Atrophy In Postmenopausal Women Research Articles

One-year long-term safety extension study of ospemifene for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus

The aim of this study was to assess the safety of ospemifene, a novel selective estrogen receptor modulator, for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus. In this multicenter, randomized, double-blind, placebo-controlled, long-term safety extension study, nonhysterectomized women aged 40 to 80 years (n = 180) received daily oral doses of placebo, ospemifene 30 mg/day, or ospemifene 60 mg/day for 40 weeks (continued as blinded treatments from the initial 12-week pivotal efficacy study of ospemifene). The total treatment period was 52 weeks. Safety assessments included adverse events, cervical Papanicolaou tests, endometrial histology, endometrial thickness, gynecological examination, breast palpation, mammography, physical examination, and clinical safety laboratory assessments. No clinically significant adverse changes in safety assessments were observed in any treatment group. Most treatment-emergent adverse events were mild or moderate in severity. Hot flushes, the most frequently occurring treatment-emergent adverse event related to the study drug, had a low discontinuation rate (1.6%). No study participants discontinued because of endometrial or cervical pathology; no endometrial findings were clinically meaningful. On week 52, more than 95% of endometrial biopsy samples either were classified as atrophic or inactive or had insufficient tissue for diagnosis. There were no treatment-emergent adverse events of pelvic organ prolapse or venous thromboembolism. No cases of endometrial hyperplasia or carcinoma were observed. Only three participants (1.7%) taking ospemifene experienced vaginal bleeding or spotting, which was self-limiting. Daily doses of ospemifene 30 mg and ospemifene 60 mg yielded few treatment-emergent adverse events and demonstrated no significant endometrial changes during the 1-year treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus.

Effective treatment of vaginal atrophy with isoflavone vaginal gel

ObjetiveTo assess efficacy and tolerability of a isoflavone (Glycine max L. Merr.) vaginal gel to the treatment of vaginal atrophy in postmenopausal women. MethodsThe double-blind, randomized, placebo-controlled, clinical trial. Ninety women were treated for 12 weeks with isoflavone vaginal gel 4% (1g/day) and a placebo gel and conjugated equine estrogen cream (0.3mg/day). After 4 and 12 weeks, the vaginal atrophy symptoms were classified at none, mild, moderate and severe and the vaginal cytology were taken to determine the maturation value. The endometrial safety (by transvaginal ultrasonography) was evaluated through at screening and the end of the trial. ResultsIsoflavone vaginal gel appears to be effective for relief of vaginal dryness and dyspareunia symptons and an increase in the intermediate and superficial cells was noted. These results were similar to the effects with use of conjugated equine estrogens and superior to placebo gel. No changes in endometrial thickness, sera FSH and estradiol levels were observed at study endpoint. ConclusionGlycine max (L.) Merr. at 4% vaginal gel on a daily basis in postmenopausal women led to improvements in vaginal atrophy symptoms and a significant increase in cell maturation values. Isoflavones proved good treatment options for relief of vulvovaginal symptoms especially in women who do not wish to use hormonal therapy or have contra-indications for this treatment.

M456 ENDOMETRIAL ATROPHY IN POSTMENOPAUSAL WOMEN WITH ENDOMETRIAL THICKNESS > 5MM

International Journal of Gynecology & ObstetricsVolume 119, Issue S3 p. S677-S678 Poster presentations M456 ENDOMETRIAL ATROPHY IN POSTMENOPAUSAL WOMEN WITH ENDOMETRIAL THICKNESS > 5MM G.E. Scribano, G.E. ScribanoSearch for more papers by this authorV. Villani, V. VillaniSearch for more papers by this authorT. Canino, T. CaninoSearch for more papers by this authorV. Spina, V. SpinaSearch for more papers by this authorM. Giovannini, M. GiovanniniSearch for more papers by this author G.E. Scribano, G.E. ScribanoSearch for more papers by this authorV. Villani, V. VillaniSearch for more papers by this authorT. Canino, T. CaninoSearch for more papers by this authorV. Spina, V. SpinaSearch for more papers by this authorM. Giovannini, M. GiovanniniSearch for more papers by this author First published: 22 October 2012 https://doi.org/10.1016/S0020-7292(12)61646-4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume119, IssueS3Abstracts of XX FIGO World Congress of Gynecology and ObstetricsOctober 2012Pages S677-S678 RelatedInformation

