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Maturitas Jun 2014To evaluate the efficacy and safety of ospemifene, a novel selective oestrogen receptor modulator, in the treatment of vaginal dryness in postmenopausal women with... (Randomized Controlled Trial)
Randomized Controlled Trial
Ospemifene, a non-oestrogen selective oestrogen receptor modulator for the treatment of vaginal dryness associated with postmenopausal vulvar and vaginal atrophy: a randomised, placebo-controlled, phase III trial.
OBJECTIVE
To evaluate the efficacy and safety of ospemifene, a novel selective oestrogen receptor modulator, in the treatment of vaginal dryness in postmenopausal women with vulvovaginal atrophy (VVA).
STUDY DESIGN
A 12 week, multicentre, randomised, double-blind, parallel-group phase III study of women (40-80 years) with VVA and self-reported vaginal dryness as their most bothersome symptom.
MAIN OUTCOME MEASURES
The co-primary efficacy endpoints were the change from baseline to Week 12 in (1) percentage of parabasal cells in the maturation index (MI), (2) percentage of superficial cells in the MI, (3) vaginal pH, and (4) severity of vaginal dryness. Safety assessments included physical examination, cervical Papanicolaou test and clinical laboratory analyses. Endometrial thickness and histology was also assessed.
RESULTS
A total of 314 women were randomised to once-daily ospemifene 60 mg/day (n=160) or placebo (n=154). Significant improvements in the percentages of parabasal and superficial cells in the MI and vaginal pH were observed with ospemifene compared with placebo (p<0.001 for all parameters). The mean change from baseline in severity score of vaginal dryness reported by women receiving ospemifene compared with those receiving placebo approached statistical significance (p=0.080). Improvements in each of the four co-primary endpoints with ospemifene were statistically significant compared to placebo in the per protocol population. The majority of treatment-emergent adverse events were considered mild to moderate in severity.
CONCLUSIONS
Once-daily oral ospemifene 60 mg was effective for the treatment of VVA in postmenopausal women with vaginal dryness.
Topics: Aged; Atrophy; Double-Blind Method; Dyspareunia; Female; Humans; Hydrogen-Ion Concentration; Middle Aged; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vaginal Diseases; Vulva
PubMed: 24679891
DOI: 10.1016/j.maturitas.2014.02.015 -
Climacteric : the Journal of the... Aug 2013Vaginal atrophy is a common chronic condition affecting up to 57% of postmenopausal women. The decrease in estrogen following cessation of menses can lead to bothersome... (Review)
Review
Vaginal atrophy is a common chronic condition affecting up to 57% of postmenopausal women. The decrease in estrogen following cessation of menses can lead to bothersome symptoms that include vaginal dryness and irritation, pain and burning during urination (dysuria), urinary tract infections, and pain (dyspareunia) and bleeding during sexual activities. These symptoms can be safely and effectively managed with the use of local estrogen therapy, which reduces the risks associated with long-term systemic hormone therapy. The ultra-low-dose 10 μg estradiol vaginal tablet is the lowest approved dose available and has an annual estradiol exposure of only 1.14 mg. Its development addresses recommendations from regulatory agencies and women's health societies regarding the use of the lowest hormonal dose. The 10 μg vaginal tablet displays minimal estradiol absorption, causes no increased risk of endometrial hyperplasia or carcinoma, and provides significant symptom relief. The clinical evidence presented here may offer greater reassurance to health-care professionals and postmenopausal women that vaginal atrophy can be treated safely and effectively.
