Change In Endometrial Thickness Research Articles

Опыт применения гидролизата плаценты у женщин с климактерическим синдромом в перименопаузе

This article presents the results of randomized, blind, placebo-controlled prospective study in parallel groups. 40 premenopausal women with symptoms of climacteric syndrome, menstrual disordersand FSH level more than 20 mIu/ml, were recruited and randomized into 2 groups: 20 women (group 1) used placenta extract Melsmon (Japan), 2 ml (100 mg), subcutaneously, every 2nd day for 2 weeks, then 2 time a week (30 injections for 4 months in total). 20 patients (group 2) were included in the placebo group (2 ml subcutaneously, in similar regimen). After 4 months of treatment the significant decrease of modified Kupperman menopausal index, decrease of time required tofall asleep and night time awakenings number, as far as increasing of sleep duration and significant improvement of general health self-assessment were registered in both groups. The improvement of psycho-emotional symptomsand skin condition after intervention was reported only in the 1st group. 32% of women used placental extract and 5% patients from placebo group reported about menstrual episodes after period of amenorrhea, without any significant changes in endometrial thickness. Study limitations: because of the small sample size and limited observation period, more long-term trials are needed.

The efficacy of intrauterine instillation of granulocyte colony-stimulating factor in infertile women with a thin endometrium: A pilot study.

ObjectiveThe study aimed to investigate the efficacy of intrauterine instillation of granulocyte colony-stimulating factor (G-CSF) on the day of ovulation triggering or oocyte retrieval in infertile women with a thin endometrium.MethodsFifty women whose endometrial thickness (EMT) was ≤8 mm at the time of triggering during at least one previous in vitro fertilization (IVF) cycle and an index IVF cycle were selected. On the day of triggering (n=12) or oocyte retrieval (n=38), 300 µg of G-CSF was instilled into the uterine cavity.ResultsIn the 50 index IVF cycles, the mean EMT was 7.2±0.6 mm on the triggering day and increased to 8.5±1.5 mm on the embryo transfer day (p<0.001). The overall clinical pregnancy rate was 22.0%, the implantation rate was 15.9%, and the ongoing pregnancy rate was 20%. The clinical pregnancy rate (41.7% vs. 15.8%), the implantation rate (26.7% vs. 11.7%), and the ongoing pregnancy rate (41.7% vs. 13.2%) were higher when G-CSF was instilled on the triggering day than when it was instilled on the retrieval day, although this tendency was likewise not statistically significant. Aspects of the stimulation process and mean changes in EMT were similar in women who became pregnant and women who did not.ConclusionIntrauterine instillation of G-CSF enhanced endometrial development and resulted in an acceptable pregnancy rate. Instillation of G-CSF on the triggering day showed better outcomes. G-CSF instillation should be considered as a strategy for inducing endometrial growth and good pregnancy results in infertile women with a thin endometrium.

Operative hysteroscopy for treatment of intrauterine pathologies does not interfere with later endometrial development in patients undergoing in vitro fertilization.

Operative hysteroscopy procedure is extensively used for the treatment of intrauterine abnormalities that can potentially cause infertility. To date, there are little data addressing the effect of operative hysteroscopy that applies electrical current for excision and its subsequent effect on endometrial thickness. This study was aimed to assess the effect of thermal resection used in operative hysteroscopy on endometrial thickness and on fertility outcome in women undergoing in vitro fertilization (IVF). A retrospective study conducted at Hadassah-Hebrew University Medical Center, a tertiary referral center. Included were IVF women who underwent an operative hysteroscopy throughout the years 2000-2010 for intrauterine pathologies. Throughout the years 2000-2010, 41 IVF women who underwent an operative hysteroscopy using electric current between their 82 IVF cycles were studied. The mean age of women at the time of the intervention was 37.1 years (36.7 and 37.5 at the IVF cycles before and after intervention, respectively). The maximal endometrial thickness before operative hysteroscopy was 10.7 mm compared to 9.5 mm after all procedures (P < 0.001). Excluding polypectomy cases (n = 24) the endometrial thickness was 9.9 mm before vs. 9.1 mm after operative hysteroscopy (P < 0.001). The clinical pregnancy rate was 19.5 % before as compared to 24.4 % after operative hysteroscopy (NS). The take home baby rate (THBR), however, was significantly increased following operative hysteroscopy for all indications from 2.4 to 12.2 % (P < 0.05). Despite the small change in endometrial thickness, our results indicate that using electric current is safe to treat intrauterine pathologies.

