Vaginal Estradiol Research Articles

TEMPORARY REMOVAL: Effect of soy isoflavones on measures of estrogenicity: A systematic review and meta-analysis of randomized controlled trials

BackgroundDespite recommendations to increase plant food consumption for public and planetary health and the role that soy foods can play in plant-predominant diets, controversies around the effects of soy foods and especially soy isoflavones, are a barrier to their intake. Given their cardioprotective effects and ability to alleviate menopausal symptoms, addressing these concerns is particularly relevant to women. ObjectiveThis systematic review and meta-analysis of randomized controlled trials aimed to determine the effect of soy isoflavones on measures of estrogenicity in postmenopausal women. MethodsMEDLINE, Embase, and Cochrane Library were searched through August 2024 for randomized trials 3-months investigating soy isoflavones versus non-isoflavone controls in postmenopausal women. Outcomes included endometrial thickness (ET), vaginal maturation index (VMI), follicle-stimulating hormone (FSH), and estradiol. Independent authors extracted data and assessed risk of bias. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess certainty of evidence. ResultsWe included 40 trials (52 trial comparisons, n=3285) assessing the effect of a median reported dose of 75mg/day of soy isoflavones in substitution for non-isoflavone controls over a median of 24 weeks. Soy isoflavones had no statistically significant effect on any measure of estrogenicity; ET (mean difference, -0.22mm [95% confidence interval, -0.45, 0.01mm], PMD=0.059), VMI (2.31 [-2.14, 6.75], PMD=0.310), FSH (-0.02IU/L [-2.39, 2.35IU/L], PMD=0.987), and estradiol (1.61pmol/L [-1.17, 4.38pmol/L], PMD=0.256). The certainty of evidence was high-to-moderate for all outcomes. ConclusionsCurrent evidence suggests that soy isoflavones do not exhibit estrogenic effects compared to non-isoflavone controls on 4 measures of estrogenicity in postmenopausal women. This synthesis supports that soy isoflavones likely act as selective estrogen receptor modulators, differing clinically from the hormone estrogen. Addressing public health concerns may promote soy foods as high-quality plant protein sources with low environmental impact and cost, particularly benefiting postmenopausal women, and aligning with sustainable dietary patterns and guidelines. RegistrationPROSPERO (CRD42023439239)

Recurrent venous thromboembolism and vaginal estradiol in women with prior venous thromboembolism: A nested case-control study.

Whether vaginal estradiol use is associated with an increased risk of recurrent venous thromboembolism (VTE) in women with prior VTE is unknown. We sought to evaluate the association between vaginal estradiol use and recurrent VTE in women with prior VTE. We performed a nationwide nested case-control study among 44 024 women aged ≥45 years who developed a first VTE without a history of vaginal estrogen use prior to VTE diagnosis. Cases with recurrent VTE were matched 1:2 on birth year with controls using incidence density sampling. Exposure to vaginal estradiol tablets was categorized into current use (0-2 months before index), prior use (2-24 months before index) and past use (more than 24 months prior to index). We identified 5066 cases and 10 127 age-matched controls. In fully adjusted analysis vaginal estrogen was not associated with recurrent VTE with a hazard ratio of 0.75, p = .07 for current use, 0.83, p = .13 for prior use, and 1.24, p = .06 for past use. Use of vaginal estradiol tablets in women with prior VTE was not associated with an increased rate of recurrent VTE. Our study indicates that vaginal estradiol therapy is unlikely to increase risk of recurrent VTE in women with prior VTE.

Effect of High Serum Estradiol Levels and Duration of Vaginal Estradiol Administration on Reproductive Outcomes in Frozen-Thawed Embryo Transfer Cycles

Effect of High Serum Estradiol Levels and Duration of Vaginal Estradiol Administration on Reproductive Outcomes in Frozen-Thawed Embryo Transfer Cycles

Locally administered nanosuspension increases delivery of estradiol for the treatment of vaginal atrophy in mice.

