Signs Of Vaginal Atrophy Research Articles

Does age at the start of treatment for vaginal atrophy predict response to vaginal estrogen therapy? Post hoc analysis of data from a randomized clinical trial involving 205 women treated with 10 μg estradiol vaginal tablets.

Local estrogen therapy (ET) can improve vaginal atrophy symptoms and associated cellular changes in postmenopausal women. This study evaluated whether age at the start of treatment influences response. This post hoc analysis used data from a double-blind, randomized, placebo-controlled trial (NCT00108849), which treated 205 postmenopausal women aged ≥45 years with 10 μg vaginal ET for 52 weeks.Women aged <60 or ≥60 years at treatment start were evaluated according to the following: vaginal maturation index (assessed by vaginal cytology samples), vaginal pH, and most bothersome symptom (both graded on four-point scales). Covariance analysis aimed to evaluate mean change differences between groups from baseline-week 52. Vaginal ET improved vaginal maturation index (for all cell layers), vaginal pH, and symptom scores for both age groups. However, cytological profiles were significantly different in the <60 (n = 143) versus ≥60 years group (n = 55, estimated effect: -3.7, P = 0.0003 [parabasal cells]; 5.8, P = 0.0002 [intermediate cells]), indicating reduced cellular responsiveness to treatment among older women. Treatment effect on vaginal pH was less for older women, with a between-group difference of -0.19 (standard error = 0.05; P = 0.0003). Findings suggest that treatment may be initiated at any age since low-dose vaginal ET improved symptoms and signs of vaginal atrophy in both younger (<60 years) and older (≥60 y) women. The stronger response observed in younger women supports current clinical recommendations to start treatment early. Continued treatment may be important to avoid recurrence of vaginal atrophy.

Effectiveness of hormones in postmenopausal pelvic floor dysfunction\u2014International Urogynecological Association research and development\u2014committee opinion

Introduction and hypothesisThere is clear evidence of the presence of estradiol receptors (ERs) in the female lower urinary and genital tract. Furthermore, it is a fact that estrogen deficiency after menopause may cause atrophic changes of the urogenital tract as well as various urinary symptoms. Moreover, the effect of hormone replacement therapy (HRT) on urinary incontinence (UI) symptoms as well as pelvic organ prolapse (POP), anal incontinence (AI) and vulvovaginal symptoms (VVS) is still a matter of debate. This committee opinion paper summarizes the best evidence on influence of sex steroids as well as hormonal treatment (local and systemic) in postmenopausal women with pelvic floor disorders.MethodsA working subcommittee from the International Urogynecology Association (IUGA) Research and Development Committee was formed. A thorough literature search was conducted and an opinion statement expressed. The literature regarding hormones and pelvic floor disorders was reviewed independently and summarized by the individual members of the sub-committee.ResultsThe majority of studies reported that vaginal estrogen treatment when compared with placebo has more beneficial effects on symptoms and signs of vaginal atrophy including sensation of burning, dyspareunia and UI symptoms. Definitive evidence on local estrogen application and prolapse treatment or prevention is lacking. A statistically significant increase in risk of worsening of UI as well as development of de novo incontinence was observed with estrogen-only or combination systemic HRT.ConclusionsIn summary, local estrogen seems to be safe and effective in the treatment of VVS and can also improve urinary symptoms in postmenopausal patients with UI, but most of these recommendations correspond to evidence level 2C. The evidence in POP is still scarce but not in favor of benefit. Finally, the duration of local estrogen treatment (LET), optimal dosage, long-term effects and cost-effectiveness compared with current practice are still unknown.

