Aloe Vera; A new treatment for atrophic vaginitis, A randomized double-blinded controlled trial.

AIM OF THE STUDY: Vaginal atrophy is of the most common problems during menopause with significant psychosocial and medical consequences. Estrogen as an approved therapy for vaginal atrophy can be associated with adverse effects and several contraindications in menopause patients. The aim is to compare the effect of Aloe Vera vaginal cream with commercially available estrogen vaginal cream for management of vaginal atrophy in menopause females. MATERIALS AND METHODS: This is a double-blinded randomized controlled trial on 60menopause female with complaints of vaginal atrophy symptoms. Subjects were randomly allocated in two groups of 30 patients, named as estrogen and Aloe Vera groups. Vaginal health index (VHI), maturity value (MV), vaginal cytologic smear, transvaginal sonography (TVS) and severity of symptoms related to vaginal atrophy were assessed before and after 6-weeks of vaginal cream administration. RESULTS: Comparison of MV before and after treatment revealed that superficial cells were significantly increased after administration of both vaginal cream (6.67 VS 54.33 in Aloe Vera group; 4.33 VS 59.67 in estrogen group). In addition, VHI (13.83 vs 20.13 in Aloe Vera group; 13.97 vs 19.93 in estrogen group) and symptoms of vaginal atrophy (3.63 vs 1.10 in Aloe Vera group; 3.90 vs 0.66 in estrogen groups) were also significantly improved after treatment in both groups. There was no significant difference between groups after treatment except for fluid volume with a superiority in Aloe Vera group (P-value = 0.004) CONCLUSION: Aloe Vera vaginal cream can be as effective as estrogen vaginal cream in the management of vaginal atrophy in menopause females.

Comparison of the Effects of Fenugreek Vaginal Cream and Ultra Low- Dose Estrogen on Atrophic Vaginitis.

INTRODUCTION: Atrophic vaginitis is a common problem in postmenopausal women and results from decreased levels of blood estrogen. It is associated with symptoms of itching, burning, dyspareunia, and postmenopausal bleeding. The present study evaluated the effects of fenugreek extract on atrophic vaginitis. MATERIALS AND METHODS: This randomized controlled clinical trial was performed on 60 postmenopausal women in Ardabil, Iran, in 2018. The participants were selected using block randomization with the allocation ratio 1:1. Those in the intervention group received 0.5g (the applicator filled to the half-full mark) fenugreek vaginal cream 5% twice a week for 12 weeks. The control group received conjugated estrogens vaginal cream at the dose of 0.625 mg (the applicator filled to the half-full mark) containing 0.3 mg of conjugated estrogens. Atrophic vaginitis was evaluated before and after the treatment through clinical examination, clinical signs, and measurement of Vaginal Maturation Index (VMI). FINDINGS: After the 12-week intervention and modification of the baseline score, the mean (standard error) score for atrophic vaginitis signs was 3.100 (1.43-4.75). This difference was statistically significant in intragroup comparison and in favor of the control group in intergroup comparison (p=0.001). VMI was less than 49% in 86.7% and 46.7% of the participants in the intervention and control groups, respectively. This was a significant difference in favor of the control group (p=0.001). CONCLUSION: The results of this study showed that total fenugreek extract could be effective in treating signs of atrophic vaginitis, but it was not as effective as ultra-low-dose estrogen.

Application of conjugated estrogen cream in the treatment of postmenopausal atrophic vaginitis.

To observe and analyze the effect of conjugated estrogen cream in the treatment of postmenopausal atrophic vaginitis. The 160 patients clearly diagnosed with postmenopausal atrophic vaginitis and treated in our hospital were selected as subjects and divided into study group and reference group with equal number of cases. The reference group was treated with compound metronidazole suppository, while the study group was treated with conjugated estrogen cream. The treatment efficacy of the two groups was compared and observed. Comparison of estradiol and folliclestimulating hormone levels after treatment in the two groups show that the study group has obvious advantage over the reference group, p<0.05; comparison of vagina cleanliness in the two groups after treatment shows the study group is significantly superior to the reference group, p<0.05; comparison of incidence of adverse reactions in the two groups shows that the study group has lower incidence, with statistical significance in comparison between the groups, p<0.05. Treatment of postmenopausal atrophic vaginitis with combination of conjugated estrogen cream and compound metronidazole suppository can achieve good results with high safety and reliability.

