Continuous low dose estradiol released from a vaginal ring versus estriol vaginal cream for urogenital atrophy. Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms. A one-year multicenter study of efficacy and safety of a continuous, low-dose, estradiol-releasing vaginal ring (Estring) in postmenopausal women with symptoms and signs of urogenital aging. Evaluation of the efficacy of flaxseed meal and flaxseed extract in reducing menopausal symptoms. A comparative multicenter study of the effects of continuous low-dose estradiol released from a new vaginal ring versus estriol vaginal pessaries in postmenopausal women with symptoms and signs of urogenital atrophy. The effect of vitamin D on vaginal atrophy in postmenopausal women Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet The effect of chinese medicinal herbs in relieving menopausal symptoms in ovariectomized chinese women. Transdermal estradiol gel 0.1% for the treatment of vasomotor symptoms in postmenopausal women Vaginal ring delivering estradiol and progesterone: a possible alternative to relieve climacteric symptoms. Micro-dose transdermal estradiol for relief of hot flushes in postmenopausal Asian women: a randomized controlled trial Efficacy of Low-Dose Estradiol Vaginal Tablets in the Treatment of Atrophic Vaginitis: A Randomized Controlled Trial Effective Treatment of Vaginal Atrophy With an Ultra–Low-Dose Estradiol Vaginal Tablet Non-hormonal treatment of vulvo-vaginal atrophy-related symptoms in post-menopausal women A comparison of raloxifene and calcium plus vitamin D on vaginal atrophy after discontinuation of long-standing postmenopausal hormone therapy in osteoporotic women. A randomized, masked-evaluator, one-year, prospective study. The effect of estradiol vaginal tablet and conjugated estrogen cream on urogenital symptoms in postmenopausal women: a comparative study. Comparing the effects of continuous hormone replacement therapy and tibolone on the genital tract of menopausal women; a randomized controlled trial. Efficacy of vaginally applied estrogen, testosterone, or polyacrylic acid on vaginal atrophy: a randomized controlled trial 17&bgr;‐Estradiol Vaginal Tablet Versus Conjugated Equine Estrogen Vaginal Cream to Relieve Menopausal Atrophic Vaginitis Suppression of vasomotor and vulvovaginal symptoms with continuous oral 17&bgr;‐estradiol Low Dose of Transdermal Estradiol Gel for Treatment of Symptomatic Postmenopausal Women: A Randomized Controlled Trial A prospective randomized comparative study of the effects of intranasal and transdermal 17 beta-estradiol on postmenopausal symptoms and vaginal cytology. Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial.
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 r and omized 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 r and omized 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 OBJECTIVE To assess the efficacy , tolerability , and acceptance of a vaginal ring delivering the equivalent of 50 or 100 microg per day of estradiol ( E2 ) , compared with placebo , for relief of moderate to severe vasomotor symptoms and urogenital symptoms in postmenopausal women . METHODS Women with moderate to severe vasomotor symptoms ( seven or more per day or 56 per week average ) received 13 weeks of treatment with a vaginal ring delivering 50 microg per day E2 ( n = 113 ) or 100 microg per day E2 ( n = 112 ) , or a placebo vaginal ring ( n = 108 ) . Severity of vasomotor symptoms was assessed by a daily diary card and the Greene Climacteric Scale . Urogenital signs and symptoms were evaluated via patient and physician assessment and vaginal cytology . Participant satisfaction with the vaginal ring was evaluated via question naire . RESULTS Vasomotor symptoms significantly improved in both treatment groups , compared with placebo ( P < .05 ) . There was a trend toward greater improvement in patient assessment of urogenital signs with active rings compared with placebo . For women with vaginal atrophy at baseline ( n = 60 ) , the maturation index improved significantly in both treatment groups compared with placebo . Total Greene Climacteric Scale scores significantly improved for both E2 vaginal ring groups ( P < .05 ) compared with placebo . The vaginal rings were well tolerated . Most adverse events were mild or moderate and consistent with estrogen therapy . CONCLUSION A novel vaginal ring delivering the equivalent of 50 or 100 microg per day of E2 significantly reduced the number and severity of vasomotor symptoms and improved urogenital symptoms , compared with placebo . The E2 vaginal ring was well tolerated OBJECTIVE We studied the efficacy , safety , and acceptability of an estradiol-releasing ( 6.5 to 9.5 micrograms per 24 hours ) silicone vaginal ring ( Estring ) in postmenopausal women with symptoms and signs of urogenital aging during a treatment period of 1 year . STUDY DESIGN The study was open with blind analysis of vaginal cytologic testing . In addition to gynecologic examination , subjective symptoms were assessed and vaginal pH and urinary sample s ( for bacteriuria ) were obtained before insertion of Estring . This procedure was repeated every 3 months up to 1 year 's treatment , together with requests concerning acceptability and adverse experiences . At inclusion and end of Estring treatment , vaginal smears for evaluation of cytologic results were obtained . RESULTS Estring induced a high maturation value in the vaginal mucosa and restored vaginal pH to levels normality seen in fertile women ( < 5.5 ) . For most variables a 90 % responder rate ( proportion of cured and improved patients ) was found after 3 months and up to 1 year regarding subjective symptoms and objective signs of vaginal mucosal atrophy .  