Effect of a gel containing pilocarpine on vaginal atrophy in castrated rats

OBJECTIVES:To evaluate the effect of Carbopol gel formulations containing pilocarpine on the morphology and morphometry of the vaginal epithelium of castrated rats.METHODS:Thirty-one female Wistar-Hannover rats were randomly divided into four groups: the control Groups I (n=7, rats in persistent estrus; positive controls) and II (n=7, castrated rats, negative controls) and the experimental Groups, III (n=8) and IV (n=9). Persistent estrus (Group I) was achieved with a subcutaneous injection of testosterone propionate on the second postnatal day. At 90 days postnatal, rats in Groups II, III and IV were castrated and treated vaginally for 14 days with Carbopol gel (vehicle alone) or Carbopol gel containing 5% and 15% pilocarpine, respectively. Next, all of the animals were euthanized and their vaginas were removed for histological evaluation. A non-parametric test with a weighted linear regression model was used for data analysis (p<0.05).RESULTS:The morphological evaluation showed maturation of the vaginal epithelium with keratinization in Group I, whereas signs of vaginal atrophy were present in the rats of the other groups. Morphometric examinations showed mean thickness values of the vaginal epithelium of 195.10±12.23 μm, 30.90±1.14 μm, 28.16±2.98 μm and 29.84±2.30 μm in Groups I, II, III and IV, respectively, with statistically significant differences between Group I and the other three groups (p<0.0001) and no differences between Groups II, III and IV (p=0.0809).CONCLUSION:Topical gel formulations containing pilocarpine had no effect on atrophy of the vaginal epithelium in the castrated female rats.

Unmet needs in VVA

Vulvo-vaginal atrophy, also called atrophic vaginitis, is a chronic, progressive condition that results from the decrease in oestrogen levels in the vagina that commonly occurs after the menopause. Symptoms include vaginal dryness, dyspareunia, vulval and vaginal irritation and itching, soreness, vaginal discharge, post-coital bleeding, etc. [ [1] MacBride M.B. Rhodes D.J. Shuster L.T. Vulvovaginal atrophy. Mayo Clin Proc. 2010; 85: 87-94 Abstract Full Text Full Text PDF PubMed Scopus (334) Google Scholar ]. It is estimated that between 69% [ [2] Gass M.L.S. Cochrane B.B. Larson J.C. et al. Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women's Health Initiative. Menopause. 2011; 18: 1160-1171 Crossref PubMed Scopus (67) Google Scholar ] and 98% [ [3] Freedman M.A. Vaginal pH, estrogen and genital atrophy. Menopause Manage. 2009; 17: 9-13 Google Scholar ] of postmenopausal women have signs of vaginal atrophy, with worsening features with increasing age after the menopause. In cross sectional surveys, around 50% of postmenopausal women complain of symptoms of vaginal discomfort attributable to VVA [ [4] Nappi R.E. Palacios S. Impact of vulvovaginal atrophy on sexual health and quality of life at postmenopause. Climacteric. 2014; 17: 3-9 Crossref PubMed Scopus (170) Google Scholar ]. VVA has a significant impact on the personal and sexual lives of women and their partners. Vaginal discomfort had a negative impact on many aspects of women's self-esteem and emotional well-being [ [5] Nappi R.E. Mattsson L.Å. Lachowsky M. Maamari R. Giraldi A. The CLOSER survey: impact of postmenopausal vaginal discomfort on relationships between women and their partners in Northern and Southern Europe. Maturitas. 2013; 75: 373-379 Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar ]. 75% of postmenopausal women surveyed admitted it had a negative impact on quality of life [ [6] Nappi R.E. Kokot-Kierepa M. Vaginal Health: Insights, Views & Attitudes (VIVA) – results from an international survey. Climacteric. 2012; 15: 36-44 Crossref PubMed Scopus (254) Google Scholar ] and relationships with more than 70% of men noting that their partner avoided sexual intimacy because of vaginal discomfort. Despite the impact on quality of life and relationships, the fact that 62% of women complain of moderate or severe symptoms and 55% had the symptoms for 3 or more years, vulvar and vaginal atrophy remain an underreported, underdiagnosed and therefore also an undertreated condition [ [7] Parish S.J. Nappi R.E. Krychman M.L. et al. Impact of vulvovaginal health on postmenopausal women: a review of surveys on symptoms of vulvovaginal atrophy. Int J Womens Health. 2013; 5: 437-447 Crossref PubMed Scopus (141) Google Scholar ] for a number of different reasons.