Black cohosh improves vaginal atrophy in postmenopausal women

Objective To investigate the efficacy of cimicifuga racemosa in reatment of postmenopausal vaginal atrophy.Methods Seventy 45-60 years old women,who had menopause for more than one year and symptoms of postmenopausal vaginal atrophy,were randomly divided into two groups: observation group(n=40) and placebo group(n=30).The observation group was given cimicifuga racemosa(remifemin) 20 mg twice a day for 12 weeks.The placebo group was given one calcium carbonate and vitamin D3 tablet twice a day for 12 weeks.The serum levels of follicle stimulation hormone(FSH) and estradiol(E2) and thickness of endometrium were examined before and after treatment.The vaginal pH value,maturation degree of vaginal exfoliated cells,and atrophic vaginitis evaluating score were used to assess the therapeutic effects.The adverse effects were recorded.Results In the observation group there were no significant differences in FSH and E2 levels and endometrium thickness before and after treatment(P0.05).The vaginal pH value showed a decreasing tendency and the maturation degree of vaginal exfoliated cells showed an increasing tendency after treatment in the observation group,but there were no significant differences(P0.05).The atrophic vaginitis evaluating score was significantly higher before treatment compared with that after treatment(6.0±0.6 vs 3.3±0.6,P0.05).During the remifemin treatment,the blood routine,urine test,heart rate,blood pressure,body mass and other indicators were not significantly different before and after treatment in the observation group(P0.05).There were no adverse effects during the treatment.Conclusion The remifemin shows certain therapeutic effects for vaginal atrophy in postmenopausal women.

Open, Non-controlled Clinical Studies to Assess the Efficacy and Safety of a Medical Device in Form of Gel Topically and Intravaginally Used in Postmenopausal Women with Genital Atrophy

Menopause is often associated with vaginal atrophy and related symptoms, such as vaginal dryness, burning, itching, and dyspareunia, decrease in libido and in general a decrease in the quality of life. The common treatment up to the 1990's has been the oral hormone replacement therapy (HRT), but this treatment has been consequently re-considered due to its adverse effects. Topical estrogenic products have been subsequently developed to minimize the systemic adverse effects of the oral HRT, but they are still considered at risk in case of prolonged use. As an alternative, two clinical trials were performed to investigate the effects of a medical device in the form of a gel, containing hyaluronic acid, liposomes, phytoestrogens from Humulus lupulus extract, and Vitamin E, with the aim of testing its safety and efficacy in post-menopausal women with urogenital atrophy. The first pilot study confirmed in 10 women the good safety profile, both locally and systemically, of the device applied on the external genitals at the dose of 1-2 g/day for 30 days. The second study was carried out, according to a multicenter, open, non-controlled design, in 100 post-menopausal women assigned to the vaginal application of 2.5 g of gel/day for 1 week followed by two applications/week for 11 weeks. The primary end-point was the evaluation of vaginal dryness assessed by a Visual Analogue Scale both by the investigator and the subject. Secondary endpoints were the evaluation of all other symptoms and signs associated with atrophic vaginitis (itching, burning, dyspareunia, vaginal inflammation/oedema and rash assessed by a 4-point scale and presence of vaginal abrasions and disepithelialisation), and the recording of adverse events during the study. At the end of the treatment, an overall judgment on the efficacy and safety of the device was made by the investigator and a judgment on the acceptability of the treatment was made by the subjects. The results showed a marked effect of the tested product on the vaginal dryness and on all other symptoms and signs with statistically significant reductions since the first week of treatment. No treatment-related adverse events were complained by the subjects and the treatment course showed a high level of acceptability by the subjects. This device could be considered an effective and safe alternative treatment of genital atrophy in post-menopausal women, especially when HRT is not recommended.