Twenty-eight ( 20 % ) of 136 women , withdrew from the study , 8 ( 6 % ) of them because of adverse events .  Three women reported vaginal bleeding , none associated with malignancy or endometrial proliferation . Ten ( 7 % ) reported vaginal irritation , and in two cases vaginal ulcers were found . About 90 % did not remove the ring during any of the 3-month treatment periods , and 78 % used the four consecutive rings continuously up to 1 year . The ring was given a strong preference ( p < 0.001 ) by patients with previous experience of other administration forms . CONCLUSION Estring represents a safe , highly effective , and very well-accepted administration form for long-term treatment of urogenital disorders caused by estrogen deficiency in postmenopausal women The objective of this study was to evaluate the efficacy of flaxseed meal and flaxseed extract in reducing climacteric symptoms of menopausal women . Ninety menopausal women were r and omly distributed into three study groups : group I received 1 g per day of flaxseed extract containing at least 100 mg of secoisolariciresinol diglucoside ( SDG ) , group II received 90 g per day of flaxseed meal containing at least 270 mg of SDG , and group III received 1 g per day of collagen ( placebo group ) . Subjects were assessed for menopausal symptoms by the Kupperman index at the beginning and at the end of the 6 months of treatment . Subjects were also assessed for endometrial thickness and vaginal cytology . The Kupperman index values at the beginning and end of the treatments were analyzed using the paired t-test . Both the flaxseed extract ( P=.007 ) and the flaxseed meal ( P=.005 ) were effective in reducing the menopausal symptoms when compared with the placebo control ( P=.082 ) . Alternatively , the changes in Kupperman index were also computed and su bmi tted to analysis of variance . In this case , no significant differences were found ( P=.084 ) although the data indicate a decreasing tendency for the Kupperman index by both the flaxseed extract and the flaxseed meal groups . Neither the flaxseed extract nor the flaxseed meal exerted clinical ly important estrogenic effects on the vaginal epithelium or endometrium as revealed by the absence of changes in the blood levels of follicle stimulating hormone and estradiol , as well as in the endometrial thickness , and vaginal epithelial maturation value . No serious adverse events related to the treatments were reported . Although the results of the present study do not allow an unequivocal conclusion about the action of flaxseed on the menopausal symptoms , they suggest that it could be premature to conclude that no such action exists . Clearly the matter still deserves further experimental attention OBJECTIVE Our purpose was to study the efficacy , safety , and acceptability of a new estradiol-releasing ( 6.5 to 9.5 micrograms per 24 hours ) silicone rubber vaginal ring compared with Ovesterin 0.5 mg estriol vaginal pessaries . STUDY DESIGN Gynecologic clinical status , vaginal pH , cytologic characteristics , and occurrence of bacteriuria were determined before starting and after 3 and 12 weeks of treatment in 146 postmenopausal women . RESULTS Both treatments alleviated the subjective and objective symptoms of estrogen deficiency excellently , and both were equally effective at restoring the vaginal pH to levels normally seen in fertile women ( < 5.5 ) . Vaginal cytologic studies showed a significant difference in maturation value in favor of the estradiol-releasing silicone rubber vaginal ring , as measured by the pathologist 's assessment of the proliferation of the vaginal mucosa . A total of 77 % of users were classified as responders , compared with 39 % in the pessary group . Both treatments were well accepted . The administration of the pessary was associated with a significantly higher ( p < 0.001 ) incidence of discomfort than that of the ring , which was given better ( p < 0.001 ) rating by the patients at the 12-week visit . A strong preference ( p < 0.001 ) for the ring was shown by patients with previous experience with pessaries . CONCLUSION Treatment of urogenital symptoms in postmenopausal women with an estradiol-releasing vaginal ring is shown to be an effective and safe method , exhibiting advantages over treatment with estriol vaginal pessaries Background : Most of the women suffer from vaginal atrophy and dryness , and therefore , efficient and safe treatment is needed to improve vaginal lubrication . Vitamin D has several important functions which may be effective in proliferation and repair of the epithelial tissue . This study aim ed to evaluate the effect of vitamin D vaginal suppositories on maturation index , pH , and dryness in postmenopausal women . Material s and Methods : Women were enrolled in this double-blind clinical trial , in whom menopause occurred at least one year ago . Those women who had an abnormal Papanicolaou smear , had undergone hormonal treatment , or have had vaginal infection in the previous year were excluded . Forty-four women who found eligible were r and omized into two equal groups , the treatment and control groups , which received vitamin D and placebo vaginal suppository daily for 8 weeks , respectively . Vaginal pH and maturation value were measured at the beginning and end of the study . Pain , dryness , and paleness were assessed before treatment and at the end of the 2 , 4 , and 8 weeks of treatment . Results : In the treatment group , the number ( Mean ± SD ) of superficial cells increased ( 69.76 ± 12.4 ) and vaginal pH decreased ( 1.42 ± 0.67 ) significantly compared to the control group after 56 days . The mean pain significantly reduced after 8 weeks in the treatment group ( 1.23 ± 0.53 ) compared to the control group 1.95 ± 0.74 ( P < 0.001 ) . The mean of dryness and paleness reduced significantly in the treatment group versus control at 56 days . Conclusions : Vitamin D is effective in improving the maturation index and decreased the pH and dryness of the vaginal atrophy due to menopause Aims The major aims of the study were to compare the safety of a continuous low-dose estradiol-releasing vaginal ring ( ESTring ) to that of a vaginal estradiol tablet ( Vagifem ® ) on the endometrium and the relief of subjective symptoms and signs of urogenital estrogen deficiency .  Quality of life and acceptability of treatment delivery were also assessed . Study design A prospect i ve , r and omized study in which women were assigned in a 2 : 1 ratio to ESTring and Vagifem  and followed for 12 months . The primary endpoint was endometrial safety , based on the results of ultrasound measurement of endometrial thickness and a progestogen challenge test at baseline and week 48 . Efficacy was determined by subjective assessment of urogenital estrogen deficiency symptoms at baseline and weeks 3 , 12 , 24 , 36 and 48 and assessment of signs of vaginal epithelial atrophy by the clinician at baseline , 12 and 48 weeks . In addition , pelvic floor strength , vaginal cytological evaluation and pH , bacteruria and patient acceptability were assessed . Quality of life was assessed using a menopause-specific quality -of-life question naire and a 2-day bladder diary at baseline and 12 and 48 weeks . The comparability of the two groups was assessed using ANOVA , χ2 or Fisher 's exact tests . Results A total of 126 women were r and omized to ESTring and 59 to Vagifem . There was no statistical difference between the groups in the alleviation of symptoms and signs of urogenital estrogen deficiency . Maturation indices increased in both groups , from generally atrophic at baseline to proliferative or highly proliferative at 48 weeks . After 48 weeks of treatment , there was no statistically significant difference in endometrial thickness between the two groups . A statistically smaller proportion of bleeding/spotting occurred in the ESTring group ( n = 0 ) compared to the Vagifem users ( n = 4 ) . Estradiol and total estrone serum levels increased during treatment in both groups but remained within the normal postmenopausal range . General health status in both groups was unchanged but the urogenital component of health burden was significantly improved in both groups . Bladder diary variables showed no differences between treatment groups . Conclusion Equivalent endometrial safety and efficacy in the relief of the symptoms and signs of urogenital estrogen deficiency were demonstrated for the 12 months ' use of a low-dose estradiol-releasing vaginal ring and a vaginal estradiol tablet OBJECTIVE The aim of this study was to explore the effect of a defined formula of Chinese medicinal herbs , GengNianAn ( GNA , also called menopausal symptom-relieving formula ) formula in relieving menopausal symptoms in ovariectomized women . DESIGN A double-blind r and omized placebo-controlled trial . METHOD Between May 2003 and June 2006 , 69 ovariectomized Chinese women were recruited to complete 12 weeks of intervention with either a defined formula of GNA ( n = 36 ) or placebo ( n = 33 ) taken twice daily as a beverage .  