Local Oestrogen for Pelvic Floor Disorders: A Systematic Review.

ObjectiveThe decline in available oestrogen after menopause is a possible etiological factor in pelvic floor disorders like vaginal atrophy (VA), urinary incontinence (UI), overactive bladder (OAB) and pelvic organ prolapse (POP). This systematic review will examine the evidence for local oestrogen therapy in the treatment of these pelvic floor disorders.Evidence AcquisitionWe performed a systematic search in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the non-MEDLINE subset of PubMed from inception to May 2014. We searched for local oestrogens and VA (I), UI/OAB (II) and POP (III). Part I was combined with broad methodological filters for randomized controlled trials (RCTs) and secondary evidence. For part I and II two reviewers independently selected RCTs evaluating the effect of topical oestrogens on symptoms and signs of VA and UI/OAB. In part III all studies of topical oestrogen therapy in the treatment of POP were selected. Data extraction and the assessment of risk of bias using the Cochrane Risk of Bias Tool was undertaken independently by two reviewers.Evidence SynthesisThe included studies varied in ways of topical application, types of oestrogen, dosage and treatment durations. Objective and subjective outcomes were assessed by a variety of measures. Overall, subjective and urodynamic outcomes, vaginal maturation and vaginal pH changed in favor of vaginal oestrogens compared to placebo. No obvious differences between different application methods were revealed. Low doses already seemed to have a beneficial effect. Studies evaluating the effect of topical oestrogen in women with POP are scarce and mainly assessed symptoms and signs associated with VA instead of POP symptoms.ConclusionTopical oestrogen administration is effective for the treatment of VA and seems to decrease complaints of OAB and UI. The potential for local oestrogens in the prevention as well as treatment of POP needs further research.

The therapeutic effect of a new ultra low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of postmenopausal vaginal atrophy

The aim of this study was to evaluate the efficacy and safety of a new low-concentration estriol formulation (0.005% estriol vaginal gel), providing an ultra low dose of estriol per application (50 μg), for the local treatment of postmenopausal vaginal atrophy. Postmenopausal women with symptoms and signs of vaginal atrophy were enrolled in a prospective, double-blind, placebo-controlled study. Women received either 1 g of vaginal gel containing 50 μg of estriol or placebo gel, daily for 3 weeks and then twice weekly up to 12 weeks. A cytological vaginal study, evaluation of vaginal pH, and assessment of symptoms and signs of vaginal atrophy were performed, and changes between baseline and weeks 3 and 12 were assessed. Adverse events were recorded. A total of 167 women were included (114 received estriol and 53 received placebo). After 12 weeks of therapy, a superiority of estriol compared with placebo gel was shown in the change in maturation value and vaginal pH (P < 0.001 and P < 0.001, respectively). The superiority of estriol was well demonstrated in improvement of vaginal dryness (P = 0.001) and the Global Symptom Score (P = 0.018). Estriol gel proved also superior in the improvement of several of the most outstanding vaginal signs of vaginal atrophy evaluated. After 3 weeks, estriol gel also showed a superiority over the placebo gel in most symptoms and signs evaluated. Treatment-related adverse events were similar among groups. 0.005% Estriol vaginal gel, a new formulation providing an ultra low dose of estriol per application, was shown to be safe and effective in the treatment of postmenopausal vaginal atrophy.

Intravaginal DHEA, by a strictly local action, exerts beneficial effects on both vaginal atrophy symptoms and sexual dysfunction.