17ß-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis.

OBJECTIVES: The efficacy and safety of 25-µg 17ß-estradiol vaginal tablets (Vagifem) were assessed and compared with 1.25-mg conjugated equine estrogen vaginal cream (Premarin Vaginal Cream) for the relief of menopausal-derived atrophic vaginitis, resulting from estrogen deficiency. DESIGN: In a multicenter, open-label, randomized, parallel-group study, 159 menopausal women were treated for 24 weeks with either vaginal tablets or vaginal cream. Efficacy was evaluated by relief of vaginal symptoms and concentrations of serum estradiol and follicle-stimulating hormone. Safety was monitored by the incidence of adverse events, evaluation of endometrial biopsies, and clinical laboratory results. Patients also assessed the acceptability of the study medications. RESULTS: Composite scores of vaginal symptoms (dryness, soreness, and irritation) demonstrated that both treatments provided equivalent relief of the symptoms of atrophic vaginitis. At weeks 2, 12, and 24, increases in serum estradiol concentrations and suppression of follicle-stimulating hormone were observed in significantly more patients who were using the vaginal cream than in those who were using the vaginal tablets (p < 0.001). Fewer patients who were using the vaginal tablets experienced endometrial proliferation or hyperplasia compared with patients who were using the vaginal cream. Significantly more patients who were using the vaginal tablets rated their medication favorably than did patients who were using the vaginal cream (p ≤ 0.001). Patients who were receiving the vaginal tablets also had a lower incidence of patient withdrawal (10% versus 32%). CONCLUSIONS: Treatment regimens with 25-µg 17ß-estradiol vaginal tablets and with 1.25-mg conjugated equine estrogen vaginal cream were equivalent in relieving symptoms of atrophic vaginitis. The vaginal tablets demonstrated a localized effect without appreciable systemic estradiol increases or estrogenic side effects. Vaginal tablet therapy resulted in greater patient acceptance and lower withdrawal rates compared with vaginal cream therapy.

Prevention of recurrent lower urinary tract infections in postmenopausal women with genitourinary syndrome: outcome after 6 months of treatment with ospemifene.

Aim of this study was to evaluate the efficacy of ospemifene in the prevention of recurrent lower urinary tract infections in postmenopausal women with vulvovaginal atrophy. The study have a retrospective design. Thirty-nine patients were enrolled. Patients underwent clinical examination and urine culture. The urinary symptoms and the quality of life were evaluated with UTISA score, PUF and SF-36 questionnaires before and after treatment. All 39 patients received ospemifene 60 mg one tablet/daily for 6 months. Adverse effects and complications were assessed. Thirty-nine patients were enrolled in the study. Two patients experienced one new UTI episode and the mean number of positive urine culture decreased significantly after 6 months (3.65 ± 2.12 vs 0.25 ± 0.17, p < .0001). The mean number of urinary infection symptoms decreased significantly after treatment; dysuria reduced (4.76 ± 2.45 vs 0.89 ± 1.12). PUF score and SF-36 showed a statistically significant change (22.43 ± 5.89 vs 12.14 ± 3.21) and (52.86 ± 9.21 vs 83.43 ± 10.76). No adverse effects were reported and the total success rate was the 92.3% after 6 months at PGI-I. Ospemifene is a valid alternative with excellent tolerability for the UTIS prevention in postmenopausal patients.

Vitamin D Proliferates Vaginal Epithelium through RhoA Expression in Postmenopausal Atrophic Vagina tissue.