Clinical symptoms were assessed by the modified Kupperman scale . The levels of venous blood serum follicle stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , estradiol ( E(2 ) ) , and the maturation index ( MI ) of vaginal epithelial cells were respectively measured . RESULTS There existed significant differences between the two groups in the total Kupperman scoring , MI of vaginal exfoliative cells , and the levels of FSH , LH , and E(2 ) after treatment ( P < .05 ) . CONCLUSION Chinese herbs may be a useful alternative treatment for ovariectomized women suffering from menopausal symptoms , who are unable or do not want to receive hormone replacement therapy ( HRT ) Objective : The objective of this study was to evaluate the efficacy and safety of three doses of estradiol gel 0.1 % ( Divigel , a novel formulation consisting of 1 mg estradiol per 1 g transdermal gel ) to reduce the frequency and severity of vasomotor symptoms and signs of vulvar and vaginal atrophy associated with menopause . Design : A total of 488 postmenopausal women were evaluated in a 12-week study comparing placebo with estradiol gel 0.1 % at doses of 1.0 , 0.5 , and 0.25 mg/day , with estimated daily deliveries of 0.027 , 0.009 , and 0.003 mg of estradiol , respectively . Primary endpoints were the change from baseline in daily frequency and severity of moderate to severe vasomotor symptoms . Change from baseline in the signs of vulvar and vaginal atrophy ( vaginal pH and percentage of superficial cells ) was also assessed . Results : Treatment with estradiol gel 0.1 % showed statistically significant reductions in frequency and severity of vasomotor symptoms from baseline compared with placebo as early as Week 2 that were maintained throughout treatment . Signs of vulvar and vaginal atrophy were also significantly improved from baseline with all three doses of estradiol gel 0.1 % compared with placebo . Conclusions : Low-dose transdermal estradiol gel 0.1 % is an effective treatment for relief of vasomotor symptoms , as well as signs of vulvar and vaginal atrophy , associated with menopause . Estradiol gel 0.1 % offers multiple dosing options to individualize patient therapy , including the lowest available effective dose ( 0.25 mg estradiol , delivering 0.003 mg/d estradiol ) to treat the vasomotor symptoms of menopause BACKGROUND Relief of climacteric symptoms is currently the main role of hormone therapy . However , vaginal bleeding complicating this therapy is among the leading causes for its early discontinuation . OBJECTIVES To assess the effect of a vaginal ring delivering estradiol and progesterone in postmenopausal women and to determine whether continuous administration can relieve climacteric symptoms , produce an acceptable pattern of vaginal bleeding and control endometrial proliferation . METHODS Twenty-nine postmenopausal women with an intact uterus were studied . All had climacteric symptoms . The vaginal rings contained 0.36 g estradiol and either 3.6 g progesterone ( high dose progesterone ) or 1.8 g ( low dose progesterone ) , and were kept in place for 4 - 6 months . Serum progesterone , estradiol and estrone were measured and endometrial thickness determined . All women kept a daily diary of bleeding/spotting and completed a question naire on climacteric symptoms at monthly intervals . The low dose progesterone group comprised 14 women and the high dose progesterone group 15 women . RESULTS A total of 18 patients ( 9 in each group ) completed the study .  Mean levels of estradiol , estrone and progesterone were at their peak after 2 to 4 weeks . All rings were effective in alleviating vasomotor symptoms , although there was evidence of " escape from effect " in month 6 . Endometrial thickness increased in 6 of the 29 women but biopsy in each case showed no evidence of hyperplasia . Of the 18 women who completed the study , 5 had amenorrhea throughout , 7 had amenorrhea after 3 months , and the remainder had one or two bleeding episodes after 3 months . Therapy was discontinued in 11 women . CONCLUSIONS A vaginal ring delivering estradiol and progesterone controlled climacteric symptoms , prevented endometrial proliferation , and provided an acceptable bleeding pattern . It should be viewed as a possible alternative for short-term estrogen-progesterone therapy Objectives To compare the effect of micro-dose transdermal estradiol and placebo on the incidence and severity of menopausal symptoms and well-being in postmenopausal Asian women with vasomotor symptoms . Design Multicenter , double-blind , r and omized , placebo-controlled study . Results Of 165 subjects r and omized to estradiol 0.014 mg/day or placebo for 12 weeks , 80 per group were included in the analysis . Groups were comparable at baseline , although time since menopause was slightly shorter in the estradiol group . There was a greater reduction in mean weekly hot flushes at week 12 in the estradiol group ( 55 % ) than the placebo group ( 40 % ; p < 0.01 ) , which was evident by week 4 . A similar pattern was seen for moderate and severe hot flushes ( −58 % vs. −39 % , respectively ) . Reductions were statistically significant at weeks 4 , 8 , and 12 . Vaginal pH fell significantly in the estradiol group by week 4 and then remained stable throughout the treatment period , but there were no significant changes in the placebo group . Vaginal maturation value increased more in the estradiol than the placebo group ( p < 0.001 ) . Few subjects had vaginal bleeding or spotting . Quality of life improved similarly in both groups . Urogenital symptoms improved considerably from baseline in both treatment groups , with no significant differences . Eight subjects experienced treatment-related adverse events ( seven in the estradiol group ) . Conclusions In Asian women , micro-dose estradiol was significantly superior to placebo in improving vasomotor