Analysis of the Result of Korean Medicine Treatment for Female Subfertility Using Herbal Medicine, Acupuncture and Moxibustion Treatment

Objectives: To report on the result of infertility treatment with Korean medicine in clinical settings. Methods: This study was single arm, retrospective observational study. Analysis of the medical records on thirty four infertile women who were treated by acupuncture, moxibustion, herbal medicine(Jokyungjongoktang-gagambang, Sutaehwan-gagambang). Pregnancy rate(PR) and Live birth rate(LBR) were analyzed as the primary outcomes. Changes of AMH, FSH, LH, E2, P4, endometrial thickness, fat mass, and BMI were also analyzed as the secondary outcomes. Results: A total of 34 patients were treated in the traditional Korean medical clinic. Nine patients were dropped, and 25 subjects completed the final examination at the end of this treatment schedule. Five of 25 subjects conceived during treatment, reaching 20% PR and LBR was also 20%. Except for FSH level, the results of the remaining outcome measures, including LFT, showed no significant changes. No serious adverse event has been reported. Conclusion: Although no significant changes in bio-markers were observed, complex treatment using Korean medicine has shown effectiveness on womens infertility. In addition, the safety of the treatment has been verified.

Treatment of menopausal symptoms with three low-dose continuous sequential 17β-estradiol/progesterone parenteral monthly formulations using novel non-polymeric microsphere technology

Objective: To analyze the short-term efficacy and safety over menopausal symptoms of three low-dose continuous sequential 17β-estradiol (E)/progesterone (P) parental monthly formulations using novel non-polymeric microspheres.Methods: This was a multicenter, randomized, single blinded study in which peri- and postmenopausal women were assigned to receive a monthly intramuscular injection of 0.5 mg E + 15 mg P (Group A, n = 34), 1 mg E + 20 mg P (Group B, n = 24) or 1 mg E + 30 mg P (Group C, n = 26) for 6 months. Primary efficacy endpoints included mean change in the frequency and severity of hot flushes and the effect over urogenital atrophy symptoms at 3 and 6 months. Safety variables included changes in the rate of amenorrhea, endometrial thickness and histopathology, and local and systemic adverse events.Results: Compared to baseline at month 6, the three treatment schemes significantly decreased the rate of urogenital atrophy symptoms and the frequency (mean number per day) and severity (mean number graded as moderate and severe per month) of hot flushes. No differences in studied efficacy parameters were observed between studied groups at baseline or at the end of the study. For all groups the most frequent adverse event was pain at the injection site; however they were all rated as mild. At the end of the study peri- and postmenopausal women displayed no significant changes in endometrial thickness or histopathology in all treated groups. The rate of amenorrhea at the end of the study decreased for all studied groups yet was less evident among postmenopausal women as compared to perimenopausal ones.Conclusions: The three low-dose continuous sequential intramuscular monthly treatments of E/P using novel microsphere technology were effective at reducing menopausal symptoms at short-term with a low rate of adverse events. More long-term and comparative research is warranted to support our positive findings.

English

OBJECTIVE: To evaluate the efficacy and safety of ormeloxifene in the medical management of dysfunctional uterine bleeding. DESIGN AND SETTING: A descriptive observational study was conducted on women with dysfunctional uterine bleeding, who attended to out - patient department of Obstetrics & Gynaecology in a National Institute Of Medical Science Medical College, shobha nagar, Jaipur (Rajsthan). MATERIAL AND METHOD: 54 patients with dysfunctional uterine bleeding were recruited for the study. Ormeloxifene 60 mg twice a week for 3 months from first day of periods and once a week for next 3 months was given. Mean blood loss (MBL) was assessed using pictorial blood loss assessment chart (PBAC). And subjectively by a visual analog scale (VAS).Ultrasonography (USG) for endometrial thickness and blood hemoglobin levels were done as baseline and at 1, 3 and 6 months of treatment. Side-effects of the drug were recorded. Changes in PBAC scoring, endometrial thickness (ET) and hemoglobin levels (Hb) were analyzed by student's paired 't' tests using SPSS 17.0 version. p value ≤ 0.05 was taken as significant. RESULT: The mean pretreatment MBL (PBAC score) was 343.13 (140-765), which reduced to 222.22 (80-398) at 1 months and 90.0 (0-340) at 3 months with treatment.By end of 6 months, the mean PBAC score was 68.84 (0-320). There was a significant reduction in MBL in patients on ormeloxifene (p-value ≤ 0.001).The rise in haemoglobin and decrease in ET,in women on ormeloxifene was also satistically significant(p value<o.oo1).Out of 54 patients,46 womens with menorrhagia were recruited in study. Three (6.52%) patients had no response, four (8.7%) patients were lost to follow-up. During the one year study period, 1(2.17) of the patients underwent hysterectomy.The most common side effect reorted was amenorrhea (28.26%). CONCLUSION: Ormeloxifene is very effective in improving all the parameters of blood loss in abnormal uterine bleeding including the no. of days of bleeding, no. of pads soiled and the passage of clots. Ormeloxifene has a good patient acceptability and compliance due to its minimal side effects, low cost and simple dosage schedule.