Vaginal atrophy affects up to 57% of post-menopausal women, with symptoms ranging from vaginal burning to dysuria. Estradiol hormone replacement therapy may be prescribed to alleviate these symptoms, though many vaginal products have drawbacks including increased discharge and local tissue toxicity due to their hypertonic nature. Here, we describe the development and characterization of a Pluronic F127-coated estradiol nanosuspension (NS) formulation for improved vaginal estradiol delivery. We compare the pharmacokinetics to the clinical comparator vaginal cream (Estrace) and demonstrate increased delivery of estradiol to the vaginal tissue. We utilized ovariectomized (OVX) mice as a murine model of post-menopausal vaginal atrophy and demonstrated equivalent efficacy in vaginal re-epithelialization when dosed with either the estradiol NS or Estrace cream. Further, we demonstrate compatibility of the estradiol NS with vaginal bacteria in vitro. We demonstrate that a Pluronic F127-coated estradiol NS may be a viable option for the treatment of post-menopausal vaginal atrophy.

Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway

BackgroundIt is important to monitor the association between menopausal hormone therapy (HT) use and breast cancer (BC) risk with contemporary estimates, and specifically focus on HT types and new drugs.MethodsWe estimated hazard ratios (HR) of BC risk according to HT type, administration route and individual drugs, overall and stratified by body mass index (BMI), molecular subtype and detection mode, with non-HT use as reference.ResultsWe included 1,275,783 women, 45+ years, followed from 2004, for a median of 12.7 years. Oral oestrogen combined with daily progestin was associated with the highest risk of BC (HR 2.42, 95% confidence interval (CI) 2.31–2.54), with drug-specific HRs ranging from Cliovelle®: 1.63 (95% CI 1.35–1.96) to Kliogest®: 2.67 (2.37–3.00). Vaginal oestradiol was not associated with BC risk. HT use was more strongly associated with luminal A cancer (HR 1.97, 95% CI 1.86–2.09) than other molecular subtypes, and more strongly with interval (HR 2.00, 95% CI: 1.83–2.30) than screen-detected (HR 1.33, 95% CI 1.26–1.41) BC in women 50–71 years. HRs for HT use decreased with increasing BMI.ConclusionsThe use of oral and transdermal HT was associated with an increased risk of BC. The associations varied according to HT type, individual drugs, molecular subtype, detection mode and BMI.

Association between vaginal microbiota and vaginal inflammatory immune markers in postmenopausal women.

In premenopausal individuals, vaginal microbiota diversity and lack of Lactobacillus dominance are associated with greater mucosal inflammation, which is linked to a higher risk of cervical dysplasia and infections. It is not known if the association between the vaginal microbiota and inflammation is present after menopause, when the vaginal microbiota is generally higher-diversity and fewer people have Lactobacillus dominance. This is a post hoc analysis of a subset of postmenopausal individuals enrolled in a randomized trial for treatment of moderate-severe vulvovaginal discomfort that compared vaginal moisturizer, estradiol, or placebo. Vaginal fluid samples from 0, 4, and 12 weeks were characterized using 16S rRNA gene sequencing (microbiota) and MesoScale Discovery (vaginal fluid immune markers: IL-1b, IL-1a, IL-2, IL-6, IL-18, IL-10, IL-9, IL-13, IL-8, IP10, MIP1a, MIP1b, MIP3a). Global associations between cytokines and microbiota (assessed by relative abundance of individual taxa and Shannon index for alpha, or community, diversity) were explored, adjusting for treatment arm, using linear mixed models, principal component analysis, and Generalized Linear Mixed Model + Microbiome Regression-based Kernel Association Test (GLMM-MiRKAT). A total of 119 individuals with mean age of 61 years were included. At baseline, 29.5% of participants had a Lactobacillus -dominant vaginal microbiota. Across all timepoints, alpha diversity (Shannon index, P = 0.003) was highly associated with immune markers. Individual markers that were associated with Lactobacillus dominance were similar to those observed in premenopausal people: IL-10, IL-1b, IL-6, IL-8 (false discovery rate [FDR] < 0.01), IL-13 (FDR = 0.02), and IL-2 (FDR = 0.09). Over 12 weeks, change in alpha diversity was associated with change in cytokine concentration (Shannon, P = 0.018), with decreased proinflammatory cytokine concentrations observed with decreasing alpha diversity. In this cohort of postmenopausal individuals, Lactobacillus dominance and lower alpha diversity were associated with lower concentrations of inflammatory immune markers, as has been reported in premenopausal people. This suggests that after menopause lactobacilli continue to have beneficial effects on vaginal immune homeostasis, despite lower prevalence.