symptoms . The bleeding profile was comparable with that of placebo . Micro-dose estradiol was safe and well tolerated in Asian women OBJECTIVE : To evaluate the efficacy of two vaginal doses of estradiol ( E2 ) compared with placebo in the treatment of atrophic vaginitis . METHODS : In a multi-center , r and omized , double-blind , parallel-group study , 230 postmenopausal women received treatment with 25 mcg or 10 mcg E2 or placebo for 12 weeks . Efficacy was measured through composite score of three vaginal symptoms and grading of vaginal health . Additional analyses included maturation of vaginal and urethral mucosa . Safety assessment s included endometrial biopsy , adverse events , changes in laboratory tests , and physical examinations . After 12 weeks of treatment , all patients were switched to the open-label extension and received treatment with 25 mcg E2 up to week 52 . RESULTS : Vaginal tablets with 25 mcg and 10 mcg E2 showed significant ( P<.001 ) improvement in composite score of vaginal health . Other results with 10 mcg E2 were not entirely consistent with those for 25 mcg E2 . Over 12 weeks , both active treatments result ed in greater decreases in vaginal pH than placebo . There were no significant differences between the 25 mcg and 10 mcg E2 groups in terms of improvements in maturation value or composite score of three vaginal symptoms . The efficacy was maintained to week 52 with 25 mcg E2 . CONCLUSION : Vaginal tablets with 25 mcg and 10 mcg E2 provided relief of vaginal symptoms , improved urogenital atrophy , decreased vaginal pH , and increased maturation of the vaginal and urethral epithelium . Those improvements were greater with 25 mcg than with 10 mcg E2 . Both doses were effective in the treatment of atrophic vaginitis . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00465192 and NCT00464971 LEVEL OF EVIDENCE : OBJECTIVE : To evaluate the efficacy of ultra – low-dose 10-microgram 17&bgr;-estradiol ( E2 ) vaginal tablets for treatment of  vaginal atrophy .  METHODS : Postmenopausal women ( N=309 ) were r and omly assigned to 10-microgram E2 or placebo vaginal tablets for 52 weeks in a multicenter , double-blind study . Primary efficacy endpoints included change from baseline to week 12 in vaginal cytology , vaginal pH , and most bothersome urogenital symptoms score . Grading of vaginal health was a secondary efficacy assessment . Safety assessment s included endometrial biopsy , physical and gynecologic examinations , and recording adverse events . RESULTS : At week 12 , the change from baseline for 10 micrograms E2 compared with placebo demonstrated significant improvement in vaginal Maturation Index ( proportion of parabasal cells : –37 % compared with –9 % ; superficial cells : 13 % compared with 4 % ; intermediate cells : 24 % compared with 5 % ; P<.001 for each ) , Maturation Value ( 25.0 compared with 6.5 , P<.001 ) , grading of vaginal health ( –0.91 compared with –0.51 , P<.001 ) , vaginal pH grade ( –1.3 compared with –0.4 , P<.001 ) , and most bothersome symptoms score ( –1.23 compared with –0.87 , P=.003 ) . For each component of vaginal Maturation Index , vaginal Maturation Value , grading of vaginal health , and vaginal pH , treatment effects were statistically different from placebo after 2 weeks of treatment . For most bothersome symptoms , treatment effect became apparent after 4 weeks and reached statistical significance at week 8 of therapy . All treatment effects were statistically significant at week 52 . There were no major safety findings regarding physical , gynecologic , or laboratory assessment s. CONCLUSION : After 12 weeks of treatment , an ultra – low-dose 10-microgram E2 vaginal tablet , compared with placebo , demonstrated significant improvement for the primary endpoints : vaginal cytology and pH and most bothersome urogenital symptoms score . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , http:// clinical trials.gov , NCT00108849 LEVEL OF EVIDENCE : In post-menopausal period vulvo-vaginal atrophy (VVA)-related symptoms may seriously affect women 's quality of life . Hormonal replacement therapy effectively relieves these symptoms but it is not always safe or accepted , and a non-hormonal treatment is often needed instead . Over a period of 12 weeks , we tested the effect of a twice-a-week vulvo-vaginal application of a hyaluronic acid , AC collagen , isoflavones and vitamins-based cream ( Perilei Pausa ® ) on 35 women in post-menopausal period , reporting VVA-related symptoms . After 12 weeks of treatment with Perilei Pausa ® a significant improvement in vaginal dryness , vulvo-vaginal itching , dyspareunia ( P < 0.001 ) , dysuria ( P = 0.02 ) , nocturia ( P = 0.009 ) and pollakiuria ( P = 0.005 ) was reported by the women . Colposcopical score assessing the intensity of atrophic colpitis , cervico-vaginal paleness and petechiae was also reduced ( P = 0.037 , P = 0.016 and P = 0.032 , respectively ) . No significant difference in terms of maturation value of cervico-vaginal epithelium was observed . In conclusion , Perilei Pausa ® may represent an effective and safe alternative treatment of symptomatic VVA in post-menopausal women