Postmenopausal atrophic vagina (PAV) is the thinning of the walls of the vagina and decreased lugae of the vagina. PAV is caused by decreased estrogen levels in postmenopausal women. However, the harmful effects of hormone replacement therapy (HRT) have resulted in considerable caution in its use. Various estrogen agonist treatment options are available. Vitamin D is influences the regulation of differentiation and proliferation of various cells, especially tissues lining stratified squamous epithelium, such as the vaginal epithelium. In this study, we hypothesized that vitamin D could provide an alternative and a safe treatment option for PAV by promoting the proliferation and differentiation of the vaginal epithelium. Thirty six patients were enrolled in this case-control study. Vitamin D associated proteins in a vitamin D and sex hormone treated vaginal epithelial cell line as well as normal and PAV tissues were measured. To confirm of cell-to-cell junction protein expression, cell line and tissue studies included RT-PCR, immunohistochemistry staining, and immunoblot analyses. The expression of cell-to-cell junction proteins was higher in women with symptoms of atrophic vagina tissue compared to women without the symptoms. Vitamin D stimulated the proliferation of the vaginal epithelium by activating p-RhoA and Erzin through the vitamin D receptor (VDR). The results suggest that vitamin D positively regulates cell-to-cell junction by increasing the VDR/p-RhoA/p-Ezrin pathway. This is the first study to verify the relationship of the expression of RhoA and Ezrin proteins in vaginal tissue of PAV.

A Dermatologist's Approach to Genitourinary Syndrome of Menopause.

BACKGROUND: Genitourinary syndrome of menopause (GSM) is a debilitating condition caused by hypoestrogenism that presents with vaginal dryness and dyspareunia as well as other genital, sexual, and urinary symptoms. Previously known as atrophic vaginitis, the term GSM is now used. OBJECTIVE: To help familiarise dermatologists with diagnosing and managing GSM. METHODS: In total, 218 articles were identified and reviewed by 2 independent authors using PubMed. Articles included were from December 2005 to December 2015. Sixty-seven articles met our inclusion criteria. RESULTS: GSM is a clinical diagnosis, requiring the presence of symptoms that should be bothersome and not accounted for by another condition. A pH test may help with diagnosis as vaginal pH will be increased from acidic to neutral. The Papanicolaou test is not recommended because of poor clinical correlation. First-line treatment is low-dose local vaginal estrogen therapy, which has proven efficacy and safety. Serum estrogen levels are not significantly affected with the exception of creams containing high-dose conjugated equine estrogens. Other options have yet to be approved for use in Canada but show promise. CONCLUSION: GSM is a debilitating and common condition that suffers from barriers to diagnosis and treatment. Current treatments are well tolerated, rewarding, and effective with rapid onset.

Efficacy of an orally administered combination of hyaluronic acid, chondroitin sulfate, curcumin and quercetin for the prevention of recurrent urinary tract infections in postmenopausal women.

OBJECTIVE: To assess whether the orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin and quercetin could be effective in preventing recurrent cystitis in postmenopausal women and whether its efficacy was conditioned by the concurrent use of local estrogen therapy. STUDY DESIGN: This was a prospective evaluation of 145 postmenopausal women consecutively recruited from the database of three different investigators. All women should have mild-to-moderate urogenital atrophy and a history of recurrent urinary tract infections (≥2 episodes within 6 months or ≥3 episodes within 12 months documented by positive urine cultures) during the last year. Patients were assigned to three different therapeutic regimens: the first group was treated only with vaginal estrogens, the second group only with HA, CS, curcumin and quercetin per os, and the third group was treated with HA, CS, curcumin and quercetin associated with local estrogens. We evaluated the number of patients with <2 infective episodes in the 6-month follow-up and <3 episodes in the 12-month follow-up (main aim definition) and the reduction of related symptoms through a Visual Analog Scale (VAS) and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. Student's t-test and chi-squared test were used for data analysis as appropriate. RESULTS: At 6-month follow up, the main aim rate was 8%, 11.1% and 25% in the three groups, respectively (p<0.05 compared to baseline only in group 3). Although the reduction in the number of recurrent episodes became significant in all groups at 1 year follow-up, the main aim rate was almost double in women receiving both local estrogens and oral therapy (group 3) compared to those receiving single treatments. The improvement of related symptoms was significant in all groups at 12-month follow-up. CONCLUSIONS: In postmenopausal women, the combination of HA, CS, curcumin and quercetin per os was effective in preventing recurrent urinary tract infections, especially if administered with vaginal estrogen therapy.