Vaginal estradiol tablets not associated with breast cancer

Vaginal estradiol tablets not associated with breast cancer

Association of vaginal oestradiol and the rate of breast cancer in Denmark: registry based, case-control study, nested in a nationwide cohort

ObjectiveTo estimate the rate of breast cancer associated with use of vaginal oestradiol tablets according to duration and intensity of their use.DesignRegistry based, case-control study, nested in a nationwide cohort.SettingBased...

Vaginal estradiol and hyaluronic acid in cervical preparation for office hysteroscopy in peri- and postmenopausal women

Vaginal estradiol and hyaluronic acid in cervical preparation for office hysteroscopy in peri- and postmenopausal women

Central nervous system tumours among users of vaginal oestradiol tablets: a nationwide population-based study.

It is currently unknown whether cumulative use of vaginal oestradiol is associated with development of meningioma and glioma. We conducted a nested case-control study within a nationwide cohort of Danish women followed from 2000 to 2018. The cohort consisted of 590,676 women aged 50-60 years at study start, without prior cancer diagnosis or use of systemic hormone therapy. Information on cumulative dose, duration, and intensity of vaginal oestradiol tablet use was assessed from filled prescriptions. Conditional logistic regression provided adjusted hazard ratios (HR) for the association between vaginal oestradiol use and diagnosis of meningioma or glioma. We identified 1,108 women with meningioma and 835 with glioma. Of these, 19.8% and 14.0% used vaginal oestradiol tablets, respectively. The HRs with ever use of vaginal oestradiol tablets was 1.14 (95% CI, 0.97-1.34) for meningioma and 0.90 (0.73-1.11) for glioma. The corresponding HRs for new users exclusively were 1.18 (0.99-1.40) for meningioma and 0.89 (0.71-1.13) for glioma. Intensity of vaginal oestradiol tablet use according to duration and user status yielded slightly elevated HRs for meningioma without an apparent dose-response pattern, while HRs of glioma were generally below unity. Among new users, the HR with high intensity of current or recent vaginal oestradiol tablet use for 2+ years was 1.66 (1.09-2.55) for meningioma and 0.77 (0.41-1.44) for glioma. Use of vaginal oestradiol tablets was associated with a slightly increased incidence of meningioma but not of glioma. Owing to the observational nature of the study, residual bias cannot be ruled out. This article is protected by copyright. All rights reserved.

Safety and serum estradiol levels in hormonal treatments for vulvovaginal atrophy in breast cancer survivors: A systematic review and meta-analysis.

e24049 Background: Vulvo-Vaginal Atrophy (VVA) or Genitourinary Syndrome of Menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing antiestrogen therapy. Despite being an option in refractory cases, the safety of hormonal treatment remains uncertain in this population. The aim of this study was to review the safety and serum estrogen levels of hormonal therapy in patients with BC history presenting with VVA symptoms. Methods: Pubmed, Embase, and Cochrane were searched for studies comparing different hormonal treatment options for VVA in breast cancer survivors. Statistical analysis was performed using a random effects model and heterogeneity using Cochran's Q-statistic and the I2 index. Results: We included 17 studies, of which 5 were randomized controlled trials (RCTs). Treatment modalities included in this study were topical vaginal estradiol and estriol preparations, vaginally applied testosterone, DHEA, and ospemifene. We found that, among patients treated with the estriol and estradiol preparations, there was an average increase of 7.67pg/ml (SMD 7.67 pg/mL; 95% CI -1.00, 16.35; p &lt; 0.001). Analysis of the testosterone group found temporary peaks of serum estradiol levels, but one study showed persistent elevation above normal postmenopausal levels. One study with prasterone revealed no elevation of serum estradiol concentration. One study with ospemifene demonstrated no increase in the risk of BC recurrence. Conclusions: In conclusion, among treatments available for BC survivors, low-dose vaginal estrogen showed the smallest changes in serum estradiol levels and had the most evidence, but safety remains unclear, especially for patients on aromatase inhibitors. Alternative treatments such as ospemifene need more data supporting safety and efficacy. These results suggest that concerns related to cancer recurrence should keep aiming for the lowest possible concentration.

