobacilli in the local treatment of postmenopausal vaginal \natrophy. Climacteric 2013; 16: 1-9.\n10. Griessera H, Skonietzki S, Fischer T, et al. Low dose estriol pessaries for \nthe treatment of vaginal atrophy: A double-blind placebo-controlled trial \ninvestigating the efficacy of pessaries containing 0.2 mg and 0.03 mg \nestriol. Maturitas 2012; 71: 360-8.\n11. Buhling KJ, Eydeler U, Borregaard S, et al. Systemic bioavailability of \nestriol following single and repeated vaginal administration of 0.03 mg \nestriol containing pessaries. Arzneimittelforschung 2012; 62: 378-83.\n12. The North American Menopause Society. The 2012 hormone therapy \nposition statement of the North American Menopause Society. Meno-\npause 2012; 19: 257-71.\n13. Kokot-Kierepa M, Bartuzi A, Kulik-Rechberger B, et al. Lokalna terapia \nestrogenowa – implikacje kliniczne – 2012 update. Ginekol Pol 2012; \n83: 772-3.\n14. Rekomendacje Polskiego Towarzystwa Menopauzy i Andropauzy \ndotyczące stosowania lokalnej terapii hormonalnej u kobiet w okresie \nmenopauzy. Przegl Menopauz 2011; 15: 263-6.\n15. Neven P, Donders G, Mogele M, et al. Ultra-low dose vaginal estriol and \nLactobacillus acidophilus (Gynoflor®) in early breast cancer survivors \non aromatase inhibitors: Pharmacokinetic, efficacy and safety results \nfrom a phase I study. Cancer Res 2012; 72 Suppl. 3: 2.\n16. Panjari M, Davis SR. Vaginal DHEA to treat menopause related atrophy: \nA review of the evidence. Maturitas 2011; 70: 22-5.","source_license":"CC0","license_restricted":false}