Topical oxytocin reverses vaginal atrophy in postmenopausal women: a double-blind randomized pilot study

Oxytocin is a peptide hormone produced in the hypothalamus and it is best known for its role in labour and lactation. This double-blind, randomized study was performed at Huddinge Hospital of Karolinska Institutet, Stockholm in order to test the effectiveness of topical oxytocin gel in women with postmenopausal vaginal atrophy. Twenty postmenopausal women (at least two years after menopause) with symptoms of vaginal atrophy such as vaginal dryness, pain, itching, discomfort and bleeding during intercourse were enrolled in the study when visual inspection of the vagina had confirmed that their mucosa was atrophic. The participants were randomized to intravaginal treatment with either oxytocin or placebo gel for seven days. Before and after treatment, a gynaecological examination and a visual and colposcopic inspection of the vagina were performed, biopsies from the vaginal mucosa were taken and blood samples were collected for analysis of circulating levels of estradiol and oxytocin. Prior to treatment, visual and colposcopic inspection showed that all of the 20 participants had an atrophic vaginal mucosa. After treatment with the oxytocin gel, the examination showed that the vaginal epithelium of seven of the 10 participants in the oxytocin group had become healthier and normalized. No change in these parameters was observed among the 10 participants in the placebo group. This difference between the oxytocin and placebo groups was significant (P= 0.003). Seven participants in the active group and four in the placebo group reported relief of symptoms of vaginal atrophy after seven days of applying the gel. The effect of oxytocin to normalize the morphological appearance of the vaginal mucosa was almost significant when compared with the placebo group (P= 0.07). There was no significant difference between the circulating levels of estradiol and oxytocin in both the oxytocin and placebo groups before and after treatment. None of the participants reported any side-effects. Topical treatment with oxytocin appears to improve vaginal atrophy in postmenopausal women. A limitation of this pilot study is that it was based on a small study population hence the results should be regarded with caution. Larger studies are in progress to establish the possibility of using oxytocin as a clinical treatment for vaginal atrophy.

Utility of p16, Ki-67, and HPV Test in Diagnosis of Cervical Intraepithelial Neoplasia and Atrophy in Women Older Than 50 Years With 3- to 7-Year Follow-up

Differentiating cervical intraepithelial neoplasia (CIN) from atrophy in postmenopausal women based on morphology alone is challenging. p16 and Ki-67 help distinguish CIN2/3 from atrophy. The goal of this study is to further characterize the utility of p16, Ki-67, and human papillomavirus (HPV) tests in women older than 50 years, particularly in CIN1. The authors retrospectively identified cervical specimens from three, 1-year time periods. Included were cases from women older than 50 years with benign diagnoses, atrophy, and CIN. Slides were stained with p16 and Ki-67 and graded as positive or negative. Medical records were reviewed for cytology, HPV test, and histopathologic diagnoses from the time of biopsy to 2010. A total of 97 cervical samples were included. In all, 34 (74%) CIN1 cases were negative for p16 and Ki-67. Of CIN1 cases with positive HPV tests, only 1/10 (10%) had positive p16 staining versus 2/2 (100%) of CIN2/3 cases. Of 39 women with CIN1 who had follow-up data available, 4 (10%) had subsequent histologic progression to CIN2/3 and none developed invasive disease. In our study, the majority of cases (74%) diagnosed as CIN1 in women ≥ 50 years are negative for p16 and Ki-67 and do not progress to high-grade dysplasia during 3- to 7-year follow-up. A combination of morphology, p16, and Ki-67 on cervical specimens in women older than 50 years, and furthermore, use of these stains on Pap tests in combination with HPV testing may help distinguish CIN from atrophy and reduce unnecessary invasive follow-up testing.