Can Melatonin Protect the Endometrium from the Adverse Effects of Caerulein?

We investigated the effects of a caerulein-induced acute pancreatitis (AP) on uterus and possible uterine protective effects of melatonin administration. Twenty-eight animals were divided into four groups: (1) control group (n = 7); (2) melatonin group (n = 7); (3) caerulein group (n = 7); (4) melatonin + caerulein group (n = 7). AP was induced by 4 intraperitoneal injection of caerulein given hourly (50 μg/kg) into young female animals. Melatonin (20 mg/kg) was given via intraperitoneal injection 30 min prior to the induction of AP. The rats were sacrificed by decapitation 12 h after the last injection of caerulein and their uterus were taken for histopathological evaluation. Mean body weight and uterine wet weight was recorded. The H-Score method was used to score the degree of histological changes of endo-myometrium edema, hemorrhage, necrosis, leucocyte infiltration, endometrial proliferation and endometrial thickness. There was no significant difference in the mean body weight observed after treatment in each group. The uterine wet weight differences between the control and caerulein given rats were significant (P<0.01). The endometrial thickness, edema, hemorrhage, necrosis and leucocyte infiltration of the caerulein group was significantly higher than the control and melatonin groups (P<0.01). It was observed that preteratment with melatonin normalized histological abnormalities and significantly reduced uterine wet weight as compared with the caerulein only group. Melatonin application may play an important role in the prophylaxis of uterine endometrium arising from adverse effects of caerulein.

Evaluation of a Levonorgestrel-Releasing Intrauterine System for Treating Endometrial Hyperplasia in Patients with Polycystic Ovary Syndrome

Objective: To evaluate the use of a levonorgestrel-releasing intrauterine system (LNG-IUS) for treating endometrial hyperplasia in patients with polycystic ovary syndrome (PCOS). Methods: LNG-IUSs were inserted in 60 PCOS patients with simple (40 cases), irregular (12 cases), or complex (8 cases) endometrial hyperplasia. Follow-ups were performed at 3, 6, 12, and 24 months after insertion. At each time point, changes in menstruation, hemoglobin level, and endometrial thickness and pathology were recorded. Menstrual changes were assessed with the Pictorial Blood Assessment Chart. Hemoglobin levels were measured by the Blood Routine Test. Endometrial thickness was determined by transvaginal ultrasound. Endometrial pathology was defined as simple, irregular, or complex endometrial hyperplasia by a pathologist after curettage. Outcomes at each time point were compared to baseline (pre-insertion) measurements by Student's t test or ANOVA (for multiple comparisons) with the post hoc Dunnett's test. Differences with a p < 0.05 were considered statistically significant. Results: At all time points after LNG-IUS insertion and in all patients, menstrual blood loss was decreased and hemoglobin level was increased significantly compared to pre-insertion levels. The endometrial thickness was significantly reduced in all groups after 12 months. Most patients showed transformation of the endometrial pathology, with complete disappearance of simple and irregular cases of endometrial hyperplasia and a decreased number of complex endometrial hyperplasia cases. Conclusions: LNG-IUS is an effective, safe, nonsurgical, and atraumatic approach with few side effects for the treatment of endometrial hyperplasia in patients with PCOS.

Endometrial Safety of Ospemifene and the Ability of Transvaginal Ultrasonography to Detect Small Changes in Endometrial Thickness