Following complete cessation of estrogen secretion by the ovaries at menopause, all estrogens and practically all androgens are made from dehydroepiandro-sterone (DHEA) of adrenal/ovarian origin. Although being an inactive molecule itself, DHEA is transformed at various levels and ratios into estrogens and/or androgens only in the tissues that possess the required cell-specific steroidogenic enzymes with minimal or no release of the active hormones in the blood according to the mechanisms of intracrinology. Vaginal atrophy affects 50% of postmenopausal women from 50 to 60years of age and 72% of women 70years and older. At the standard 12-week time interval, 0.5% DHEA caused a 45.9±5.31 (p<0.0001 vs. placebo) decrease in the percentage of parabasal cells, a 6.8%±1.29% (p<0.0001 vs. placebo) increase in superficial cells, a 1.3±0.13 unit (p<0.0001 vs. placebo) decrease in vaginal pH and a 1.5±0.14 score unit (p<0.0001 vs. placebo) decrease in the severity of the most bothersome symptom. Similar changes were observed on vaginal secretions, color, epithelial surface thickness and epithelial integrity. In addition to the effects of intravaginal DHEA on the symptoms and signs of vaginal atrophy, a time- and dose-dependent improvement in the four domains of sexual function was observed, namely desire, arousal, orgasm and pain at sexual intercourse. The present data indicate that combined androgenic/estrogenic stimulation in the three layers of the vagina exerts important beneficial effects on sexual function in women without systemic action on the brain and other extravaginal tissues.

Intravaginal dehydroepiandrosterone (Prasterone), a physiological and highly efficient treatment of vaginal atrophy

Because the secretion of dehydroepiandrosterone (DHEA), the exclusive source of sex steroids in postmenopausal women, is already decreased by 60% and continues to decline at the time of menopause, the objective of this study was to examine the effect of intravaginal DHEA on the symptoms and signs of vaginal atrophy. This prospective, randomized, double-blind and placebo-controlled phase III clinical trial studied the effect of Prasterone (DHEA) applied locally in the vagina on the signs and symptoms of vaginal atrophy in 216 postmenopausal women. All three doses (0.25%, 0.5%, and 1.0%) of DHEA ovules applied daily intravaginally induced a highly significant beneficial change in the percentage of vaginal parabasal and superficial cells and pH as well as in the most bothersome symptom at 2 weeks. At the standard 12-week time interval, 0.5% DHEA caused a 45.9 +/- 5.31 (P < 0.0001 vs placebo) decrease in the percentage of parabasal cells, a 6.8 +/- 1.29% (P < 0.0001) increase in superficial cells, a 1.3 +/- 0.13 unit (P < 0.0001) decrease in vaginal pH, and a 1.5 +/- 0.14 score unit (P < 0.0001) decrease in the severity of the most bothersome symptom. Similar changes were seen on vaginal secretions, color, epithelial surface thickness, and epithelial integrity. Comparable effects were observed at the 0.25% and 1.0% DHEA doses. Local Prasterone, through local androgen and estrogen formation, causes a rapid and efficient reversal of all the symptoms and signs of vaginal atrophy with no or minimal changes in serum steroids, which remain well within the normal postmenopausal range. This approach avoids the fear of systemic effects common to all presently available estrogen formulations and adds a novel physiological androgenic component to therapy.

Efficacy of a new, oral estradiol acetate formulation for relief of menopause symptoms