Topics: Administration, Intravaginal; Atrophy; Dyspareunia; Estradiol; Female; Humans; Postmenopause; Randomized Controlled Trials as Topic; Treatment Outcome; Vagina; Vaginal Creams, Foams, and Jellies; Vaginal Diseases
PubMed: 23848490
DOI: 10.3109/13697137.2013.807606 -
Maturitas May 2017This paper reviews the efficacy, safety, and systemic absorption of estradiol with TX-004HR, an investigational, low-dose 17β-estradiol vaginal softgel capsule,... (Review)
Review
This paper reviews the efficacy, safety, and systemic absorption of estradiol with TX-004HR, an investigational, low-dose 17β-estradiol vaginal softgel capsule, designed to treat vulvar and vaginal atrophy (VVA) in postmenopausal women, with an improved user experience. In phase 2 (NCT02449902) and phase 3 REJOICE (NCT02253173) studies, TX-004HR significantly improved the proportions of vaginal superficial and parabasal cells and vaginal pH, and in the phase 3 study decreased the severity of dyspareunia, vaginal dryness, and vulvar and/or vaginal itching or irritation. In two randomized, phase 1 trials, estradiol C and AUC were significantly lower with 10μg and 25μg TX-004HR than with the same doses of an approved vaginal estradiol tablet. A substudy (n=72) of the REJOICE trial showed that estradiol C and AUC with 4μg and 10μg TX-004HR were not different from placebo on days 1 and 14. While TX-004HR 25μg was associated with higher C and AUC versus placebo on days 1 and 14, these levels remained within the postmenopausal range. Estradiol day-84 values for all three doses were not different from placebo, demonstrating no estradiol accumulation. All TX-004HR doses were well tolerated and had an acceptable safety profile in all reviewed studies. The local vaginal efficacy of TX-004HR was significantly better than that of placebo, while the overall safety profile was similar to that of placebo. Negligible to very low systemic estradiol absorption was observed whether given at 4, 10, or 25μg. If approved, TX-004HR may be an alternative option for women with symptomatic VVA without increasing mean systemic estradiol absorption above postmenopausal levels.
Topics: Absorption, Physiological; Administration, Intravaginal; Atrophy; Capsules; Double-Blind Method; Dyspareunia; Estradiol; Estrogen Replacement Therapy; Estrogens; Female; Humans; Postmenopause; Vagina; Vaginal Diseases; Vulva; Vulvar Diseases
PubMed: 28364869
DOI: 10.1016/j.maturitas.2017.02.008 -
The Journal of Sexual Medicine Jun 2013Atrophic vaginitis is a common occurrence, particularly among postmenopausal women; however, few seek or receive treatment. One therapeutic solution is topically applied... (Comparative Study)
Comparative Study Randomized Controlled Trial
Evaluation of the efficacy and safety of hyaluronic acid vaginal gel to ease vaginal dryness: a multicenter, randomized, controlled, open-label, parallel-group, clinical trial.
INTRODUCTION
Atrophic vaginitis is a common occurrence, particularly among postmenopausal women; however, few seek or receive treatment. One therapeutic solution is topically applied products. Estrogen-based treatments have been shown to be effective; however, many patients are reluctant to use such formulations due to health concerns, hence the need to assess the efficacy of acceptable alternatives.
AIM
This multicenter, randomized, controlled, open-label, parallel-group clinical trial set out to evaluate the efficacy and safety of hyaluronic acid vaginal gel to treat vaginal dryness compared with estriol cream in postmenopausal women.
METHODS
One hundred forty-four subjects were randomized, 72 to the test group treated with hyaluronic acid vaginal gel (Hyalofemme) and 72 to the control group treated with estriol cream (Ovestin). Treatment in both groups was applied by means of a device once every 3 days for a total of 10 applications over 30 days.
MAIN OUTCOME MEASURES
Efficacy was measured by grading vaginal dryness and three other vaginal symptoms on a visual analog scale. Safety assessments included vital signs, laboratory examinations of the vaginal microecosystem, vaginal pH value, vaginal B ultrasound, and incidence of adverse events. Assessments were performed at baseline, by telephone after the third application, and at the final visit.
RESULTS
Both hyaluronic acid vaginal gel and estriol cream can significantly improve the clinical symptoms of vaginal dryness in postmenopausal women, with improvement rate of 84.44% and 89.42%, respectively, after 10 applications, without statistically significant difference between them.