Intravaginal dehydroepiandrosterone (prasterone), a highly efficient treatment of dyspareunia

Objective To examine the effect of intravaginal dehydroepiandrosterone (DHEA) on pain at sexual activity (dyspareunia) identified as the most bothersome symptom of vaginal atrophy in postmenopausal women at both screening and day 1.Methods 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 severity of dyspareunia in 114 postmenopausal women who had identified dyspareunia as their most bothersome symptom of vaginal atrophy, while meeting the criteria for superficial cells ≤ 5% and pH > 5.0 at both screening and day 1.Results At the standard duration of 12 weeks of treatment, increasing doses of 0.25%, 0.5% and 1.0% DHEA decreased the percentage of parabasal cells by 48.6 ± 6.78%, 42.4 ± 7.36% and 54.9 ± 6.60% (p < 0.0001 vs. placebo for all) with no change with placebo (p = 0.769). The effects on superficial cells and pH were also highly significant compared to placebo at all DHEA doses. The severity score of pain at sexual activity decreased by 0.5, 1.4, 1.6 and 1.4 units in the placebo and 0.25%, 0.5% and 1.0% DHEA groups, respectively, with the p value of differences from placebo ranging from 0.0017 to < 0.0001.Conclusions Intravaginal DHEA, through local estrogen and androgen formation, causes a rapid and highly efficient effect on pain at sexual activity without systemic exposure of the other tissues, thus avoiding the recently reported systemic effects of estrogens.

Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women

The aim of this study was to study the efficacy and safety of ospemifene, a new selective estrogen receptor modulator, in the treatment of vulvovaginal atrophy in postmenopausal women. A randomized, double-blind phase 3 study in which 826 postmenopausal women were randomized 1:1:1 to receive treatment with ospemifene 30 or 60 mg/day or placebo orally for 12 weeks was conducted. The primary inclusion criteria were having 5% or less superficial cells on the vaginal smear (maturation index), vaginal pH greater than 5.0, and at least one moderate or severe symptom of vulvovaginal atrophy. The four coprimary endpoints were the change from baseline to 12 weeks in the percentage of superficial and parabasal cells on the vaginal smear, change in vaginal pH, and change in severity of most bothersome symptom (vaginal dryness or dyspareunia) compared with placebo. All participants were given a nonhormonal vaginal lubricant for use as needed. Ospemifene was statistically significantly superior to placebo in each of the coprimary endpoints at the 60-mg dose. Statistically significant results were achieved for all coprimary endpoints with the 30-mg dose except for dyspareunia. Ospemifene was well tolerated at both doses and demonstrated a favorable safety profile. Ospemifene was shown to be effective and well tolerated for the treatment of the symptoms of vaginal dryness and dyspareunia associated with vulvovaginal atrophy over and above the use of provided lubricants.

Recognizing and Treating Urogenital Atrophy in Postmenopausal Women

Urogenital atrophy resulting from postmenopausal estrogen deficiency has numerous clinical effects, including vaginal dryness, sexual dysfunction, urinary incontinence, and recurrent urinary tract infections (UTIs), all of which can cause significant distress and reduction in quality of life. Although nearly one third to one half of postmenopausal women experience these symptoms, they are often overlooked because patients may be reluctant to discuss them and clinicians fail to screen for them. As these symptoms are unlikely to resolve without treatment, the prompt diagnosis and treatment of urogenital atrophy is essential. Estrogen therapy, administered either locally or systemically, provides significant relief from symptoms related to urogenital atrophy. However, systemic estrogen therapy is contraindicated in some women and may not be accepted in women without other menopausal symptoms. Local low-dose vaginal estrogen therapy, in the form of vaginal estrogen tablets, creams, or rings, has been shown to reduce dyspareunia and vaginal dryness, restore vaginal pH, and restore normal vaginal cytology. All forms of vaginal estrogen therapy are effective and well tolerated, although vaginal tablets and rings may have fewer adverse effects and have higher rates of adherence than creams.

A randomized, placebo- and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women

The primary objective of the Selective estrogen Menopause And Response to Therapy 3 (SMART-3) trial was to compare the efficacy and safety of two doses of bazedoxifene (BZA)/conjugated estrogens (CE) versus placebo for the treatment of moderate to severe vulvar/vaginal atrophy (VVA) associated with menopause. This was a phase 3, multicenter, double-blind, randomized, placebo-controlled, and active comparator-controlled study. Healthy postmenopausal women (n = 664; aged 40-65 y) were randomized to BZA 20 mg/CE 0.625 mg, BZA 20 mg/CE 0.45 mg, BZA 20 mg, or placebo once daily for 12 weeks. Changes in vaginal maturation, vaginal pH, and severity of the most bothersome symptom of VVA from baseline were assessed at screening and at weeks 4 and 12. Adverse events were recorded throughout the study. BZA 20 mg/CE 0.625 or CE 0.45 mg significantly (P < 0.01) increased superficial cells and decreased parabasal cells compared with placebo. Vaginal pH and most bothersome symptom significantly improved with BZA 20 mg/CE 0.625 mg compared with placebo (P < 0.05). Improvements in vaginal dryness were also observed with both BZA/CE doses (P G 0.05). The incidence of treatment-related adverse events were similar across treatment groups. BZA/CE is effective in treating moderate to severe VVA and vaginal symptoms. These data further support the use of a tissue-selective estrogen complex containing BZA/CE as a new menopausal therapy for postmenopausal women.

