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Background: Polycystic ovary syndrome (PCOS) is an endocrine disease characterized by hyperandrogenism and hyperinsulinemia, followed by luteinizing hormone and follicle-stimulating hormone deficiency. PCOS conditions cause metabolic disorders that increase uric acid levels and malondialdehyde (MDA) levels. Animal models of PCOS have been used extensively in research to study the pathogenesis, clinical characteristics, and treatment of PCOS. Aim: This study aimed to identify the pathological mechanisms underlying renal dysfunction in PCOS by observing several parameters, including blood urea nitrogen (BUN), creatinine, uric acid, and renal MDA levels. Methods: This research was an experimentally designed study using a Wistar rat (Rattus norvegicus) as an animal model of PCOS which were divided into three groups: negative control group (n = 6), Testosterone propionate (TP) induction group (n = 6), and estradiol valerate (EV) induction group (n = 6). Results: According to statistical analysis it indicated that induction of TP and EV can increase blood uric acid levels in PCOS model rats (p < 0.05), TP induction can increase kidney BUN and MDA levels significantly (p < 0.05), However, the observation of creatinine levels did not show significant differences in all treatment groups (p > 0.05). Conclusion: Based on the results of this study, it can be concluded that the induction of animal models with TP can trigger significant renal damage compared to EV. [ABSTRACT FROM AUTHOR]

The main objective of this in vivo study was to investigate the effect of different low-level laser therapy (LLLT) doses on polycystic ovary syndrome (PCOS). In the present experimental study, a single dosage of estradiol valerate (EV) was administered to induce PCOS in female rats. After administration of the EV for induction of PCOS, rats were divided into 5 groups (n = 8/group): C group (animals that were not exposed to any form of procedure), PC group (no treatment following EV induction), L1 group (1 J/cm2 LLLT treatment following EV induction), L2 group (2 J/cm2 LLLT treatment following EV induction), L3 group (6 J/cm2 LLLT treatment following EV induction). The results indicated that no significant difference was found in the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and progesterone (P4) between the C and L2 groups (p < 0.05). Although the serum levels of testosterone (T) were significantly higher in the C group compared with other groups (p < 0.05), the L2 group was determined to be the closest to the C group. Additionally, the LH, FSH, and T receptor level of the L2 group was closest to the C group. In conclusion, a 2 J/cm2 dosage of LLLT (L2 group) can be considered the most potentially effective treatment of PCOS in the rat. However, more studies are needed to determine the optimal dose of LLLT for the treatment of PCOS. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Study Question: Does an estradiol-based combined oral contraceptive (COC) have a milder effect on the serum proteome than an ethinylestradiol (EE)-based COC or dienogest (DNG) only?Summary Answer: The changes in serum proteome were multifold after the use of a synthetic EE-based COC compared to natural estrogen COC or progestin-only preparation.What Is Known Already: EE-based COCs widely affect metabolism, inflammation, hepatic protein synthesis and blood coagulation. Studies comparing serum proteomes after the use of COCs containing EE and natural estrogens are lacking.Study Design, Size, Duration: This was a spin-off from a randomized, controlled, two-center clinical trial. Women (n = 59) were randomized to use either EE + DNG, estradiol valerate (EV) + DNG or DNG only continuously for 9 weeks.Participants/materials, Setting, Methods: Participants were healthy, young, white volunteer women. Serum samples were collected before and after 9 weeks of hormonal exposure. Samples from 44 women were available for analysis (EE + DNG n = 14, EV + DNG n = 16 and DNG only n = 14). Serum proteins were analyzed by quantitative, discovery-type label-free proteomics.Main Results and the Role Of Chance: Altogether, 446 proteins/protein families with two or more unique peptides were detected and quantified. The number of proteins/families that altered over the 9-week period within the study groups was 121 for EE + DNG and 5 for EV + DNG, while no changes were detected for DNG only. When alterations were compared between the groups, significant differences were detected for 63 proteins/protein families, of which 58 were between the EE + DNG and EV + DNG groups. The most affected functions during the use of EE + DNG were the complement system, acute phase response signaling, metabolism and the coagulation system. The results were validated by fetuin-B and cortisol-binding globulin ELISA and sex hormone-binding globulin immunoassay.Large Scale Data: Data are available via ProteomeXchange with identifiers PXD033617 (low abundance fraction) and PXD033618 (high abundance fraction).Limitations, Reasons For Caution: The power analysis of the trial was not based on the proteomic analysis of this spin-off study. In the future, targeted proteomic analysis with samples from another trial should be carried out in order to confirm the results.Wider Implications Of the Findings: The EE-based COC exerted a broader effect on the serum proteome than the EV-based COC or the DNG-only preparation. These results demonstrate that the effects of EE in COCs go far beyond the established endpoint markers of estrogen action, while the EV combination is closer to the progestin-only preparation. The study indicates that EV could provide a preferable option to EE in COCs in the future and signals a need for further studies comparing the clinical health outcomes of COCs containing EE and natural estrogens.Study Funding/competing Interest(s): Funding for this researcher-initiated study was obtained from the Helsinki University Hospital research funds, the Hospital District of Helsinki and Uusimaa, the Sigrid Juselius Foundation, the Academy of Finland, the Finnish Medical Association, the University of Oulu Graduate School, the Emil Aaltonen Foundation, the Swedish Cultural Foundation in Finland, the Novo Nordisk Foundation, Orion Research Foundation and the Northern Ostrobothnia Regional Fund. The funders had no role in study design, data collection and analysis, publishing decisions or manuscript preparation. T.P. has received honoraria for lectures, consultations and research grants from Exeltis, Gedeon Richter, MSD, Merck, Pfizer, Roche, Stragen and Mithra Pharmaceuticals. O.H. occasionally serves on advisory boards for Bayer AG and Gedeon Richter and has designed and lectured at educational events for these companies. The other authors have nothing to disclose. O.H. occasionally serves on advisory boards for Bayer AG and Gedeon Richter and has designed and lectured at educational events for these companies. The other authors have nothing to disclose.Trial Registration Number: ClinicalTrials.gov NCT02352090.Trial Registration Date: 27 January 2015.Date Of First Patient’s Enrolment: 1 April 2015. [ABSTRACT FROM AUTHOR]