INTRODUCTION: Ospemifene is a nonestrogen with tissue selective agonist and antagonist effects recently approved for treatment of moderate to severe dyspareunia, a symptom of vulvovaginal atrophy resulting from menopause. The known increase in endometrial hyperplasia and carcinoma associated with unopposed systemic estrogen therapies warranted vigilance with regard to endometrial safety. Discussed here are the modalities to best establish endometrial safety in the context of the randomized controlled clinical trials of oral ospemifene at 60 mg per day compared with placebo in postmenopausal women exposed up to 52 weeks. METHODS: Six phase 2 and 3 clinical trials compared ospemifene at 60 mg per day with placebo. RESULTS: Endometrial safety was evaluated in 851 women exposed to ospemifene at 60 mg per day. Endometrial biopsies, vaginal bleeding, and transvaginal ultrasound scans for thickness and lesions were used. Change in endometrial thickness was significantly greater than placebo at 12 months (0.8±1.5 mm; P<.001); however, endometrial thickening of greater than 5 mm at the last visit demonstrated no statistically significant increase. Small endometrial thickness increases or decreases were not reproducible at different time points. Vaginal bleeding or spotting was reported in 1.2% of women with a uterus receiving ospemifene compared with 0.9% on placebo. There were no carcinomas, one case of simple hyperplasia without atypia (0.3%), and less than 1.0% active proliferation. CONCLUSION: The ospemifene endometrial profile, including histology and ultrasonography results for a maximum of 1 year of daily oral treatment, appears more consistent with the selective estrogen receptor modulator raloxifene than with steroidal estrogen. Histology, transvaginal ultrasonography greater than 5 mm, and symptoms of vaginal bleeding were helpful in discerning endometrial safety.

Study of Efficacy and Safety of Ormeloxifene in the Management of Dysfunctional Menorrhagia

ABSTRACTObjectiveTo assess the efficacy and safety of ormeloxifene in the medical management of dysfunctional menorrhagia.MethodologyFifty women with menorrhagia were recruited for the study. Ormeloxifene 60 mg twice a week for 3 months from first day of periods and once a week for next 3 months was given. Mean blood loss (MBL) was assessed using pictorial blood loss assessment chart (PBAC). Ultrasonography (USG) and blood hemoglobin levels were done as baseline and at 2, 4 and 6 months of treatment. Side-effects of the drug were recorded. Changes in PBAC scoring, endometrial thickness (ET) and hemoglobin levels (Hb) were analyzed by student's paired ‘t’ tests using SPSS 17.0 version. p value . 0.05 was taken as significant.ResultsThe pretreatment PBAC score was 360, which reduced to 209.5 at 2 months, 88.7 at 4 months and 68.2 at 6 months of treatment, which was statistically significant (p-value . 0.001). The rise in hemoglobin and decrease in ET, in women on ormeloxifene was also statistically significant (p-value . 0.001).ConclusionOrmeloxifene is an effective and safe therapeutic option for the medical management of menorrhagia.How to cite this articleGupta U, Shrivastava K, Katiyar G, Arif A, Gupta NK. Study of Efficacy and Safety of Ormeloxifene in the Management of Dysfunctional Menorrhagia. J South Asian Feder Menopause Soc 2014;2(1):1-4.

A double blinded randomized controlled trial to compare Ormeloxifene and Norethisterone in the treatment of Dysfunctional Uterine Bleeding

Aims: To compare the safety and efficacy of ormeloxifene and norethisterone in treatment of dysfunctional uterine bleeding as measured by decrease in menstrual blood loss using pictorial blood assessment chart. To assess the percentage change in haemoglobin and endometrial thickness before and after treatment. To assess the subjective improvement in life style as evaluated by a five point Likert scale. Methods: A double blinded randomized control trial was conducted on patients attending gynaecology OPD with complaints of menorrhagia with following inclusion criteria women between 18 and 51 years of age, absence of coagulopathies and any pelvic pathology, not taking any drug affecting menstruation, no hormonal therapy in previous three months and normal renal function. Findings and Interpretation: The menstrual blood loss was observed to decrease by 19.31% at end of two months, 30.74% at the end of four months and 43.25% at end of six months in case of norethisterone and 20.72% at the end of two months, 43.37% at end of four months and 59.50% at the end of six months in case of Ormeloxifene. There was an increase in haemoglobin percentage in both the groups and it was significantly better in case of Ormeloxifene. PBAC score and endometrial thickness improvement was better in case of ormeloxifene compared to norethisterone. The side effects were similar in both the cases except for follicular cyst which was seen in Ormeloxifene group. I. Introduction A woman can expect roughly 400 menstrual cycles during her reproductive lifespan, and it is estimated that up to 20% of women will have excessive menstrual blood loss. Although age of menopause has remained the same over this century, the magnitude of menstrual disorders has increased, likely because of shortened breast-feeding intervals, fewer pregnancies per woman, higher frequency of permanent sterilization, and later age of conception. Dysfunctional uterine bleeding is a diagnosis of exclusion when organic, systemic and pelvic pathology all have been ruled out. Once a diagnosis has been reached with the aid of history, examination, haematological and endocrine investigations, and dilatation and curettage when appropriate, medical treatment is the usual first line approach. The treatment options for dysfunctional uterine bleeding are diverse, which can be finally tailored to cater the needs of patients of different socioeconomic background, different age groups and different reproductive needs. Treatment options range from offering medical measures such as cyclooxygenase inhibitors, tranexamic acid, hormonal agents and in cases not managed by medical therapy offering surgical management. Trials comparing the various modalities have flooded the literature but ambiguity still exists. Norethisterone is still the most frequently prescribed drug for dysfunctional uterine bleeding serving 38% of the patient population the reason being cost effectiveness and absence of side effects. Ormeloxifene (also known as centchroman) is one of the selective estrogen receptor modulators used primarily as a contraceptive, but it is also effective in dysfunctional uterine bleeding. We undertook the study to compare the safety and efficacy of the two drugs in dysfunctional uterine bleeding.