To determine the efficacy of three doses of a new, oral formulation of estradiol acetate (EA) for alleviation of vasomotor and urogenital symptoms in postmenopausal women. Two separate 12-week studies were undertaken in postmenopausal women with moderate to severe vasomotor symptoms. In the first study, women were randomly assigned to EA 0.9 mg/day, EA 1.8 mg/day, or placebo (study 1; N = 293), and in the second study to oral EA 0.45 mg/day or placebo (study 2; N = 259). Women recorded the frequency and severity of vasomotor symptoms daily and urogenital symptoms weekly on diary cards. Investigators assessed signs of vaginal atrophy. Frequency of moderate to severe vasomotor symptoms decreased significantly versus placebo, starting at week 2 in the EA 1.8-mg group (P = 0.005), week 3 in the EA 0.9-mg group (P = 0.003), and week 6 in the EA 0.45-mg group (P < 0.05). At week 12, mean percent reduction from baseline in vasomotor-symptom frequency was 91%, 78%, and 61%, respectively. Vasomotor-symptom severity decreased significantly versus placebo, starting at weeks 2 and 3 with EA 1.8 mg and 0.9 mg, respectively, and at week 5 with EA 0.45 mg. Vaginal pH and maturation index improved significantly in all EA groups versus placebo, and some signs and symptoms of vaginal atrophy improved at the EA 0.9- and 1.8-mg doses. Side effects were mild to moderate and consistent with estrogen therapy. Oral EA at all doses was well tolerated and significantly reduced the frequency and severity of postmenopause symptoms versus placebo.

The outcome of pelvic examinations in women 40-60 years of age with lower urinary tract symptoms

We set out to assess the outcome of pelvic examination in women 40-60 years of age with one or more lower urinary tract symptoms. This was an ongoing longitudinal cohort study set in one rural and one urban county in Denmark. One hundred and ninety-six women with one or more lower urinary tract symptoms occurring at least weekly were selected at random. Ages ranged from 40 to 60 years. Pelvic findings involving genital prolapse, signs of vaginal atrophy, and pelvic mass as well as a history of hormonal status and estrogen deficiency symptoms were documented and assessed. One hundred and six women (54.1%) were recruited. First degree cystocele, rectocele, and uterine prolapse occurred in 24 (22.6%), seven (6.6%), and six (5.7%), women respectively. No significant association between first-degree genital prolapse and subtypes of lower urinary tract symptoms (LUTS) was observed. The number of women with second or third degree cystocele, rectocele, and uterine prolapse was three (2.8%), two (1.9%), and two (1.9%), respectively. The positive predictive vaginal findings in each subtype of LUTS indicating an oestrogen deficiency were in the interval 72.0- 90.0 while the negative predictive vaginal findings were in the interval 24.7-27.6%, respectively. In six women (5.7%) a leiomyoma was observed. In one woman the size of the uterus exceeded the size of a 12-week pregnancy. Genital prolapse more than first degree and pelvic masses were infrequent findings among women with LUTS. Signs of vaginal atrophy associated poorly with a history of hormonal depletion and symptoms indicating oestrogen deficiency. However even an infrequent pathologic finding is significant. Therefore we still recommend pelvic examinations in all women with LUTS.

Continuous low dose estradiol released from a vaginal ring versus estriol vaginal cream for urogenital atrophy

Objectives: To determine if the efficacy of continuous low dose estradiol released from a vaginal ring is equivalent to estriol vaginal cream regarding improvement of the patient's subjective feeling of vaginal dryness and to determine if there is a preference for either of the two study treatments. Methods: Open-label randomized parallel group trial with active control with a blind evaluation of vaginal cytology and with a cross-over (change-over) phase for preference comparison. One hundred and sixty five postmenopausal women with symptoms of vaginal dryness and signs of vaginal atrophy were randomized to an estradiol ring (Estring ®) or estriol cream (Synapause ®). The duration of each treatment period was 12 weeks. Results: Both study treatments were equally effective regarding the ability to alleviate the symptom feeling of vaginal dryness and the signs of vaginal atrophy. Both treatments were efficient in restoring the vaginal mucosa, recorded as higher maturation values and as decreased vaginal pH. Estring was superior to estriol cream regarding preference of treatment. Both treatments were equivalent for the occurrence of adverse events, including bleeding. Conclusion: data from this change-over study confirm efficacy and safety of both the vaginal ring and cream in the treatment of postmenopausal women with urogenital atrophy symptoms and signs. The patients had a strong preference for the vaginal ring.