Objectives: Ethinylestradiol (EE)-based combined oral contraceptives (COC) affect adrenal function by altering steroid and corticosteroid-binding globulin (CBG) synthesis that may contribute to adverse effects related to these drugs. The effects of COCs containing natural estrogens remain unclear. We compared the effects of COCs containing estradiol valerate (EV) and EE on cortisol and other adrenal steroid hormones.Study Design: A spin-off study of a randomized, open-label trial. Fifty-nine healthy women were allocated to groups that engaged in the continuous use of EV+dienogest (DNG), EE+DNG, or DNG only for 9 weeks. We measured changes in adrenal steroids, CBG, and the free cortisol index (FCI).Results: Treatment with EE+DNG increased total cortisol (mean increment 668 nmol/L, p < 0.001) and cortisone (10 nmol/L, p= 0.001) levels, whereas the change from the baseline was insignificant for the EV+DNG and DNG-only groups. Dehydroepiandrosterone sulfate decreased by 24% in the EE+DNG group but remained unchanged in the EV+DNG and DNG-only groups. Aldosterone and 17-hydroxyprogesterone levels did not differ between the groups. All preparations increased CBG, but the increase in the EE+DNG group (median increment 42 µg/mL, p < 0.001) was 9- and 49-fold higher than that in the EV+DNG and DNG-only groups, respectively. The FCI remained unchanged in all study groups, indicating that cortisol and CBG mainly increased in parallel, although some individuals demonstrated larger alterations in the cortisol-CBG balance.Conclusion: In COCs, EV had a milder effect on circulating CBG and adrenal steroid levels than EE; however, further research is necessary to determine the long-term effects.Trial Registration: ClinicalTrials.gov NCT02352090 IMPLICATIONS: EV-based COC had reduced effects on circulating CBG and adrenal steroids compared to EE, probably due to a lower hepatic impact. Whether the sensitization of the adrenals to ACTH varies according to COC contents and whether it relates to experienced side effects needs to be investigated. These results encourage further research and development of contraceptives containing natural estrogens. [ABSTRACT FROM AUTHOR]