Effects of mifepristone on uterine leiomyoma in premenopausal women: a meta-analysis

To conduct a meta-analysis of the studies assessing the effects of mifepristone on the uterus, uterine leiomyoma, and leiomyoma-related symptoms in premenopausal women. Meta-analysis. Centers for reproductive care. Premenopausal women who suffered from leiomyoma. We identified all of the studies published before December 2012 that compared the status of patients with leiomyoma before and after treatment with mifepristone. Leiomyoma-related symptoms, uterine or leiomyoma volume, changes in endometrial thickness. A meta-analytic technique was used to study 11 randomized controlled trials involving 780 women with symptomatic uterine leiomyomas. The subjects received 2.5-25 mg/d of mifepristone for 3-6 months. Mifepristone could effectively reduce uterine and leiomyoma volume and alleviate leiomyoma symptoms, including hypermenorrhea, the mean menstrual blood loss, pelvic pain, pelvic pressure, anemia, and dysmenorrhea. There was no significant difference in the rate of atypical endometrial hyperplasia between the mifepristone treatment group and the placebo group. Mifepristone significantly reduced uterine and leiomyoma volume and alleviated leiomyoma-related symptoms. We recommend 2.5 mg of mifepristone administered daily for 3 or 6 months as the optimum clinical treatment for leiomyoma. There is insufficient evidence that mifepristone treatment led to atypical endometrial hyperplasia.

Effect of isoflavone soy protein supplementation on endometrial thickness, hyperplasia, and endometrial cancer risk in postmenopausal women

This study aims to determine whether long-term isoflavone soy protein (ISP) supplementation affects endometrial thickness and rates of endometrial hyperplasia and cancer in postmenopausal women. In this randomized, double-blind, placebo-controlled trial, 350 postmenopausal women aged 45 to 92 years were randomized to a total daily dose of 154 mg of ISP or a milk protein-matched placebo for a 3-year period. Women with a surgically absent uterus were excluded from the analysis (final study population, N = 224). The main outcome measures were as follows: mean change in endometrial thickness on transvaginal ultrasound from baseline until up to 36 months of follow-up and the incidence of endometrial sampling, endometrial hyperplasia, and endometrial cancer. A total of 666 visits among 224 participants were evaluated. Treatment groups did not significantly differ on the mean baseline or on-trial changes in endometrial thickness. Of the 103 placebo-treated participants, 7 (6.8%) underwent endometrial biopsy; 6 (85.7%) of these biopsies were benign. One woman in the placebo group was diagnosed with complex endometrial hyperplasia with atypia and underwent hysterectomy. The pathology result from this surgical operation was stage IB endometrial cancer. Of the 121 participants in the soy group, 9 (7.4%) underwent endometrial biopsy. The results were benign in all nine cases (100%). Although the rate of hyperplasia/malignancy was higher in the placebo group (14.3% vs 0%), the difference was not statistically significant. Three-year ISP supplementation has no effect on endometrial thickness or on the rates of endometrial hyperplasia and cancer in postmenopausal women.

Assessment of the safety of long-term bazedoxifene treatment on the reproductive tract in postmenopausal women with osteoporosis: Results of a 7-year, randomized, placebo-controlled, phase 3 study