CONCLUSION
Both hyaluronic acid vaginal gel and estriol cream are effective in the treatment of vaginal dryness. Hyaluronic acid vaginal gel may be considered as a valid alternative to estrogen-based treatments in relieving the symptoms of vaginal dryness.
Topics: Administration, Intravaginal; Adult; Aged; Atrophic Vaginitis; China; Estriol; Female; Humans; Hyaluronic Acid; Middle Aged; Postmenopause; Time Factors; Treatment Outcome; Vagina; Vaginal Creams, Foams, and Jellies
PubMed: 23574713
DOI: 10.1111/jsm.12125 -
European Journal of Obstetrics,... Nov 2015To retrospectively evaluate the efficacy of high-dose-rate brachytherapy of vaginal intraepithelial neoplasia with a special focus on analysis of toxicity.
OBJECTIVE
To retrospectively evaluate the efficacy of high-dose-rate brachytherapy of vaginal intraepithelial neoplasia with a special focus on analysis of toxicity.
STUDY DESIGN
Twenty consecutive patients were irradiated with brachytherapy of vaginal intraepithelial neoplasia with component ca in situ (N=3). Late complications of the vagina graded using the CTCAE v.3.0. General assessment three-step scale was introduced for simplicity of analysis.
RESULTS
The median age was 57 years (range: 28-80 years). The median follow-up time was 39 months (range: 14-115 months). Vaginal intraepithelial neoplasia recurrence was observed in 1 patient. The 3-year disease free survival rate was 90% (95% confidence interval [CI]: 71-100%). Observed late side effects: libido grades 1-2 in 15 (75%), vaginal discharge grade 2 (pad use indicated) in 2 (10%), dryness grade 2 (dyspareunia) in 7 (35%), mucositis grades 2-3 in 6 (30%), stenosis grades 2-3 in 7 (35%) and vaginitis grades 2-3 in 4 (20%) cases. General assessment was good in 9 (45%), average in 2 (10%), and bad in 9 (45%) patients. Treatment dose affected the toxicity (p=0.05). In groups of patients irradiated with biologically equivalent dose (assuming α/β=3Gy) of 47.3-63Gy and ≥70Gy, the risk of poor or moderate toxicity amounted to 16.7% (95% CI: 0-47%) and 71.4% (95% CI: 48-95%), respectively.
CONCLUSION
Brachytherapy revealed to be effective method of vaginal intraepithelial neoplasia treatment, but applying EQD2≥70Gy into vagina generates unacceptable toxicity.
Topics: Adult; Aged; Aged, 80 and over; Brachytherapy; Carcinoma in Situ; Female; Humans; Middle Aged; Radiotherapy Dosage; Retrospective Studies; Vaginal Neoplasms
PubMed: 26334358
DOI: 10.1016/j.ejogrb.2015.08.018 -
Climacteric : the Journal of the... 2016Menopausal symptoms are associated with a negative impact on the quality of life, leading women to seek medical treatment. Obesity has been linked to higher levels of...
OBJECTIVE
Menopausal symptoms are associated with a negative impact on the quality of life, leading women to seek medical treatment. Obesity has been linked to higher levels of menopausal symptoms such as hot flushes. This assessment will explore whether the prevalence and bother of hot flushes and vaginal dryness change from pre- to post-bariatric surgery among obese midlife women.
METHODS
This study is a longitudinal analysis of data from 69 women (ages 35-72 years) undergoing bariatric surgery with reported reproductive histories and menopausal symptoms at preoperative and 6-month postoperative visits. Prevalence of and degree of bother of hot flushes and vaginal dryness at pre- and post-surgery were compared using McNemar's test and Wilcoxon signed-rank test.
RESULTS
The reported degree of bother of symptoms associated with hot flushes decreased from pre- to post-surgery (p < 0.01). There was no significant change in the prevalence of hot flushes or vaginal dryness in the overall study sample.
CONCLUSIONS
The degree of bother of symptoms associated with hot flushes among midlife women may decrease after bariatric surgery. These results highlight important secondary gains, including less bothersome menopausal symptoms, for women who choose bariatric surgery for weight loss.