Study design: Randomized trial. Objective: This study was designed to investigate the effects of different doses of estrogen on the expression of estrogen receptor (ER) in endometrial tissue and ovarian function in patients with unexplained recurrent spontaneous abortion (URSA). Methods: Eighty-eight patients with URSA in our outpatient department were randomly divided into three groups. They were treated with estradiol valerate (EV); standard dose of 4 mg/d (31 cases), high dose of 6 mg/d (27 cases) and 9 mg/d (30 cases). Progesterone was detected in the luteal phase, ovarian ovulation during follow-up treatment and the next month after drug withdrawal. ER expression in intima of EV 4 mg group, EV 6 mg group, and EV 9 mg group was detected by immunohistochemistry and PCR was performed before and 3 months after the treatment. Results: Anovulation of 88 URSA patients during hormone treatment was found as follows: 5 cases in the EV 4 mg group, 18 cases in the EV 6 mg group, 25 cases in the EV 9 mg group; Anovulation in the next month after drug withdrawal: 1 case in EV 4 mg group, 8 cases in EV 6 mg group, and 16 cases in EV 9 mg group. After stratified and grouped analysis, the expression of intimal ER in the EV 4 mg group, EV 6 mg, and EV 9 mg groups was significantly increased compared to before treatment in the 3 groups after treatment compared to before treatment (p <.05). There was no significant difference in ER expression between the three groups before and after treatment (p >.05). Conclusion: The higher the therapeutic dose of estrogen, the stronger the inhibition of ovarian ovulation, and the standard dose of estrogen has obvious advantages in increasing the expression of ER in intima. Limitation: 1) Insufficient sample size; 2) We need to increase the sampling time point to further observe the difference of estrogen in time effect, so as to obtain a more accurate action time of estrogen; 3) The longer-term effects of different doses of estrogen on intima were not studied, such as whether there are adverse pregnancy outcomes such as preterm birth, placental implantation, or premature exfoliation. [ABSTRACT FROM AUTHOR]

Introduction: Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E2 ] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin.Material and Methods: We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2-3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover).Clinical Trial Registration: NCT02352090.Results: Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change -24%, 95% confidence interval [CI] -32% to -15%; p < 0.01) and time to thrombin peak (-26%, 95% CI -37% to -16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%-67% vs +147%,95% CI 96%-198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%-38% vs +64%, 95% CI 51%-76%; p < 0.01). Median F1 + 2 levels remained unchanged with EV + DNG (p = 0.22) but increased within normal ranges with EE + DNG (from 152 pmol/L, 95% CI 127-206] pmol/L to 194 pmol/L, 95% CI 149-250 pmol/L, p = 0.04). The within-group change in D-dimer levels was not significant in any of the groups. DNG alone did not affect these biomarkers.Conclusions: Both in vitro and in vivo thrombin generation was lower after exposure to EV + DNG compared with EE + DNG. The lower thrombin generation measures after treatment with EV + DNG indicate less enhancement of coagulation potential and suggest that EV may be favorable to EE as a component of combined oral contraceptives. [ABSTRACT FROM AUTHOR]

Interoduction: One of the most well-known endocrinopathies in females in the period of reproduction is the Polycystic ovary syndrome (PCOS). PCOS is activated by the long-acting steroid, estradiol valerate (EV) that leads it to appear quickly due to metabolic and physiological abnormalities. It has been found that oxidative stress may lead to PCOS. Among the natural antioxidant products, pomegranate molasses (PM) is widely used. Objective: The goal of this work was to explore the possible protection of PM on EV induced PCOS in female adult albino rats. Materials and Methods: Forty normally cyclic female adult albino rats were separated into four groups (ten rats for each group); Group I: control group, Group II: pomegranate molesses treated group, Group III: estradiol valerate treated group and Group IV: estradiol valerate and pomegranate molesses treated group. After 6 weeks, cytological analysis of the vaginal smear for rats in all groups was performed to evaluate the state of the estrous cycle and then all animals were sacrificed and their ovaries were excised and handled for histological and immunohistochemical studies. Results: Estradiol valerate treated group showed irregular cycles or constant cycles in estrous phase (Persistent Vaginal Cornification, PVC) which were considered as signs of PCO. Histologically, there was a significant decline in the number of the different healthy follicles in the cortices with the presence of multiple cystic and atretic follicles and also large congested blood vessels with hemorrhage. Immunohistochemically, the number of i-NOS positive granulosa, theca, and interstitial cells increased significantly in this group with increase of image optical density (IOD) for all these positive cells. Pomegranate molesses supplementation with estradiol valerate in group IV has ameliorating effect on the vaginal smear, histological and immunohistochemical abnormalities of the ovaries. Conclusion: There is a potential benefit in using pomegranate molesses with EV induced PCOS. [ABSTRACT FROM AUTHOR]