Vaginal estrogen products in hormone receptor-positive breast cancer patients on aromatase inhibitor therapy.

Atrophic vaginitis represents a major barrier to compliance with aromatase inhibitor (AI) therapy in breast cancer (BC) survivors. While local estrogen therapy is effective for postmenopausal vaginal dryness, the efficacy of such therapies has not been evaluated systematically in hormone receptor-positive (HR+) BC patients on AI therapy. Furthermore, the potential risk of breast cancer recurrence with vaginal estrogen therapy represents a long-term safety concern for the patients with HR + BC. Unfortunately, there is no standardized assay to measure very low concentrations of estradiol (E2) in these women being treated with AI therapy. This makes it difficult to evaluate even indirectly the potential risk of BC recurrence with vaginal estrogen therapy in HR + BC patients on AI therapy. In this review, we describe available assays to measure very low concentrations of E2, discuss the Food and Drug Administration-approved vaginal estrogen products on the market, and summarize published and ongoing clinical trials evaluating the safety and efficacy of vaginal estrogen in HR + BC patients on AI therapy. In the absence of any randomized controlled clinical trials, this review serves as a summary of available clinical data and ongoing studies to aid clinicians in selecting the best available option for their patients.

Vaginal estrogen for genitourinary syndrome of menopause: a systematic review.

OBJECTIVE: To comprehensively review and critically assess the literature on vaginal estrogen and its alternatives for women with genitourinary syndrome of menopause and to provide clinical practice guidelines. DATA SOURCES: MEDLINE and Cochrane databases were searched from inception to April 2013. We included randomized controlled trials and prospective comparative studies. Interventions and comparators included all commercially available vaginal estrogen products. Placebo, no treatment, systemic estrogen (all routes), and nonhormonal moisturizers and lubricants were included as comparators. METHODS OF STUDY SELECTION: We double-screened 1,805 abstracts, identifying 44 eligible studies. Discrepancies were adjudicated by a third reviewer. Studies were individually and collectively assessed for methodologic quality and strength of evidence. TABULATION, INTEGRATION, AND RESULTS: Studies were extracted for participant, intervention, comparator, and outcomes data, including patient-reported atrophy symptoms (eg, vaginal dryness, dyspareunia, dysuria, urgency, frequency, recurrent urinary tract infection (UTI), and urinary incontinence), objective signs of atrophy, urodynamic measures, endometrial effects, serum estradiol changes, and adverse events. Compared with placebo, vaginal estrogens improved dryness, dyspareunia, urinary urgency, frequency, and stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). Urinary tract infection rates decreased. The various estrogen preparations had similar efficacy and safety; serum estradiol levels remained within postmenopausal norms for all except high-dose conjugated equine estrogen cream. Endometrial hyperplasia and adenocarcinoma were extremely rare among those receiving vaginal estrogen. Comparing vaginal estrogen with nonhormonal moisturizers, patients with two or more symptoms of vulvovaginal atrophy were substantially more improved using vaginal estrogens, but those with one or minor complaints had similar symptom resolution with either estrogen or nonhormonal moisturizer. CONCLUSION: All commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy-related complaints and have additional utility in patients with urinary urgency, frequency or nocturia, SUI and UUI, and recurrent UTIs. Nonhormonal moisturizers are a beneficial alternative for those with few or minor atrophy-related symptoms and in patients at risk for estrogen-related neoplasia. CLINICAL TRIAL REGISTRATION: PROSPERO International prospective register of systematic reviews, http://www.crd.york.ac.uk/PROSPERO/, CRD42013006656.

Treatment of vaginal atrophy.