Comparative Evaluation of Sildenafil Citrate and Estrogen as an Adjuvant Therapy for Treatment of Unexplained Infertility in Women.

Uterine blood flow determines endometrial thickness. This study examined how vaginal sildenafil citrate and estradiol valerate altered endometrial thickness, blood flow, and fertility in infertile women. This study observed 148 infertile women whose infertility was unexplained. Group 1 comprised 48 patients who received oral estradiol valerate (Cyclo-Progynova 2 mg/12 h white tablets) from day 6 till ovulation was initiated with clomiphene citrate. A number of 50 participants in group 2 received oral sildenafil (Respatio 20 mg/12 h film-coated tablets) for 5 days starting the day after their previous menstrual period and finishing on the day they ovulated with clomiphene citrate. Group 3 was the control group, with 50 patients receiving clomiphene citrate (Technovula 50 mg/12 h tablets) ovulation induction from the 2nd to 7th day of cycle. All patients had transvaginal ultrasounds to determine ovulation, follicle count, and fertility. Miscarriage, ectopic pregnancy, and multiple pregnancies were monitored for three months. The three groups' mean ETs differed statistically at p = 0.0004. A statistically significant difference was found between the three groups in terms of the number of follicles, with 69% of patients in group 1 having one and 31% having two or more, 76% of patients in group 2 having one and 24% having two or more, and 90% of patients in the control group having one and 10% having two or more (p = 0.038). The clinical pregnancy rates of the three groups were 58%, 46%, and 27%, respectively (p = 0.005). The distribution of all side effects was not statistically different between the three groups. It is possible to claim that adding oral estrogen to clomiphene citrate therapy as an adjuvant therapy can improve endometrial thickness and, as a result, increase the pregnancy rates in unexplained infertility compared to sildenafil, especially in cases where the infertility has lasted less than two years. Most people who take sildenafil end up with a mild headache.

Evaluation of Early Frozen Blastocyst Transfer in A True Natural Cycle Protocol in Comparison to A Hormone Replacement Protocol: A Single-Center Cohort Study.

Timing of frozen embryo transfer (FET) within a purported window of implantation is of increasing interest, and there is a paucity of evidence surrounding the transfer of frozen embryos early within these frozen embryo transfer protocols. This study aimed to evaluate whether live birth rates were equivalent after FET of blastocysts 4 days after luteinizing hormone (LH) surge in a true natural cycle protocol, compared to a hormone replacement (HR) protocol. Single-centre, retrospective cohort study involving patients undergoing autologous frozen blastocyst transfer from January 1st, 2013, to December 31st, 2016. Cycles were grouped according to their protocol: true natural cycle (hormonal detection of LH surge with FET scheduled four days later) versus HR cycle (luteal phase gonadotropin-releasing hormone agonist suppression, oral or vaginal estradiol and intramuscular progesterone starting five days before FET). A total of 850 cycles were included, 501 true natural cycles and 349 HR cycles. The primary outcome was the live birth rate, secondary outcomes included clinical pregnancy rate and miscarriage. Logbinomial regression models were performed adjusting for a priori selected variables. Adjusted resulted in live birth rates of 38.7 and 40.4%, [adjusted risk ratio (aRR): 0.96, 95% confidence interval (CI): 0.76-1.22, P=0.729] in the natural cycle and HR groups, respectively. The secondary outcome analyses did not demonstrate any statistically significant difference in the rate of positive human chorionic gonadotropin (hCG), clinical intrauterine pregnancy rate, or miscarriage rate. The timing of the FET four days after LH surge in a true natural cycle protocol results in equivalent live birth rates compared to a HR protocol. Results of this study suggest that the window of implantation within the natural cycle may be less finite than currently believed and further prospective studies evaluating the timing of frozen embryo transfer are warranted.