To investigate the improvement and mechanism of Compound gossyl acetate tablets combined with Duyiwei capsules on anovulatory dysfunctional uterine bleeding induced by estradiol valerate in rats. A total of 40 female SD rats were randomly divided into two groups (blank group and model group). The anovulatory dysfunctional uterine model was prepared by giving rats estradiol valerate by gavage for 21 consecutive days. After the model rats were successfully prepared, they were divided into model group, positive group and treatment group according to the random method, in which the positive group and treatment group were given corresponding drugs by gavage respectively, and the blank group and model group were given the same volume of normal saline by gavage, and each group was given continuous gavage for 7 days. The uterine coefficients of each group were calculated. The serum estradiol (E2 ) and progesterone (P) levels were measured by enzyme-linked immunosorbent assay (ELISA), and the expression levels of matrix Metalloproteinases-9 (MMP-9) and vascular growth factor (VEGF) in the endometrial tissues were measured by immunohistochemistry. The serum Level of P in the model group was significantly lower than that in the blank group (P<0.05), and the expression levels of MMP-9 and VEGF in the endometrial tissues were significantly higher than that in the blank group (P<0.05). After administration, the serum P level of rats in both the treatment group and the positive group was significantly higher than that in the model group (P<0.05), and the expression levels of MMP-9 and VEGF in the endometrial tissues of rats were significantly lower than that in the model group (P<0.05). There was no significant difference between the treatment group and the positive group (P>0.05). Compound gossyphenol acetate tablet combined with Duyiwei capsule can significantly improve anovulatory dysfunction uterine bleeding, and the mechanism may be related to the regulation of the expression levels of MMP-9 and VEGF in endometrium. [ABSTRACT FROM AUTHOR]

Background: Compared with a natural process, surgically induced menopausal women have a higher bone loss rate. This study aims to evaluate early treatment with estradiol valerate on bone turnover markers after surgically induced menopause.Methods: This prospective study included 41 pre and perimenopausal women who underwent hysterectomy with oophorectomy for benign gynecologic conditions. Two weeks after the operation, all participants were assessed for menopausal hormone therapy (MHT) indications. Estrogen therapy was prescribed for those who had indications and accepted treatment (hormone treatment group). The others who had no MHT indication were allocated to the no-treatment group. Serum CTX and P1NP levels at preoperative and 12 weeks postoperative were measured and set as the primary outcome. Within the same group, serum CTX and P1NP before and after surgical menopause were analyzed using Wilcoxon signed-rank test. ANCOVA was used to compare serum CTX and P1NP at 12 weeks after surgical menopause between the two groups. Spearman's rank correlation coefficient analysis analyzed the correlation between age and baseline bone turnover markers. A p-value of < 0.05 was considered statistically significant.Results: At 12 weeks after surgery, there were no significant differences in serum CTX and P1NP levels in the hormone treatment group compared to baseline. In contrast, serum CTX and P1NP levels were significantly elevated among women who did not receive hormone treatment (p-value < 0.001 and 0.002, respectively). Serum CTX and P1NP at 12 weeks were significantly different between the two groups (p-value < 0.001 and 0.004, respectively).Conclusion: Early estrogen administration with oral estradiol valerate could significantly suppress the high bone remodeling in surgically induced menopausal women. Trial registration Thai Clinical Trial Registry identification number TCTR20190808004, retrospective registered since 2019-08-08. http://www.thaiclinicaltrials.org/show/TCTR20190808004 . [ABSTRACT FROM AUTHOR]