Vaginal or vulvovaginal atrophy is a widespread but poorly recognized condition of peri- and post-menopausal women. It causes urogenital symptoms of dryness, reduced lubrication, itching, burning, irritable bladder symptoms and painful intercourse. This impacts quality of life and sexual health, but increases with time rather than reduces, as with most other menopausal symptoms. With early identification, treatments can improve these symptoms and reverse the physical changes. However, when embedded, bladder and sexual changes have occurred and these may be more difficult to remedy. Therefore, it is important to educate both healthcare professionals and women about these symptoms and advise on the range of interventions available.

Animal models for the effective development of atrophic vaginitis therapies: possibilities and limitations.

INTRODUCTION: Vaginal atrophy (VA) is an inflammation of the vagina that develops when there is a significant decrease in levels of the estrogen. Prolonged periods of hypoestrogenism may induce severe VA and treatment is essential. This is a significant problem which requires more focused attention for the development of existing and future therapies. AREAS COVERED: This review evaluates the suitable animal models of VA, including: mice, rodents and non-human primates. It focuses particularly on the possibilities and limitations of these in vivo models for the effective development of VA therapies. EXPERT OPINION: Hormone replacement therapy (HRT) has been prescribed and successfully used for VA. However, some studies have shown that HRT may be linked to an increased risk of breast cancer, coronary heart diseases and others risks. Thus, there is a growing interest in effective and safe alternatives to VA symptoms. There are, however, a number of things that must be considered for future drug discovery efforts. One major consideration is what animal model should be used and whether the model is appropriate for the study aim. Similarly, research studies must also consider the influencing factors on these animal models, so that these models can effectively mimic the actual disease. The authors also highlight the need to standardize research parameters to produce more reliable and reproducible data.

Resistance and barriers to local estrogen therapy in women with atrophic vaginitis.

INTRODUCTION: Vaginal atrophy results from a decrease in circulating estrogen and is experienced by approximately 50% of postmenopausal women. Its symptoms affect multiple dimensions of genitopelvic health, sexuality, and overall quality of life. Nonhormonal over-the-counter treatments may provide temporary symptom relief, but the condition is progressive, and hormonal treatment may be warranted. AIM: The study aims to review the literature and discuss the impact of atrophic vaginitis and various treatment options, including the resistance and barriers to the use of local estrogen therapy for atrophic vaginitis. This article also aims to provide a greater awareness of the condition and the difficulties in communicating effectively with patients, and to provide strategies to help healthcare professionals acquire effective communication skills to initiate a candid dialogue with patients who may be suffering in silence and may benefit from therapy. METHODS: This review was based on peer-reviewed publications on the topic of atrophic vaginitis and local estrogen therapy identified from key word searches of PubMed, in addition to landmark studies/surveys and treatment guidelines/recommendations on menopause available in the literature and on the Internet. MAIN OUTCOME MEASURES: The main outcomes are the impact of atrophic vaginitis and the various treatment options, including the resistance and barriers to the use of local estrogen therapy. RESULTS: Minimally absorbed local vaginal estrogen therapy enables administration of estrogen doses much lower than systemic doses used for vasomotor symptoms. Local therapy is also the first-line pharmacologic treatment recommended by the North American Menopause and International Menopause Societies. Despite treatment options, the sensitive nature of the condition and embarrassment may prohibit or limit many women from openly discussing symptoms with healthcare professionals. Many are hesitant to initiate hormonal treatment because of safety concerns. CONCLUSIONS: Healthcare professionals should initiate and encourage frank and candid conversation about vaginal atrophy at annual visits and provide follow-up and treatment as needed.

Effects of tibolone on climacteric symptoms and quality of life in breast cancer patients--data from LIBERATE trial.