Agonist long protocol improves outcomes of vitrified-warmed embryo transfer in repeatedly thin endometrium

Research questionDoes follicular stimulation using human menopausal gonadotrophin (HMG) after pituitary down-regulation by a GnRH agonist improve endometrial thickness (EMT) and clinical outcomes of frozen-thawed embryo transfer (FET; using vitrified-warmed embryos) in women with thin endometrium after intensified oestrogen administration (IOA)? DesignThis was a retrospective study. A total of 627 patients attempted 683 FET cycles with at least one previous history of thin endometrium. None of the cycles reached over 7 mm EMT after using oral and vaginal oestradiol for more than 21 days (IOA protocol). A total of 129 cycles proceeded with FET, 305 cycles were cancelled, and 249 cycles involved administration of HMG following GnRH agonist pituitary down-regulation (GnRH agonist + HMG protocol) for further endometrial preparation. ResultsEMT became significantly greater (7.18 ± 1.14 mm versus 6.13 ± 0.63 mm, P < 0.001) using GnRH agonist + HMG compared with previous IOA cycles, but this was not related to serum oestrogen concentrations. A total of 213 cycles after the GnRH agonist + HMG protocol proceeded with FET, showing a significantly increased clinical pregnancy rate, implantation rate and live birth rate compared with those after IOA. ConclusionsThe GnRH agonist + HMG protocol for endometrial preparation in FET cycles improves EMT in women with a thin endometrium after IOA and showed significantly better clinical outcomes than IOA. The authors suggest that the GnRH agonist + HMG protocol should be used for EMT that is less than 7 mm after there has been no optimal response to IOA.

Association of Vaginal Estradiol Tablet With Serum Estrogen Levels in Women Who Are Postmenopausal

Half of women who are postmenopausal have genitourinary discomfort after menopause. Recommended therapies include low-dose vaginal estrogen. Individuals with a history of breast cancer or venous thromboembolism may have concerns about the safety of this intervention. To compare serum estrogen concentrations with the use of vaginal estrogen, 10 μg, tablet vs placebo in women who are postmenopausal. This is a secondary, post hoc analysis of data from a randomized clinical trial of treatment for moderate to severe genitourinary syndrome in women who are postmenopausal. The study was conducted at Kaiser Permanente Washington Health Research Institute and the University of Minnesota from April 11, 2016, to April 23, 2017. Measurements and data analysis were performed from November 3, 2020, to September 23, 2022. Participants were randomly assigned to vaginal estradiol tablet (10 μg/d for 2 weeks and then twice weekly) plus placebo gel (3 times weekly) or dual placebo for 12 weeks. In this post hoc analysis, baseline and week 12 serum estradiol, estrone, and sex hormone-binding globulin (SHBG) concentrations were measured by a chemiluminescent assay. Week 12 values of the 3 analytes were compared by baseline participant characteristics. Linear models compared week 12 estradiol concentrations between treatment groups, adjusted for baseline characteristics. A total of 174 women, mean (SD) age 61 (4) years, were included. Those in the estrogen group (n = 88) were more likely to have higher geometric mean (SD) week 12 serum estradiol concentrations (4.3 [2.2 pg/mL]) than those in the placebo group (n = 86) (3.5 [2.1] pg/mL) (P = .01). Adjusted for pretreatment hormone concentrations, age, clinical site, and body mass index, assignment to the estrogen vs placebo treatment group was significantly associated with higher week 12 estradiol concentrations (23.8% difference; 95% CI, 6.9%-43.3%). Most (121 of 174 [69.5%]) participants had enrollment serum estradiol concentrations higher than 2.7 pg/mL. Of women starting treatment at estradiol levels lower than or equal to 2.7 pg/mL, 38.1% (8 of 21) in the estrogen group and 34.4% (11 of 32) in the placebo group had estradiol concentrations higher than 2.7 pg/mL after 12 weeks of study participation (P = .78). Treatment assignment was not associated with week 12 estrone or SHBG concentrations. In this secondary analysis of a randomized clinical trial, a significant, although small, increase in serum estradiol levels was noted after 12 weeks of vaginal estrogen administration. The clinical relevance of this small increase is uncertain. ClinicalTrials.gov Identifier: NCT02516202.