Lasofoxifene for the prevention and treatment of postmenopausal osteoporosis.

Lasofoxifene is a selective estrogen receptor modulator (estrogen agonist/antagonist) that has completed phase III trials to evaluate safety and efficacy for the prevention and treatment of osteoporosis and for the treatment of vaginal atrophy in postmenopausal women. In postmenopausal women with low or normal bone mineral density (BMD), lasofoxifene increased BMD at the lumbar spine and hip and reduced bone turnover markers compared with placebo. In women with postmenopausal osteoporosis, lasofoxifene increased BMD, reduced bone turnover markers, reduced the risk of vertebral and nonvertebral fractures, and decreased the risk of estrogen receptor-positive breast cancer. In postmenopausal women with low bone mass, lasofoxifene improved the signs and symptoms of vulvovaginal atrophy. Clinical trials show that lasofoxifene is generally well tolerated with mild to moderate adverse events that commonly resolve even with drug continuation. Lasofoxifene has been associated with an increase in the incidence of venous thromboembolic events, hot flushes, muscle spasm, and vaginal bleeding. It is approved for the treatment of postmenopausal women at increased risk for fracture in some countries and is in the regulatory review process in others.

Lasofoxifene, a new selective estrogen receptor modulator for the treatment of osteoporosis and vaginal atrophy

Selective estrogen receptor modulators (SERMs) represent a class with a growing number of compounds that act as either estrogen receptor (ER) agonists or antagonists in a tissue-specific manner. The purpose of this article is to review the effects of lasofoxifene, a new-generation SERM that has completed the Phase III development program for the prevention and treatment of osteoporosis and vaginal atrophy in postmenopausal women. This compound selectively binds to both ERs with high affinity. Lasofoxifene also has a remarkably improved oral bioavailability with respect to other SERMs such as raloxifene and tamoxifen, owing to increased resistance to intestinal wall glucuronidation. In both preclinical and short-term clinical studies, this compound showed a favorable safety profile and demonstrated a proven efficacy in preventing bone loss and lowering cholesterol levels. More recently, Phase III clinical trials have confirmed the efficacy and safety of this new SERM in the prevention of bone loss and vertebral and nonvertebral fractures. Moreover, in postmenopausal women with osteoporosis, lasofoxifene treatment also reduced ER positive breast cancer risk and the occurrence of vaginal atrophy. With its increased potency and efficacy on the prevention of nonvertebral fractures and its positive effects on the vagina, this new SERM may represent an alternative therapy for osteoporosis in postmenopausal women.

An ultra-low dose (10μg) estradiol vaginal tablet improves signs and symptoms associated with vaginal atrophy