Topics: Adult; Aged; Bariatric Surgery; Body Mass Index; Female; Hot Flashes; Humans; Logistic Models; Longitudinal Studies; Menopause; Middle Aged; Obesity; Prospective Studies; Quality of Life; Surveys and Questionnaires; Vaginal Diseases
PubMed: 26555182
DOI: 10.3109/13697137.2015.1094782 -
Climacteric : the Journal of the... Feb 2019This study aimed to investigate the prevalence of vaginal atrophy (VA) in women across the menopausal age.
OBJECTIVES
This study aimed to investigate the prevalence of vaginal atrophy (VA) in women across the menopausal age.
METHODS
A multicenter cross-sectional investigation was performed on 747 females, 40-55 years of age, in 30 outpatient public services across the nation. The VA diagnosis was based on the combination of patient sensation of vaginal dryness, an objective sign of VA, and pH >5.
RESULTS
VA was diagnosed in 36.8% of women. Prevalence ranged from 19.2% (40-45 year olds) to 53.8% (52-55 year olds). pH >5 (37.5%) was less prevalent than isolated VA symptoms or signs. Vaginal dryness (64.0%) was the most prevalent symptom followed by dyspareunia (54.5%), itching (38.5%) burning (38.3%), and dysuria (28.9%). Prevalence of vaginal signs declined from vaginal dryness (60.3%) to vaginal thinning (54.5%), vaginal pallor (47.4%), presence of petecchiae (15.7%), and mucosa fragility (15.1%). Most signs and symptoms showed an age-related increase in frequency and intensity. VA was independently associated (R = 0.139; p < 0.0001) with age (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.03-1.13), being in postmenopause (OR 3.45; 95% CI 2.29-5.19), and presence of vasomotor symptoms (OR 3.10; 95% CI 2.09-4.60).
CONCLUSION
VA and its symptoms are common in women across the menopausal age. VA identification may favor early management and treatment.
Topics: Adult; Atrophy; Cross-Sectional Studies; Dyspareunia; Female; Humans; Italy; Logistic Models; Middle Aged; Perimenopause; Prevalence; Vagina; Vaginal Diseases
PubMed: 30601037
DOI: 10.1080/13697137.2018.1529748 -
Obstetrics and Gynecology Dec 1995To describe vaginal anatomy related to sexual function in women.
OBJECTIVE
To describe vaginal anatomy related to sexual function in women.
METHODS
One hundred four women presenting for gynecologic care (mean age 55.8 years) completed questionnaires assessing sexual function and underwent measurements of vaginal caliber and length, and grading of vulvovaginal atrophy.
RESULTS
Women who were not currently sexually active had a higher mean body mass index. Current sexual activity was not associated with differences in vaginal length or introital caliber. Among 73 sexually active women, 30 had one or both symptoms of dyspareunia and vaginal dryness, and 43 had neither symptom. Menopausal status, current use of estrogen, introital caliber, and vaginal length were not different in women with dyspareunia, vaginal dryness, or both when compared to women having neither symptom. Premenopausal women with dyspareunia, vaginal dryness, or both had significantly higher global sexual function scores, reflecting worse sexual function, when compared with premenopausal women without these symptoms (0.61 +/- 0.16 versus 0.46 +/- 0.15, respectively; P = .02); however, there was no significant difference in postmenopausal women (0.60 +/- 0.12 versus 0.61 +/- 0.12).
CONCLUSION
Vaginal anatomy, measured by introital caliber, length, and vulvovaginal atrophy, does not correlate well with sexual function, particularly symptoms of dyspareunia and vaginal dryness.
Topics: Adult; Coitus; Dyspareunia; Female; Humans; Middle Aged; Vagina
PubMed: 7501345
DOI: 10.1016/0029-7844(95)00291-x -
Post Reproductive Health Mar 2019The aim of this overview was to evaluate the effectiveness of phytoestrogens on vaginal health and dyspareunia in peri- and post-menopausal women. (Review)
Review
OBJECTIVE
The aim of this overview was to evaluate the effectiveness of phytoestrogens on vaginal health and dyspareunia in peri- and post-menopausal women.
