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
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 :
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 .