BACKGROUND: Climacteric symptoms such as hot flushes and vaginal dryness are very common in breast cancer patients, resulting either from age or adjuvant therapy. Tibolone, a synthetic steroid, is effective in reducing these symptoms in healthy post-menopausal women, but this has never been studied in a large breast cancer population. OBJECTIVES: The primary objective of LIBERATE trial was to study safety of tibolone 2.5mg daily versus placebo as primary, in symptomatic breast cancer survivors. The aim of this present paper was to report effects of tibolone on climacteric symptoms, vaginal dryness and health-related quality of life in the study population. This trial is registered with ClinicalTrials.gov, n. NCT00408863. METHODS: The trial was conducted between June 2002 and July 2007. Concerning quality of life variables, a daily Diary Cards during the first three months and the Climacteric Symptoms Form and at each visit were used to register frequency and intensity of hot flushes. Mean vaginal dryness scores were calculated on the basis of individual ratings at baseline and at week 104. A subset of patients assessed their quality of life filling in the Women's Health Questionnaire (WHQ). RESULTS: Of the 3148 women recruited, 3133 received trial medication (1575 in the tibolone group and 1558 in the placebo group). The median duration of treatment was 2.75 years. In total 3098 women (1556 on tibolone, 1542 on placebo) were included in the intention-to-treat (ITT) population for efficacy analysis. Data on vaginal dryness are available for 2144 patients and 883 women (438 on tibolone, 445 on placebo) answered to WHQ. The mean change in number of hot flushes per day was 2.74 (43.1%) in the tibolone group and -1.77 (-27.5%) in the placebo group (p<0.0001) at week 12 and -4.62 (-65.6%) on tibolone as compared to -3.73 (-52.5%) on placebo (p<0.0001) at week 104. For the composite score the mean changes at week 12 were -0.19 (-10.6%) and -0.14 (-7.7%), respectively (p=0.0006). Vaginal dryness score improved at week 104 in the tibolone group as compared to placebo (-0.46 versus -0.29, respectively; p<0.0001). Across the assessments up to two years with WHQ, tibolone was more effective than placebo in improving sexual health, sleep quality and mood domains. Women using tamoxifen showed less improvement in climacteric symptoms with tibolone, than women only receiving tibolone without any adjuvant therapy. CONCLUSION: The results of the LIBERATE trial show that tibolone is effective in symptomatic breast cancer patients and improves their quality of life. However, this finding should be judged within the context of the main outcome of the trial, showing that tibolone increases the risk of recurrence. The use of tibolone in women with breast cancer will remain contraindicated and any off-label use incurs a now proven risk.

Vaginitis.

Bacterial vaginosis, trichomoniasis, and vulvovaginal candidiasis are the most common infectious causes of vaginitis. Bacterial vaginosis occurs when the normal lactobacilli of the vagina are replaced by mostly anaerobic bacteria. Diagnosis is commonly made using the Amsel criteria, which include vaginal pH greater than 4.5, positive whiff test, milky discharge, and the presence of clue cells on microscopic examination of vaginal fluid. Oral and topical clindamycin and metronidazole are equally effective at eradicating bacterial vaginosis. Symptoms and signs of trichomoniasis are not specific; diagnosis by microscopy is more reliable. Features of trichomoniasis are trichomonads seen microscopically in saline, more leukocytes than epithelial cells, positive whiff test, and vaginal pH greater than 5.4. Any nitroimidazole drug (e.g., metronidazole) given orally as a single dose or over a longer period resolves 90 percent of trichomoniasis cases. Sex partners should be treated simultaneously. Most patients with vulvovaginal candidiasis are diagnosed by the presence of vulvar inflammation plus vaginal discharge or with microscopic examination of vaginal secretions in 10 percent potassium hydroxide solution. Vaginal pH is usually normal (4.0 to 4.5). Vulvovaginal candidiasis should be treated with one of many topical or oral antifungals, which appear to be equally effective. Rapid point-of-care tests are available to aid in accurate diagnosis of infectious vaginitis. Atrophic vaginitis, a form of vaginitis caused by estrogen deficiency, produces symptoms of vaginal dryness, itching, irritation, discharge, and dyspareunia. Both systemic and topical estrogen treatments are effective. Allergic and irritant contact forms of vaginitis can also occur.