MATERIAL AND METHODS
Three databases including MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials were from inception to August 2017.
RESULT
Two systematic reviews and 11 RCTs were included in the overview. According to the findings, isoflavones increased the maturation value and attenuated the vaginal atrophy in the post-menopausal women. Topical isoflavones had beneficial effects on the vaginal atrophy. Similar efficacy was found in Pueraria mirifica and conjugated estrogen cream on dryness ( p = 0.277), soreness ( p = 0.124) and irritation ( p = 0.469), as well as discharge ( p = 0.225) and dyspareunia ( p = 0.089). However, the conjugated estrogen cream was more effective compared to Pueraria mirifica ( p > 0.005) regarding maturation index improvement. Comparison of fennel 5% vaginal cream and placebo gel showed significant difference in superficial cells ( p < 0.01), parabasal cells ( p < 0.01) and intermediate cells ( p < 0.01), whereas no difference was found between the oral fennel and placebo in terms of superficial, parabasal and intermediate cells as well as Maturation value. Administration of 80 mg red clover oil had a significant effect on superficial ( p < 0.005), intermediate ( p < 0.005) and parabasal and vaginal dryness ( p < 0.005) compared to the placebo. Flaxseed had also a trivial effect on maturation value. Genistein had a more prominent effect on the genital score. The severity of dyspareunia decreased by 27%.
CONCLUSION
Phytoestrogens have various effects based on administration route and type on the vaginal atrophy.
Topics: Atrophy; Dyspareunia; Female; Flax; Foeniculum; Gels; Humans; Isoflavones; Perimenopause; Phytoestrogens; Plant Preparations; Postmenopause; Pueraria; Trifolium; Vagina; Vaginal Creams, Foams, and Jellies
PubMed: 30786797
DOI: 10.1177/2053369118823365 -
Physiological Reports Aug 2023Loss of estrogen as a result of aging, pelvic cancer therapy, genetics, or eating disorders affects numerous body systems including the reproductive tract. Specifically,...
Loss of estrogen as a result of aging, pelvic cancer therapy, genetics, or eating disorders affects numerous body systems including the reproductive tract. Specifically, a chronic hypoestrogenic state fosters debilitating vaginal symptoms like atrophy, dryness, and dyspareunia. Current treatment options, including vaginal estrogen and hyaluronan (HA), anecdotally improve symptoms, but rectifying mechanisms are largely understudied. In order to study the hypoestrogenic vaginal environment, in particular the extracellular matrix (ECM), as well as understand the mechanisms behind current treatments and develop new therapies, we characterized a reliable and reproducible animal model. Bilateral ovariectomies (OVX) were performed on 9-week-old CD1 mice. After 1 month of estrogen loss due to ovarian removal, a phenotype that is similar to human vaginal tissue in an estrogen reduced state was noted in mice compared to sham-operated controls. The uterine to body weight ratio decreased by 80% and vaginal epithelium was significantly thinner in OVX compared to sham mice. Estrogen signaling was altered in OVX, but submucosal ERα localization did not reach statistical differences. HA localization in the submucosal area was altered and CD44 expression decreased in OVX mice. Collagen turn-over was altered following OVX. The inflammation profile was also disrupted, and submucosal vaginal CD45 and F4/80 cell populations were significantly reduced in the OVX mice. These results show altered cellular and molecular changes due to reduced estrogen levels. Developing new treatments for hypoestrogenic vaginal symptoms rely on better understanding of not only the cellular changes, but also the altered vaginal ECM environment. Further studies using this mouse model has the potential to advance women's vaginal health treatments and aid in understanding the interplay between organ systems in both healthy, aged, and diseased states.
Topics: Humans; Mice; Female; Animals; Aged; Vagina; Estrogens; Receptors, Estrogen; Uterus; Ovariectomy
PubMed: 37549960
DOI: 10.14814/phy2.15762