OBJECTIVES We assessed the effects of the discontinuation of long-st and ing transdermal estrogen replacement therapy ( > 4 years ) and substitution of this treatment by calcium or raloxifene on the vaginal epithelium and climateric symptoms in a study population of osteoporotic women . METHODS A total of 136 women ( mean age 55.5 years ) were r and omized to calcium ( 500 mg elemental calcium , 400 IU Vitamin D3 ) ( n=40 ) , raloxifene ( 60 mg/day ) ( n=48 ) , or estrogen patches ( 3.9 mg estradiol ) and progesterone ( 100 mg/day ) ( n=48 ) . Treatment was given for 1 year . The vaginal maturation value ( VMV ) , serum estradiol levels , and climateric symptoms using a 12-item modification of the SF-36 quality of life question naire were evaluated at baseline and at 6 and 12 months . RESULTS At 6 months , mean VMV decreased significantly ( P<0.001 ) in the calcium ( -51.8 % ) and raloxifene ( -18.6 % ) groups compared with baseline and the estrogen/progesterone group . At 12 months , significant decreases of mean VMV in the calcium ( -38.7 % ) and raloxifene groups ( -32 % ) ( P<0.001 ) were also observed . Serum estradiol levels and changes of VMV correlated significantly at 6 months ( rho=0.361 , P<0.01 ) and at 12 months ( rho=0.269 , P<0.035 ) . A significantly higher number of patients complained of hot flushes and palpitations in the calcium and raloxifene groups than in the estrogen/progesterone group . Raloxifene-treated women reported a significantly higher number of adverse events at 6 months compared to the other treatment groups . CONCLUSIONS Withdrawal and change of long-st and ing transdermal hormone replacement therapy by treatment with calcium or raloxifene result ed in worsening of vaginal atrophy assessed by the VMV , although it was not clinical ly perceived by the patients . However , increases in dyspareunia and urinary leaks were reported . Menopausal complaints related to vasomotor symptoms worsened in the calcium- and raloxifene-treated groups and persisted throughout the study period OBJECTIVES To compare the effects of estradiol vaginal tablet with conjugated estrogen cream on urogenital symptoms , vaginal health index , vaginal cytology , endometrial thickness , and plasma estradiol level in postmenopausal women . METHODS Fifty-three women with urogenital symptoms were r and omized to local vaginal treatment of 25 microg estradiol tablet or 1 g of conjugated estrogen cream for 12 weeks . They were assessed for urogenital symptoms , vaginal health index , vaginal cytology , endometrial thickness and estradiol level . RESULTS Forty-eight women completed the treatment . Both groups showed improvement of urogenital symptoms , vaginal health index , and vaginal cytology after the first 4 weeks of treatment . Conjugated estrogen cream showed superior efficacy in alleviating vaginal dryness and dyspareunia . Two cases of endometrial proliferation were noted . CONCLUSIONS Estradiol vaginal tablet and conjugated estrogen cream were effective in treating urogenital symptoms , the restoration of normal vaginal epithelium and reduction of vaginal pH in postmenopausal women . However , 2 cases of endometrial proliferation were noted INTRODUCTION Many postmenopausal women who are on hormone replacement therapy discontinue medications due to vaginal bleeding .  Tibolone , a synthetic steroid , has minimal stimulatory effect on the endometrium . The aim of this study was to assess the effects of continuous HRT regimen and tibolone on the onset of vaginal bleeding and vaginal maturation value . MATERIAL S AND METHODS A total of 150 healthy women in postmenopausal period were r and omly enrolled in this controlled clinical trial . Patients were r and omly allocated into three groups , and were followed for six months . The first 50 women received 2.5 mg tibolone plus a Cal+D tablet ( 500 mg Calcium and 200 IU vitamin D ) daily , the second 50 women received 0.625 mg conjugated equine estrogen and 2.5 mg medroxyprogesterone acetate ( CEE/MPA ) plus one Cal+D tablet daily , and the remaining 50 received only one Cal+D tablet per day and served as the control group . Symptoms were recorded using a question naire that assessed vaginal bleeding or spotting , vaginal dryness and intention to continue the medications . Vaginal maturation value was assessed by examining vaginal smears before and after the treatment . The results for the three groups were analyzed using statistical methods . RESULTS In comparison with the control group , CEE/MPA and tibolone increased vaginal maturation value and decreased the frequency of vaginal dryness ( p < 0.01 ) . Women in tibolone group were more likely to continue the treatment regimen than those in the CEE/MPA or the control groups ( p < 0.01 ) . CONCLUSION Tibolone can serve as an appropriate choice for HRT as it has low rates of vaginal bleeding/ spotting episodes and high acceptance rate in postmenopausal women Objective : Vaginal atrophy is a common chronic condition among postmenopausal women that can affect their quality of life . Recent studies have evaluated new treatment alternatives for vaginal atrophy ; however , few therapeutic options have been thoroughly