Attempts have been made over the years to replace ethinyl estradiol (EE) in combined oral contraceptives (COCs) with the less potent natural estrogen estradiol (E 2), or its prodrug, E 2 valerate (E 2 V), to improve their safety and tolerability. Recently, a COC incorporating a novel weak natural estrogen, estetrol (E 4), combined with drospirenone, has become available. We present a comparative analysis of the three prevailing estrogens used in COCs, focusing on their structure-function relationships, receptor-binding affinity, potency, metabolism, pharmacokinetic parameters, and pharmacodynamics. The binding affinity of EE to estrogen receptor (ER)α is twice that of E 2 , whereas its affinity for ERβ is about one-half that of E 2. E 4 has a lower binding affinity for the ERs than E 2. The high potency of EE is notable in its dramatic increase in estrogen-sensitive hepatic globulins and coagulation factors. EE and E 2 undergo extensive and comparable metabolism, while E 4 produces only a very limited number of metabolites. E 4 has the highest bioavailability among the three estrogens, with E 2 having <5%. Studies demonstrate consistent ovulation inhibition, although a higher dose of E 4 (15 mg) in COCs is required to achieve follicular suppression compared to E 2 (1–3 mg) and EE (0.01–0.035 mg). E 2 and E 4 in COCs may be less stimulatory of coagulant proteins than EE. Studies with E 2 /dienogest suggest a comparable risk of venous thromboembolism to EE/levonorgestrel, while data assessing risk with an E 4 -based COC are insufficient. Nevertheless, the E 4 -based formulation shows promise as a potential alternative to EE and E 2 due to its lower potency and possibly fewer side effects. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is the most common complex endocrine disorder affecting approximately 2–20% of reproductive aged females. Tumour Treating Fields (100–300 kHz) is a recent innovative, non-invasive therapeutic approach to cancer therapy. This frequency as an alternative therapy for the management of polycystic ovaries has not yet been explored. Objectives: To explore the effect of full-body exposure of 150 kHz Electromagnetic Radiation (EMR), on the development of polycystic ovaries in an estradiol valerate-induced PCO rat model. Method: Twenty-one female adult rats were divided into three groups (n = 7 each): control, Estradiol Valerate (EV) and EV + EMR groups. The EV + EMR group was subjected to full body exposure at 150 kHz EMR continuously for eight consecutive weeks. Estradiol valerate was administered orally to induce polycystic ovaries in EV and EV + EMR groups. Body and ovarian weights were recorded and analysed. The regularity of the estrous cycle was assessed in all three groups. The histological study of ovarian tissue was carried out by haematoxylin and eosin staining. The serum concentration levels of Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH) and testosterone were measured using the ELISA method. Results: The body and ovary weights did not differ significantly between the EV and EV + EMR groups. The estrous cycle was found to be irregular in both the EV and EV + EMR groups. Ovarian histology revealed near normal morphology with little or no degenerative and morphological changes in developing follicles in the exposed group. Histometrical analysis showed an increased number of developing follicles and a significant reduction in the number and size of follicular cysts (p < 0.05) in the EV + EMR group. Hormonal analysis revealed no significant difference in the testosterone and FSH levels between the EV + EMR and EV groups. However, the LH, LH/FSH ratio decreased significantly in the EV + EMR group compares to the EV group. Conclusion: The 150 kHz EMR appear to have little or no degenerative and morphological changes in the developing follicles, an increased number of typical developing follicles and a significant reduction in the number and size of the follicular cysts (p < 0.05). [ABSTRACT FROM AUTHOR]

Background: Endometrial thickness is regarded as an indicator of the receptivity of the endometrium. Patients preparing for frozen embryo transfer need some interventions in case their endometrium is thin. Objective: This study aimed to compare the clinical outcomes of oral administration of estradiol valerate with its vaginal type in women with inappropriate endometrial thickness. Materials and Methods: This cross sectional study comprised of 79 women (cycles) who had undergone frozen-thawed embryo transfer. On the 13th day of the cycle, vaginal sonography was performed in case the thickness of the endometrium was < 7 mm; in the oral group, the patients continued using oral estradiol valerate tablet. However, in the vaginal group, the participants applied estradiol valerate tablet vaginally. Finally, the chemical and clinical pregnancy rate, also, early miscarriage rate were compared between the two groups. Results: The early miscarriage rate was lower in the vaginal group in comparison with the oral group (p = 0.040). Women in the vaginal group showed a lower rate of chemical pregnancy compared to the oral group, but this difference was not statistically significant (25.0 vs. 34.4%, p = 0.440). The rate of clinical pregnancy in the two groups was not statistically significant, although the vaginal group had a higher pregnancy rate (22.5% vs. 15.6%, p = 0.464), especially in women older than 34 years (37.5% vs. 11.1%, p = 0.355). Conclusion: Vaginal administration of estradiol tablet in women with thin endometrium leads to a lower rate of early miscarriage. [ABSTRACT FROM AUTHOR]