OBJECTIVE: To assess the efficacy of a 10μg 17β-estradiol (E2) vaginal tablet for the treatment of vaginal atrophy in postmenopausal women.DESIGN: This was a 52-week, randomized, double-blind, multicenter, placebo-controlled study. Subjects were randomized 2:1 to receive either a 10μg E2 or a placebo tablet administered vaginally once-daily for the first two weeks of the study and then twice-weekly thereafter. Subjects enrolled in this study (N=309) were non-hysterectomized postmenopausal women ≥45 years of age, ≥2 years after last menses or bilateral oophorectomy, with ≥3 urogenital symptoms (≥1 moderate to severe), ≤5% superficial cells, vaginal pH>5 and endometrial thickness <4mm.MATERIALS AND METHODS: Primary efficacy assessments included most bothersome urogenital symptoms, vaginal pH, vaginal cytology and epithelial maturation reported using the Maturation Index [MI] and Value [MV]. At each visit, subjects completed a self-administered questionnaire describing symptoms associated with vaginal atrophy (vaginal dryness, irritation/itching, soreness, dysuria, dyspareunia and bleeding during sexual activity) and symptom severity (coded as not applicable, none=0, mild=1, moderate=2, severe=3). An ANCOVA model was used for between-treatment efficacy comparisons.RESULTS: At baseline, of the 6 most bothersome urogenital symptoms associated with vaginal atrophy, dyspareunia (placebo, 60.8%; E2, 52.5%), vaginal dryness (placebo, 26.5%; E2, 28.4%), and irritation/itching (placebo, 9.8%; E2, 12.3%) were reported by the largest proportions of subjects. At week 12, the changes from baseline in mean score of most bothersome symptom for placebo and E2, respectively, were −0.90 and −1.22 for dyspareunia, −0.85 and −1.22 for vaginal dryness, and −0.80 and −1.20 for irritation/itching. An analysis of the change from baseline in mean composite most bothersome symptom scores showed that vaginal E2 provided significant improvements compared with placebo at week 12 (LOCF, p=0.003), week 8 (p=0.014) and week 52 (LOCF, p=0.004). Significant improvements from baseline with vaginal E2 were demonstrated for MI, MV and vaginal pH at all assessed timepoints compared with placebo (p<0.001).CONCLUSIONS: An ultra-low dose 10μg 17β-estradiol vaginal tablet improves vaginal maturation and provides relief from most bothersome urogenital symptoms associated with estrogen deficiency-induced vaginal atrophy. OBJECTIVE: To assess the efficacy of a 10μg 17β-estradiol (E2) vaginal tablet for the treatment of vaginal atrophy in postmenopausal women. DESIGN: This was a 52-week, randomized, double-blind, multicenter, placebo-controlled study. Subjects were randomized 2:1 to receive either a 10μg E2 or a placebo tablet administered vaginally once-daily for the first two weeks of the study and then twice-weekly thereafter. Subjects enrolled in this study (N=309) were non-hysterectomized postmenopausal women ≥45 years of age, ≥2 years after last menses or bilateral oophorectomy, with ≥3 urogenital symptoms (≥1 moderate to severe), ≤5% superficial cells, vaginal pH>5 and endometrial thickness <4mm. MATERIALS AND METHODS: Primary efficacy assessments included most bothersome urogenital symptoms, vaginal pH, vaginal cytology and epithelial maturation reported using the Maturation Index [MI] and Value [MV]. At each visit, subjects completed a self-administered questionnaire describing symptoms associated with vaginal atrophy (vaginal dryness, irritation/itching, soreness, dysuria, dyspareunia and bleeding during sexual activity) and symptom severity (coded as not applicable, none=0, mild=1, moderate=2, severe=3). An ANCOVA model was used for between-treatment efficacy comparisons. RESULTS: At baseline, of the 6 most bothersome urogenital symptoms associated with vaginal atrophy, dyspareunia (placebo, 60.8%; E2, 52.5%), vaginal dryness (placebo, 26.5%; E2, 28.4%), and irritation/itching (placebo, 9.8%; E2, 12.3%) were reported by the largest proportions of subjects. At week 12, the changes from baseline in mean score of most bothersome symptom for placebo and E2, respectively, were −0.90 and −1.22 for dyspareunia, −0.85 and −1.22 for vaginal dryness, and −0.80 and −1.20 for irritation/itching. An analysis of the change from baseline in mean composite most bothersome symptom scores showed that vaginal E2 provided significant improvements compared with placebo at week 12 (LOCF, p=0.003), week 8 (p=0.014) and week 52 (LOCF, p=0.004). Significant improvements from baseline with vaginal E2 were demonstrated for MI, MV and vaginal pH at all assessed timepoints compared with placebo (p<0.001). CONCLUSIONS: An ultra-low dose 10μg 17β-estradiol vaginal tablet improves vaginal maturation and provides relief from most bothersome urogenital symptoms associated with estrogen deficiency-induced vaginal atrophy.