evaluated . This study aim ed to compare the effectiveness and adverse effects of estrogen , testosterone , polyacrylic acid , and placebo lubricant for the treatment of postmenopausal women with vaginal atrophy . Methods : We conducted a r and omized clinical trial with 80 postmenopausal women aged between 40 and 70 years who were being followed up at the Menopause Clinic of CAISM UNICAMP between November 2011 and January 2013 . Women were r and omly assigned to topical vaginal treatment with estrogen , testosterone , polyacrylic acid , and placebo lubricant , three times a week for 12 weeks . We used the vaginal maturation index , pH , vaginal health score , vaginal flora , laboratory tests , and ultrasound to evaluate changes of vaginal atrophy at baseline and after 6 and 12 weeks of treatment . Results : After a 12-week treatment with topical estrogen and testosterone compared with the lubricant , an increased percentage of participants had vaginal pH less than 5 , increased vaginal score , and an increase in the number of lactobacilli . Treatment with topical estrogen improved the vaginal maturation index and showed increased levels of estradiol in three women . No changes were observed in the endometrial evaluation of all treatment groups . Conclusions : After a 12-week treatment with testosterone and estrogen compared with placebo lubrication , there was a significant improvement in vaginal trophism in postmenopausal women with vaginal atrophy Objectives : The efficacy and safety of 25‐μg 17&bgr;‐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 , result ing from estrogen deficiency . Design : In a multicenter , open‐label , r and omized , 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 17&bgr;‐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 result ed in greater patient acceptance and lower withdrawal rates compared with vaginal cream therapy . ( Menopause 2000;7:156‐161 . © 2000 , The North American Menopause Society . Objectives : To evaluate the efficacy and safety of different doses of 17&bgr;‐estradiol for the treatment of vasomotor and vulvovaginal symptoms . Design : This was a r and omized , double‐blind , multicenter , parallel‐group study . One hundred forty‐five subjects , including naturally postmenopausal women aged 40‐60 ( who had not experienced menses for at least 12 months ) , women who had undergone hysterectomy , and women aged 25‐60 who had undergone bilateral oophorectomy with or without hysterectomy were studied . Either placebo or 17&bgr;‐estradiol ( 1 mg or 0.5 mg ) was given orally every day for 12 weeks , and vasomotor symptoms and vaginal epithelial cytology were evaluated . Results : There were significant differences between placebo and the active treatments in the percentage change from baseline in the number of hot flushes ( all hot flushes , 1 mg vs. placebo , p < 0.001 ; 0.5 mg vs. placebo , p = 0.007 ) , with a more substantial proportion of subjects responding in the 1‐mg group ( mean change in mean number of hot flushes of 83.2 % ) . Both doses were also more effective than placebo in increasing the proportion of mature vaginal cells ( end‐of‐treatment mean values of 0 % , 78.5 % , and 21.5 % for parabasal , intermediate , and superficial cells , respectively , in the 1‐mg group ; mean values of 0.3 % , 80.8 % , and 18.9 % in the 0.5‐mg group ; and mean values of 15.2 % , 74.7 % , and 10.2 % in the placebo group ) . The proportion of subjects reporting no vaginal dryness was greatest in the 1‐mg group ( mean percentage of days without dryness of 86.1 % at weeks 9‐12 ) . Conclusions : For the relief of vasomotor and vulvovaginal symptoms , 17&bgr;‐estradiol 1 mg is effective and has an excellent safety profile . ( Menopause 2000;7:310‐317 . © 2000 , The North American Menopause Society . OBJECTIVE : To investigate safety and efficacy and identify the lowest effective dose of a new transdermal estradiol ( E2 ) gel for relief of menopausal symptoms in a population of postmenopausal women . METHODS : This study was a r and omized , double-blind , placebo-controlled , multicenter , parallel-group study . Postmenopausal women with at least 60 hot flushes per week applied 0.87 g/d ( n=136 ) , 1.7 g/d ( n=142 ) , or 2.6 g/d ( n=69 ) E2 gel or placebo gel ( n=137 ) topically for 12 weeks . The changes from baseline in hot flush frequency and severity at 4 and 12 weeks and changes from baseline in vaginal atrophy symptoms at 12 weeks were examined . RESULTS : With increasing E2 doses , mean trough serum E2 increased from 17 to 29 pg/mL. By weeks 3–5 , E2 gel reduced moderate-to-severe hot flush rate by at least seven hot flushes per day ( P<.001 ) and reduced the severity score ( P<.01 ) . The numbers needed to treat for benefit for an 80 % and 100 % decrease in hot flush number were 3.2 and 6.3 for the 0.87-g/d group and 1.3 and 2.3 for the 2.6-g/d group . At week 12 , vaginal pH was more acidic and vaginal maturation index more mature compared with placebo ( P<.001 ) . The lowest dose improved most bothersome vulvovaginal atrophy symptoms ( P<.05 ) . Estradiol gel was well tolerated at the site of application and produced no unexpected adverse effects . The 0.87 g/d dose produced fewest adverse events . CONCLUSION : The 0.87 g/d dose of this new transdermal E2 gel , which delivers an estimated 0.0125 mg E2 daily , delivered the lowest effective dose for treatment of vasomotor symptoms and vulvovaginal atrophy in a population of postmenopausal women . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00391417 LEVEL OF EVIDENCE : CONTEXT Investigating the adverse effects of oral hormone replacement therapy ( HRT ) , the clinical effectiveness of alternative combinations and route of administrations . AIM To compare the effects of intranasal and transdermal 17 beta-estradiol combined with vaginal progesterone on vasomotor symptoms and vaginal cytology . SETTING S AND DESIGN A 12-week , prospect i ve , r and omized comparative study was conducted between July 2005 and September 2006 . MATERIAL S AND METHODS Eighty postmenopausal women aged between 42 - 57 years , who had scores of > or = 1.7 on the menopause rating scale-I ( MRS-I ) items " 1 - 6 " , were r and omly assigned to receive intranasal ( 300 microg/day , n = 40 ) or transdermal ( 50 microg/day , n = 40 ) 17 beta-estradiol continuously . All patients also received a vaginal progesterone gel twice weekly . Vasomotor symptoms were evaluated at weeks 0 , 4 , 8 and 12 . Vaginal maturation index ( VMI ) was evaluated at weeks 0 and 12 of the study . STATISTICAL ANALYSES The Mann-Whitney U and the Wilcoxon tests were used . P < 0.05 was regarded as significant . RESULTS Thirty-two women in the intranasal and 29 women in the transdermal group completed the study . The total score of the MRS , the sum-scores of Factor 1 " HOT FLUSHES " and Factor 2 " PSYCHE " significantly decreased in both groups at week 4 . Factor 3 " ATROPHY " scores significantly decreased only in the transdermal group at week 12 . The VMI showed no changes within and between the two groups at the end of the study . CONCLUSION Intranasal and transdermal 17beta-estradiol combined with vaginal progesterone gel as a continuous HRT caused a similar decrease in vasomotor symptoms but did not have any significant effect on VMI after 12 weeks of treatment in this study population CONTEXT Pelvic organ prolapse ( POP ) increases in prevalence with age ; recurrence after surgical repair is common . OBJECTIVE The objective of the study was to determine the effects of local estrogen treatment on connective tissue synthesis and breakdown in the vaginal wall of postmenopausal women planning surgical repair of POP . DESIGN This was a r and omized trial . SETTING The study was conducted at an academic tertiary medical center . PATIENTS OR OTHER PARTICIPANTS Postmenopausal women with a uterus and symptomatic anterior and /or apical prolapse at stage 2 or greater participated in the study . INTERVENTION Estrogen ( Premarin ) or placebo cream for 6 weeks preoperatively was the intervention . MAIN OUTCOME MEASURES Full-thickness anterior apical vaginal wall biopsies were obtained at the time of hysterectomy and analyzed for mucosa and muscularis thickness , connective tissue synthesis , and degradation . Serum levels of estrone and 17β-estradiol were analyzed at baseline and the day of surgery using highly sensitive liquid chromatography-t and em mass spectrometry . RESULTS Fifteen women per group ( n = 30 total ) were r and omized ; 13 per group underwent surgery . Among drug-adherent participants ( n = 8 estrogen , n = 13 placebo ) , epithelial and muscularis thickness was increased 1.8- and 2.7-fold ( P = .002 and P = .088 , respectively ) by estrogen . Collagen types 1α1 and 1α2 mRNA increased 6.0- and 1.8-fold in the vaginal muscularis ( P < .05 for both ) ; collagen type Ia protein increased 9-fold in the muscularis ( P = .012 ) , whereas collagen III was not changed significantly . MMP-12 ( human macrophage elastase ) mRNA was suppressed in the vaginal mucosa from estrogen-treated participants ( P = .011 ) , and matrix metalloprotease-9 activity was decreased 6-fold in the mucosa and 4-fold in the muscularis ( P = .02 ) . Consistent with menopausal norms , serum estrone and 17β-estradiol were low and did not differ among the two groups . CONCLUSIONS Vaginal estrogen application for 6 weeks preoperatively increased synthesis of mature collagen , decreased degradative enzyme activity , and increased thickness of the vaginal wall , suggesting this intervention improves both the substrate for suture placement at the time of surgical repair and maintenance of connective tissue integrity of the pelvic floor
Although the level of evidence for the effects of vitamin D on vaginal health is low in our study , we concluded that vitamin D may improve the vaginal health of women , especially during menopause
Menopause is associated with the onset of climacteric symptoms due to low estradiol levels , which may cause insufficient maturation of the vaginal mucosa .
Vitamin D may regulate the growth and differentiation of cells that are adversely affected due to low estradiol levels , thereby restoring vaginal health .
The objective of this systematic review , the first on this subject , was to investigate the effect of vitamin D on the  vaginal health of menopausal women .