Female causes account for 30 percent of the overall infertility cases, five percent were attributed to uterine factors. Endometrial thickness (ET) is one of the best predictors of implantation rate and continued success rate for pregnancy. There were possible beneficial effects of sildenafil citrate or estradiol on endometrial receptivity so some reports discussed these potential effects The aim: of this study is to compare the effect of estradiol valerate and vaginal sildenafil citrate on endometrial receptivity (endometrial thickness, serum Vascular Endothelial Growth Factor) and pregnancy rate in infertile Iraqi women Subjects and Methods: Sixty infertile women were included in this comparative prospective study undergoing stimulated cycles and timed intercourse. Patients diagnosed previously to have thin endometrium were divided randomly into two groups. In group A, thirty patients were given estradiol valerate 2 mg tablet 12 hourly. In group B, 30 patients were given sildenafil citrate 25 mg vaginally every 6 hours. Patients were evaluated by using trans-vaginal sonography (TVS) to determine and compare the effects of estradiol valerate and vaginal sildenafil citrate on endometrial thickness, pattern, and serum assessment of Vascular Endothelial Growth Factor VEGF levels and pregnancy outcome in both groups. Results: Mean endometrial thickness at HCG day was 9.19 mm in estradiol treated group and 8.86 mm in sildenafil treated group which was more in estradiol group but statistically insignificant (p>0.05). And endometrial triple line pattern in the Estradiol and sildenafil citrate groups was 96.6%, and 90% respectively. VEGF level in estradiol treated group was (220.5 ng/l) compared to sildenafil treated group (232.2), which is statistically significant difference (p <0.05). The pregnancy rates were 4 (16.7%) in group A and 11(73.3%) in group B which was statistically significant difference between the two groups (p<0.05) Conclusions: Both Sildenafil citrate and estradiol valerate may be used to improve endometrial receptivity, but this study showed that the pregnancy rate with Sildenafil was significantly higher than with estradiol. [ABSTRACT FROM AUTHOR]

Objective: To investigate the curative effect of estradiol valerate combined with medroxyprogesterone in the treatment of endometriosis and its impact on serum levels of carbohydrate antigen 125(CA125), carbohydrate antigen 199(CA199) and vascular endothelial growth factor(VEGF). Methods: 134 cases of endometriosis who treated from June 2016 to January 2018 in our hospital, according to random number table method these patients were divided into the control group(n=76) and observation group(n=58), the control group was treated with medroxyprogesterone and the observation group was treated with estradiol valerate on the basis of the control group, then clinical curative effect, serum levels of CA125, CA199 and VEGF cyst diameter, menstruation to be not moved a grade, dysmenorrhea before and after treatment, and adverse reactions occur in both group were compared. Results: the total effective rate in the observation group was higher than that in the control group, and the difference was statistically significant(P<0.05). Before treatment,serum levels of CA125, CA199 and VEGF, cyst diameter, menstrual irregularness score and dysmenorrhea score of the two groups were no significant difference(P>0.05). After treatment, serum levels of CA125, CA199 and VEGF, cyst diameter, dysmenorrhea score and dysmenorrhea score of the two groups were all decreased, and the difference between the observation group and the control group was statistically significant(P<0.05). Fatigue, insomnia and hot flashes occurred in both groups, and there was no statistically significant difference in the incidence of total adverse reactions between the two groups(P>0.05). Conclusion: Estradiol valerate combined with medroxyprogesterone can improve the efficacy of endometriosis, effectively reduce the level of serum CA125, CA199 and VEGF, and has a high safety. [ABSTRACT FROM AUTHOR]