Administration of Coumestrol and/or Dimethyl Sulfoxide Affects Vaginal Epithelium and Sex Hormones in Female Dog

Background: The overpopulation of free dogs represents a risk to public health in some countries. However, current strategies for its control are insufficient; it is convenient to devise new alternatives. Methods: To determine the effects of a single oral administration of coumestrol (COU) on vaginal epithelial cells, serum progesterone and estradiol levels and clinical parameters: periovulatory bitches received a biscuit that contained 600 µg COU/kg diluted in DMSO or with DMSO alone or without additives. Each group was subdivided into animals that had ovulated on day 0 and those that had not. Result: In animals that ovulated, COU did not affect hormonal profiles. In contrast, animals that did not ovulate showed lower circulating P4 concentrations on days 21 and 28 after treatment than the control group. Furthermore, COU reduced parabasal cells and increased superficial anucleate cells. COU and DMSO are estrogenic and their actions depend on the ovulatory status of the animals.

Impact of Topical Interventions on the Vaginal Microbiota and Metabolome in Postmenopausal Women

Postmenopausal women with genitourinary symptoms of menopause are often prescribed vaginal estradiol or moisturizer for symptom improvement, but the impact of these treatments on the local microenvironment is poorly understood. To compare changes in the vaginal microbiota, metabolome, and pH among women using low-dose vaginal estradiol tablet or low pH moisturizer gel for 12-weeks vs low pH placebo. This is a post hoc prespecified secondary analysis of a 12-week multicenter randomized clinical trial among postmenopausal women with moderate to severe genitourinary symptoms. Women were enrolled between April 2016 and February 2017; final follow-up visits occurred in April 2017. Data were analyzed from November 2018 to July 2021. Ten-μg vaginal estradiol plus placebo gel vs placebo tablet plus vaginal moisturizer vs dual placebo. The main outcome measures were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Of 302 postmenopausal women from the parent trial, 144 women (mean [SD] age, 61 [4] years) were included in this analysis. After 12 weeks, the microbiota was dominated with Lactobacillus and Bifidobacterium communities among 36 women (80%) in the estradiol group, compared with 16 women (36%) using moisturizer and 13 women (26%) using placebo (P < .001). The composition of vaginal fluid metabolites also varied after 12-weeks among women in the estradiol group with significant changes in 90 of 171 metabolites measured (53%) (P < .001), including an increase in lactate. The 12-week pH among women in the estradiol group was lower vs placebo (median [IQR] pH, 5 [4.5-6.0] vs 6 [5.5-7.0]; P = .005) but not the moisturizer group vs placebo (median [IQR] pH, 6 [5.5-6.5]; P = .28). There was a decrease in pH from baseline to 12-weeks within the moisturizer (median [IQR] pH, 7 [6.0-7.5] vs 6 [5.5-6.5]; P < .001) and placebo (median [IQR] pH, 7 [7.0-7.5] vs 6 [5.5-7.0]; P < .001) groups. Women with high-diversity bacterial communities at baseline exhibited greater median change in pH compared with women with low-diversity communities (median [IQR] change, -1 [-2 to -0.5] vs -0.3 [-1.1 to 0], P = .007). This secondary analysis of a randomized clinical trial found that use of vaginal estradiol tablets resulted in substantial changes in the vaginal microbiota and metabolome with a lowering in pH, particularly in women with high-diversity bacterial communities at baseline. Low pH moisturizer or placebo did not significantly impact the vaginal microbiota or metabolome despite lowering the vaginal pH. Estradiol use may offer additional genitourinary health benefits to postmenopausal women. ClinicalTrials.gov Identifier: NCT02516202.

Addition of dydrogesterone to vaginal progesterone and transfer postponement improve outcomes in patients with low progesterone levels in hormonally substituted cycles for frozen-thawed embryo transfer