ObjectiveTo evaluate the clinical safety of bazedoxifene (BZA) on the reproductive tract in postmenopausal women with osteoporosis over 7 years. Study designThis was a second, blinded, 2-year extension of a 3-year, randomized, double-blind, placebo (PBO)- and active-controlled phase 3 trial. In the core study, subjects were randomized to receive BZA 20 or 40mg, raloxifene 60mg, or PBO. During years 4–5, the raloxifene arm was discontinued and subjects receiving BZA 40mg were transitioned to BZA 20mg. Subjects continued to receive BZA 20mg or PBO during years 6–7. Main outcome measuresThe primary endpoint was the incidence of new vertebral fractures at 7 years (reported separately). Reproductive tract safety findings at 7 years are reported here. Endometrial thickness was assessed by transvaginal ultrasonography for subjects in the endometrial safety substudy. Adverse events (AEs) were recorded throughout the study. ResultsAt 7 years, the adjusted mean (±standard error) change in endometrial thickness was similar with BZA and PBO (−0.11±0.21 and 0.07±0.32mm, respectively). The incidence of endometrial hyperplasia was low (0.1% for both groups). BZA showed significantly lower rates than PBO of endometrial carcinoma (0.1% vs. 0.4%; P=0.020) and vaginitis (6.1% vs. 7.6%; P=0.035). There were more cases of ovarian carcinoma with BZA (n=4 [0.1%]) than PBO (n=0); the difference was not statistically significant. Rates of breast-related and other gynecologic AEs were similar among groups. ConclusionsBZA was associated with a favorable reproductive safety profile in postmenopausal women with osteoporosis over 7 years.

Abstract 152: Endometrial thickness and risk of sex hormone-related cancers in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Abstract Background: Higher endogenous circulating estrogen levels have been linked to elevated risk of breast and endometrial cancers among postmenopausal women, and may also increase risk of ovarian and colorectal cancers. In the endometrium, excess estrogen relative to progesterone produces a net proliferative stimulus, which may result in endometrial thickening. Previous studies have found that risk factors such as body mass index (BMI) and menopausal hormone use, that appear to operate through estrogenic mechanisms, are directly related to endometrial thickness. Therefore, we tested the hypothesis that endometrial thickness is associated with risk of several sex hormone-related cancers. Methods: Postmenopausal female participants, aged 55-74 years, enrolled at the Pittsburgh site of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial who were screened by transvaginal ultrasound and had known baseline endometrial thickness measurements were included for study (N=1,272). Serial endometrial thickness measurements were available for a subset of women at one (n=1,018), two (n=869) and three years (n=641) after baseline. We modeled endometrial thickness as a baseline measure, a time-varying covariate, and as a change in endometrial thickness since the most recent ultrasound. Cox proportional hazards regression, with age as the time metric, was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the association between endometrial thickness and cancer risk, adjusted for potential confounders. Results: This subcohort (N=1,272) included 91 breast, 14 endometrial, 10 ovarian and 17 colorectal cancers diagnosed after baseline. Median follow-up time was 12.5 years (range: 0.7-13.8 years). At the baseline screen, median endometrial thickness measures were 4.0 millimeters (mm) for breast, 4.5 mm for endometrial, 3.0 mm for ovarian and 4.0 mm for colorectal cancer cases compared to 3.0 mm among women who did not develop cancer. Baseline endometrial thickness, modeled continuously, was associated with risk of breast cancer (RR: 1.08, 95% CI 1.02, 1.14) and endometrial cancer (RR: 1.13, 95% CI 1.02, 1.25) in models adjusted for baseline BMI, hypertension, diabetes, uterine fibroids, marital status, and menopausal hormone use. Similar associations were noted when modeling endometrial thickness as a time-varying covariate [breast cancer (RR: 1.07, 95% CI 1.00, 1.15), endometrial cancer (RR: 1.13, 95% CI 1.00, 1.28)]. No significant association between endometrial thickness and risk of ovarian or colorectal cancer was observed. The change in endometrial thickness since the most recent ultrasound was not associated with cancer risk. Discussion: Our data suggest that transvaginal ultrasound assessments of endometrial thickness, even among asymptomatic women, may be useful in risk prediction of breast and endometrial cancer. Citation Format: Ashley S. Felix, Joel L. Weissfeld, Ruth M. Pfeiffer, Amanda Black, Mark E. Sherman, Louise A. Brinton. Endometrial thickness and risk of sex hormone-related cancers in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 152. doi:10.1158/1538-7445.AM2013-152

RETRACTED: Role of phyto-oestrogens in ovulation induction in women with polycystic ovarian syndrome

To study the role of a phyto-oestrogen, Cimicifuga racimosa extract (Klimadynon(®), Bionorica, Neumarkt i.d.OBf., Germany), in ovulation induction in women with polycystic ovarian syndrome (PCOS). Prospective randomized controlled trial in Minia University Hospital, Minia, Egypt. One hundred women with PCOS were allocated into one of two groups: one group (n=50) received clomiphene citrate 100mg daily for 5 days, and the other group (n=50) received C. racimosa 20mg daily for 10 days. Both groups received medication starting from the second day of the cycle for three consecutive cycles, during which changes in follicle-stimulating hormone (FSH), luteinizing hormone (LH), FSH/LH ratio, progesterone, endometrial thickness and pregnancy rate were measured. The groups were similar in terms of age, clinical presentation and hormonal levels before treatment. Following treatment, significant favourable changes in LH level and FSH/LH ratio (p=0.007 and 0.06, respectively) were seen in the Klimadynon group. In this group the progesterone level was higher from the first treatment cycle, indicating better ovulation (p=0.0001), and endometrial thickness was greater (p=0.0004). The pregnancy rate was higher in the Klimadynon group but the difference between the groups was not significant (p=0.1). Phyto-oestrogen can be used as an alternative to clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome.