Postmenopausal vaginal atrophy correlates with decreased estradiol and body mass index and does not depend on the time since menopause

Objective. To evaluate the relationship between morphologic cell characteristics in Papanicolaou (Pap) smears and serum estradiol, body mass index (BMI) and the time elapsed since menopause.Study design. In 92 women Pap smears were grouped into atrophic and mature cell patterns and compared with estradiol, BMI and the time since menopause.Results. Forty-one patients with mature cell pattern were on average 7.1 years from menopause and 51 patients with atrophic pattern 8.2 years, but this difference was not significant. Estradiol in patients with mature cell pattern was significantly higher (52.1 ± 48.5 pmol/l) than in patients with atrophic pattern (25.6 ± 40.0 pmol/l). Similarly, BMI was significantly higher (27.9 ± 4.2 kg/m2) in patients with mature cell pattern than in patients with atrophic pattern (25.7 ± 3.8 kg/m2). There was no significant correlation between the time since menopause and estradiol among patients with mature and atrophic cell pattern. The same was true for the correlation between the time from menopause and BMI in patients with mature and atrophic pattern.Conclusions. Estradiol and BMI are associated with vaginal cell maturation and atrophy in postmenopausal women. Vaginal cell atrophy does not depend on the time since menopause.

Effects of intravaginal dehydroepiandrosterone on vaginal histomorphology, sex steroid receptor expression and cell proliferation in the rat

Objective Recent clinical studies have shown that postmenopausal hormone therapy with estrogen plus progestogen increases breast cancer risk. Moreover, intravaginal estrogen-containing pills, creams and rings lead to significant systemic exposure to estrogen, thus indicating the need for a completely novel approach to alleviate vaginal atrophy in postmenopausal women. Design We have studied the effect of intravaginal application of dehydroepiandrosterone at daily doses of 0.33 mg, 0.66 mg or 1 mg in ovariectomized animals for 2 weeks, with the objective of inducing local beneficial effects in the vagina without significant systemic action. Results After 2 weeks, serum dehydroepiandrosterone, androst-5-ene-3β,17β-diol and dehydroepiandrosterone-sulfate were increased over a 4 h time period, but serum testosterone, estradiol, estrone and dihydrotestosterone remained below detectable levels. The suppository vehicle alone produced minimal epithelial thickening limited to the vaginal distal half. The morphological effects of dehydroepiandrosterone on vaginal mucosa were observed at the lowest dose and consisted mainly of a typical androgenic effect of epithelial mucification. No change in morphological features related to cell proliferation was observed at any dehydroepiandrosterone dose on uterus, mammary gland and skin. At the highest dose, body weight showed a significant decrease, thus indicating a systemic effect on lipid accumulation. Immunohistochemistry for androgen, estrogen alpha and progesterone receptors did not reveal any significant systemic effects in the uterus, mammary gland and skin except some suggestion of increased androgen receptor labeling in mammary gland and skin at the highest dehydroepiandrosterone dose. Conclusion The present data show that intravaginal dehydroepiandrosterone can exert beneficial effects limited to the vagina.

The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women

Menopause: May 2007 - Volume 14 - Issue 3 - p 370-371 doi: 10.1097/gme.0b013e3180533b2a

The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women

To create an evidence-based position statement published by The North American Menopause Society (NAMS) on the role of local vaginal estrogen therapy (ET) for the treatment of vaginal atrophy in postmenopausal women. NAMS followed the general principles established for evidence-based guidelines to create this document. A panel of clinicians and researchers acknowledged to be experts in the field of genitourinary disease was enlisted to review, synthesize, and interpret the current evidence on vaginal ET for vaginal atrophy, develop conclusions, and make recommendations. Their advice was used to assist the NAMS Board of Trustees in publishing this position statement. Randomized controlled trials, albeit limited, have shown that low-dose, local vaginal estrogen delivery is effective and well tolerated for treating vaginal atrophy. All of the low-dose vaginal estrogen products approved in the United States for treatment of vaginal atrophy are equally effective at the doses recommended in labeling. The choice of therapy should be guided by clinical experience and patient preference. Progestogen is generally not indicated when low-dose estrogen is administered locally for vaginal atrophy. Data are insufficient to recommend annual endometrial surveillance in asymptomatic women using vaginal ET. Vaginal ET should be continued for women as long as distressful symptoms remain. For women treated for non-hormone-dependent cancer, management of vaginal atrophy is similar to that for women without a cancer history. For women with a history of hormone-dependent cancer, management recommendations are dependent upon each woman's preference in consultation with her oncologist.