Purpose: Adding dydrogesterone (DYD) to vaginal micronized progesterone (VMP) and postponing embryo transfer in order to improve outcomes in patients with low progesterone (P) levels in hormonally substituted cycles prior to frozen/thawed embryo transfer (FET). Methods: Endometrial preparation comprised sequential administration of vaginal estradiol until endometrial thickness reached 7 mm, followed by transdermal estradiol combined with 800 mg/day VMP. Our previous analysis of serum P levels on FET day showed that the optimal P level was &gt; 11 ng/mL for live birth. Serum P was measured on day1 (D1) following exogenous VMP introduction in the evening. When P levels were &gt; 11 ng/mL, FET was performed “in phase” on day-2, day-3, or day-5 depending on embryo stage at cryopreservation (n = 139 cycles). When P levels were &lt; 11 ng/mL, DYD 10 mg three times a day orally, was added to VMP and FET was postponed by one day (n = 237 cycles, 63%). The primary endpoint was the comparison of live birth rates (LBR) between the two groups. Results: Mean serum P level on D1 was 10.2 + 3.7 ng/mL. Characteristics of patients in both groups were similar for age, body mass index, endometrial thickness prior to P introduction, quality of transferred embryos, and embryo transfer stage. Regarding the primary endpoint, LBR was similar between the VMP+DYD group and the VMP group (26.1% vs. 27.3%, NS). Conclusion: These results suggest that adding DYD to VMP and postponing the transfer in patients with low P levels in hormonally substituted FET cycles might optimize outcomes.

A Comparative Study on the Effects of Vaginal Misoprostol and Vaginal Misoprostol Plus Estradiol on Labor Induction

Background: Cervical ripening is an important factor in predicting successful labor induction. In an unfavorable cervix, ripening should be done before induction. In this study, the effect of misoprostol and that of misoprostol plus estradiol on cervical ripening were compared. Methods: This randomized, double-blinded study included a total of 190 pregnant women who were identified for pregnancy termination due to maternal or fetal cause at 37 weeks with Bishop score of less than 4. The patients were assessed between April 2015 to April 2016 in two university hospitals at northeast Iran (Omol-Banin Hospital and Emam Reza Hospital, Mashhad). The patients who met the inclusion criteria were randomly assigned to two groups: the intervention group (Group A), who received 25 micrograms of vaginal misoprostol plus 50 micrograms of estradiol, and the control group (Group B), who received 25 micrograms of vaginal misoprostol only. Misoprostol was administered at 4-hour intervals until cervical ripening (Bishop score ? 8) or upon initiation of active phase in both the groups. The maximum dosage of misoprostol was three doses, whereas estradiol was administered only once. Results: In this study, the main causes of pregnancy termination were ROM and post-term. There was no significant statistical difference in the Bishop score between the two groups (P = 0.13). In addition, no significant difference was observed in the duration of time for cervical ripening (Bishop ? 8) between the two groups (P = 0.7). The duration between drug administration to the initiation of active phase and also from active phase to delivery showed no significant differences between the two groups (P = 0.49 and 0.24, respectively). There was also no significant difference in the delivery route (operative vaginal delivery or Cesarean section) (P = 0.2 and P = 0.91, respectively). Conclusion: From this study, the use of misoprostol plus estradiol did not improve cervical ripening or decrease the induction time. Further studies are recommended to investigate complementary results.

Efficacy of low-dose vaginal 17β-estradiol versus vaginal promestriene for vulvovaginal atrophy

Objective Vulvovaginal atrophy is frequent, can be bothersome and can impair quality of life in postmenopausal women. The main objective of this prospective, randomized study was to compare the acceptability of low-dose vaginal 17β-estradiol (estradiol) tablets and vaginal promestriene cream in postmenopausal women with moderate-to-severe symptomatic vulvovaginal atrophy. Methods Overall, 120 patients were randomized to receive estradiol or promestriene (n = 60 per group). Acceptability was assessed with a specific questionnaire. Symptom intensity, the Vaginal Health Index (VHI), vaginal pH and the Vaginal Maturation Index were also evaluated. Results Acceptability was higher for estradiol tablets. Compared to promestriene cream, hygiene and ease of use were greater after 4 weeks (p = 0.011 and p = 0.001, respectively) and after 12 weeks (p = 0.009 and p = 0.011, respectively). Reduction of symptom intensity was greater with estradiol. Both treatments improved the VHI and decreased vaginal pH. However, superficial cell percentages increased significantly (p < 0.001) with estradiol but not with promestriene (p = 0.241), with a statistically significant difference between means (p = 0.004). Conclusion Our results support the use of vaginal low-dose estradiol tablets as compared to vaginal promestriene cream for the management of moderate-to-severe symptomatic vulvovaginal atrophy in postmenopausal women. ClinicalTrials.gov Identifier NCT04232813