Effective treatment of vaginal atrophy with isoflavone vaginal gel

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

The Effect of Isoflavone Soy Protein (ISP) Supplementation on Endometrial Thickness, Hyperplasia and Endometrial Cancer Risk in Postmenopausal Women: A Randomized Controlled Trial

Soy isoflavones are structurally similar to 17β-estradiol and possess selective estrogen receptor modulator (SERM)-like activity. In postmenopausal women, isoflavone soy protein (ISP) supplementation has been shown to have multiple health benefits, such as reduction of subclinical atherosclerosis when initiated within 5 years of menopause [1]. However, the effect of ISP supplementation on the endometrium has not been studied. To determine whether long term ISP supplementation affects endometrial thickness and rates of endometrial hyperplasia and cancer in postmenopausal women. In this randomized, double-blind, placebo-controlled trial, 350 postmenopausal women 45-92 years of age without diabetes and cardiovascular disease (CVD) were randomized to 2 evenly divided daily doses of 25 g soy protein containing a total of 154 mg of ISP or a milk protein matched placebo for a 3-year period. Participants with a surgically absent uterus were excluded from this analysis. For the remaining 222 participants, ultrasonographic and histopathologic characteristics of the endometrium were compared between intervention and control groups. Compliance with ISP supplementation was confirmed by plasma and urine isoflavone measurements. Endometrial thickness was measured by transvaginal ultrasound at baseline and at 18 and 30 months of follow-up, as well as at 36 months in some participants. The mean change of endometrial thickness from baseline was recorded and compared between treatment groups. Participants with endometrial thickness ≥5 mm and those with vaginal bleeding underwent endometrial biopsies. Incidences of endometrial sampling, endometrial hyperplasia and endometrial cancer were compared between groups. A total of 666 visits among 222 participants were evaluated. There was no statistically significant difference between groups in the baseline endometrial thickness or in changes of endometrial thickness over the trial follow-up (Table 1, p>0.8). Of the 101 placebo-treated participants, 7 (6.9%) underwent an endometrial biopsy; 6 (85.7%) of these biopsies were benign. Of these, 4 were benign, not otherwise specified, and 2 were atrophic. One placebo subject was diagnosed with atypical endometrial hyperplasia and underwent a hysterectomy. The pathology result from this surgery was Stage IB endometrial cancer. Of the 121 participants in the soy group, 9 (7.4%) underwent an endometrial biopsy. The results were benign in all 9 cases (100%). Of these, 5 were benign, not otherwise specified, 3 were atrophic, and 1 proliferative. Although the rate of hyperplasia / malignancy was higher in the placebo group (14.3% versus 0%), the difference was not statistically significant (Table 2). Three-year isoflavone soy protein (ISP) supplementation has no effect on endometrial thickness or on rates of endometrial hyperplasia and cancer in postmenopausal women.

Bioavailability and pharmacodynamics of two 10-mg estradiol valerate depot formulations following IM single dose administration in healthy postmenopausal volunteers