Tibolone for the treatment of moderate to severe vasomotor symptoms and genital atrophy in postmenopausal women

To demonstrate the safety and efficacy of tibolone (1.25 and 2.5 mg) in the treatment of moderate to severe vasomotor symptoms and symptoms associated with vaginal atrophy. A placebo-controlled, double-blind, randomized, multicenter study was conducted on 396 healthy postmenopausal women experiencing a minimum of 7 moderate to severe hot flashes per day (60 per week). Participants were randomized to receive tibolone 1.25 or 2.5 mg or placebo once daily for 12 weeks. Assessments were done at weeks 4, 8, and 12. The severity and frequency of hot flashes were recorded in patient diaries on a daily basis. Tibolone 2.5 mg significantly (P < 0.001) reduced the average number of hot flashes compared with placebo at week 4 (-7.82 vs -5.27), week 8 (-9.71 vs -5.86), and week 12 (-10.14 vs -5.85). The difference between tibolone 1.25 mg and placebo was significant (P < 0.001) at week 8 (-7.96) and week 12 (-8.32). Findings for the average daily severity of hot flashes were similar, with significantly greater reductions at week 4 (P < 0.05) and weeks 8 and 12 (P < 0.001) for tibolone 2.5 mg versus placebo and at weeks 8 and 12 for tibolone 1.25 mg versus placebo (P < 0.001). A menopausal atrophic symptom questionnaire revealed that tibolone 2.5 mg significantly (P < 0.05) reduced nocturia compared with placebo at weeks 4, 8, and 12 and urinary urgency at week 4. Compared with placebo, both doses of tibolone also significantly (P < 0.001) increased the vaginal maturation value from baseline. The overall incidence of adverse events was similar in all treatment groups. Tibolone is effective and well tolerated for the treatment of moderate to severe vasomotor symptoms and the effects of vaginal atrophy associated with menopause.

Lasofoxifene enhances vaginal mucus formation without causing hypertrophy and increases estrogen receptor β and androgen receptor in rats

Lasofoxifene, a new selective estrogen-receptor modulator (SERM), shows efficacy in vaginal and vulvar atrophy in postmenopausal women. Here, we sought to explore the possible mechanisms of action for this effect in comparison with other SERMs using an immature ovariectomized rat model. SERMs (lasofoxifene, raloxifene, and tamoxifen) and 17alpha-ethinyl estradiol were administered orally to immature ovariectomized rats daily for 1 or 4 days. Vaginal and uterine tissues were weighed and processed for histomorphometric measurements, vaginal mucopolysaccharide staining, and immunohistochemistry of 5-bromo-2'-deoxyuridine and steroid receptors. Receptor quantification was determined by a novel ultrasensitive enzyme-linked immunosorbent assay method. Lasofoxifene and raloxifene showed a minimal increase in vaginal and uterine weight, epithelial cell proliferation, and epithelial thickness in comparison with estradiol and tamoxifen. Lasofoxifene significantly enhanced vaginal mucus formation in a dose-dependent manner. Vaginal progesterone receptor protein was increased fivefold by estradiol and all three SERMs tested. 17alpha-Ethinyl estradiol caused a significant decrease in estrogen receptor alpha, but no change with other treatments. Only lasofoxifene significantly increased vaginal estrogen receptor beta and androgen receptor protein levels. These results demonstrated that lasofoxifene stimulated vaginal mucus formation without causing cell proliferation in the rat reproductive tract. These effects may be due to the increased vaginal estrogen receptor beta and androgen receptor levels. This cellular and molecular profile of lasofoxifene in the vagina may account for its efficacy in the treatment of vaginal and vulvar atrophy in postmenopausal women.