To establish the bioequivalence (BE) between two i.m. estradiol valerate (E2V) depot formulations, i.e., Estradiol-Depot 10 mg® (test) and Progynon Depot-10® (reference). To compare the effect of both treatments on the vaginal maturation index and on the increase of the endometrial thickness after administration of both formulations. A total of 24 postmenopausal females aged 54.7 ± 5.35 year (BMI 25.84 ± 1.98 kg/m2) completed this BE assessment. The investigation was planned and designed as a single center, openlabel, single dose, cross-over study including 2 periods with 2 treatments and 2 sequences. Baseline levels were obtained for all subjects. Single doses of 10-mg E2V of each product were administered and pharmacokinetics and pharmacodynamics were assessed over 2 weeks with a washout period of 4 weeks. A gas chromatographic-mass spectrometric method with negative chemical ionization and selected ion monitoring was applied, after validation, for the determination of estradiol (E2), estrone (E1) and internal standard estradiol-D4 derivatives. The cytology of the vaginal smear (parabasal, intermediate and superficial cells from lateral wall opposite tip of cervix) was assessed by investigation of ~ 200 cells. The vaginal maturation index (VMI) was calculated by the equation: VMI (%) = (superficial cells × 1) (%) + (intermediate cells × 0.5) (%). Endometrial thickness was measured by transvaginal ultrasonic scans and recorded in mm. The geometric means (Gmeans) of the measured values of Cmax and AUC0-t for E2 were 543.5 pg/ ml and 84,734 pg × h/ml for test and 505.7 pg/ml and 82,660 pg × h/ml for reference, whereas those for E1 were 219.0 pg/ml and 38,950 pg × h/ml for test and 204.9 pg/ml and 37,159 pg × h/ml for reference, respectively. The point estimates (PEs) of the Test/ Reference (T/R) mean ratios of the variables Cmax and AUC0-t for E2 (measured values) were 107.3% and 102.5%, respectively. The PEs of the T/R mean ratios of the variables Cmax and AUC0-t for E1 (measured values) were 106.9% and 105.0%, respectively. Median endometrial thickness increased in Period I from baseline levels of ~ 3 mm (Day -2) to ~ 7 mm (Day 21) after administration of both products without returning completely to baseline prior to the next administration. In Period II, median values of 7 mm were also reached (Day 21) after administration of both products. Median vaginal maturation indices increased in Period I from baseline levels of ranging from 45 - 60% (Day -2) to 86 - 94.5% (Day 21). In Period II maturation indices of ≥ 90% were calculated as baselines (Day -2) and these levels remained constant until the end of the assessment (Day 21) independently from the products. After 21 days of treatment, test and reference presented practically no differences in terms of their effects on endometrial thickness and vaginal maturation index. The 95% CIs for the T/R mean ratios of AUC0-t and Cmax for E2 and E1 fell within the acceptance limits of 80 - 125% and therefore bioequivalence could be demonstrated for both formulations. The changes in endometrial thickness and the vaginal maturation index indicated that the pharmacodynamic effect is pronounced already after the first administration and that the effect continued notably for longer time compared to the presence of E2 and E1 in plasma. A 4-week washout phase was insufficient to avoid residual pharmacological effects after the administration of both preparations.

A gradual increase of endometrial thickness from the day of hCG to the day of ET is predictive of pregnancy outcome in patients with a thin endometrium (< 8mm)

An adequate endometrial thickness is necessary for successful implantation. Numerous studies have demonstrated that thin endometrium on the day of hCG is associated with low pregnancy rates. This study was carried out to evaluate the relationship between a gradual increase of endometrial thickness from the day of hCG to the day of ET and pregnancy success and applied to the patients who have less than 8 mm of endometrial thickness on the day of hCG. A prospective study. One hundred two patients who have an endometrial thickness < 8 mm on the hCG day were examined and divided into two different groups by the changes of endometrial thickness. Group I belonged a gradual increase of endometrial thickness from the hCG day to the ET day and Group II with a slow decrease. Luteal phase was supported by 8% progesterone gel daily and 6∼8 mg/day oral E2. Among 102 patients, 46 patients showed a gradual increase of endometrial thickness (Group I) whereas 56 patients showed a slow decrease (Group II). Both groups were similar age, E2 levels on the hCG day, no. of retrieved oocytes and transferred embryos. Clinical PR and ongoing PR were significantly higher in Group I than Group II (P<0.01).Table 1Characteristics and pregnancy outcome.VariableGroup I(Increase)Group II(decrease)No. of patients4656Age36.3 ± 4.336.8 ± 4.6E2 level on the day of hCG(pg/ml)1213 ± 9951334 ± 1029No. of ET2.8 ± 0.72.9 ± 0.8Endometrial thickness(mm) On the hCG day7.8 ± 0.3a7.7 ± 0.3a On the OPU day8.6 ± 0.5b7.8 ± 0.4a On the ET day*9.8 ± 0.6c7.0 ± 0.3b Clinical PR(%)**71.719.6 Ongoing PR(%)**63.07.1Data expressed as means ± SD or % *P< 0.05, **<0.01 and a,b,c < 0.05. Open table in a new tab Data expressed as means ± SD or % *P< 0.05, **<0.01 and a,b,c < 0.05. If endometrial thickness of patients having a thin endometrium (<8 mm) on the day of hCG has gradually increased from the hCG day to the ET day, we would expect high pregnancy rate and ongoing pregnancy rate. Therefore, endometrial thickness on the ET day is important parameter than that on the hCG day in patients with a thin endometrium.