Cyclophosphamide (CTX) as an alkylating agent is used for treating a range of tumor types and allergic diseases. However, high-dose application may induce rapid bone loss and increase the risk of osteoporotic fractures. Eldecalcitol (ED-71), a clinically approved active vitamin D analog, has been approved for osteoporosis treatment. It potently inhibited bone resorption while maintaining osteoblastic function in estrogen-deficient and high-turnover osteoporosis in model rats. The aim of the present study was to clarify the treatment effect of ED-71 on bone loss in a well-established rat model of osteoporosis with CTX administration. After 15 days of CTX treatment, ED-71 was administered, while estradiol valerate (E2V) was used as a positive control. At 2 and 4 weeks after ED-71 or E2V administration, rats were sacrificed and fixed. The tibiae were extracted for histochemical analysis using hematoxylin and eosin staining and immunohistochemistry. When compared with the untreated control group, the CTX group displayed clear osteoporotic features, including a decreased number of bone trabeculae and increased trabecular separation. ED-71 and E2V successfully rescued CTX-induced bone loss. The ED-71 group displayed denser and increasingly mature trabecular bone than the E2V group. Furthermore, ED-71 administration led to significant suppression of tartrate-resistant acid phosphatase (TRAP), cathepsin K (CK), matrix metalloproteinase 9 (MMP9), alkaline phosphatase (ALP) and Osteopontin (OPN), which was less pronounced than in E2V administration but was similar to the values exhibited in the normal control group. These results indicated that ED-71 had a moderate and increased effect on bone turnover compared with E2V. Therefore, the present study suggests that ED-71 is a potential inhibitor of CTX-induced osteoporosis, successfully rescuing bone loss without excessively suppressing bone turnover, and may be a suitable treatment for preventing bone loss in patients receiving CTX. [ABSTRACT FROM AUTHOR]

Follicular cystic ovary disease is a common reproductive disorder in women and females of domestic animals, characterized by anovulation and the persistence of follicle is a common cause of reproductive failure in mammalian. Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism (HA), chronic anovulation and polycystic ovaries, and it is a common reproductive endocrine disease with clinical manifestations including hirsutism, acne, infertility and obesity that can affect 5–20% of women in their reproductive age. Photobiomodulation (PBM) has been investigated and used in clinical practice, related to biomodulatory influences on cellular functions in animals and humans, both in vivo and in vitro. In this study, we include endocrine and reproductive features in a rat model for PCOS and the effects of PBM on ovarian activities. Forty-five adult female Wistar rats PCOS-induced by a single dose of the estradiol valerate (EV) were used in the study. After the EV injection for PCO induction, rats were divided into 9 groups (n = 5/group) named C30, C45 and C60 (Control group), S30, S45 and S60 (PCO group) and L30, L45 and L60 (PCO/Laser group). The rats were irradiated with laser 3 times/week. The results shown that EV PCO-induced rats had increased body mass, reduced ovary mass, and reduced GSI. The plasma levels of P4 and T were increased, and the LH plasma level was decreased by PBM stimulation. The number of ovarian follicles and corpus luteum were increased, and the number of ovarian cysts was decreased by PBM stimulation. Thus, reproductive and endocrine characteristics were modulated by PBM. • There are reductions in the numbers of follicles and CL, in addition to the appearance of follicle cysts in the PCO group. • The highest number of follicular cysts occurred in the PCO group 60 days after EV injection. • The PCO animals submitted to PBM for 60 days presented fewer follicular cysts than the PCO animals. • The number of follicles found for the 60-day PCO/laser group was higher than for the PCO group. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Hyperoside, an active flavonoid glycoside isolated from many traditional Chinese medicines, has received much attention because of its potential role in osteoporosis treatment. In the present study, we investigated the antiosteoporotic role and mechanism of hyperoside on ovariectomized (OVX) mice. Sixty female Kunming mice received one of three treatments orally for 12 weeks: estradiol valerate (0.3 mg/kg body weight/day), hyperoside (20, 40, or 80 mg/kg body weight/day), or vehicle. We found that hyperoside was effective in preventing osteoporosis by increasing bone mineral density, restoring trabecular bone micro-architecture, and enhancing bone strength. Meanwhile, the activities of bone resorption markers, including tartrate-resistant acid phosphatase 5b (TRAP-5b) and C-terminal telopeptide of type I collagen (CTX), were significantly decreased, while the bioactivity of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BALP), were significantly increased. Mechanistically, hyperoside reduced the expression of receptor activator of nuclear factor-κB ligand (RANKL), TNF-receptor-associated factor 6 (TRAF6), phosphorylated inhibitor of nuclear factor-κB α (IκBα), NF-kB p65, and nuclear factor of activated T cell cytoplasmic 1 (NFATc1) and promoted the expression of osteoprotegerin (OPG). Therefore, the function of hyperoside might be related to the inhibition of the TRAF-6 mediated RANKL/RANK/NF-κB signaling pathway and the elevation of the OPG/RANKL ratio. These data demonstrated that hyperoside has potential applications as a drug for osteoporosis treatment. [ABSTRACT FROM AUTHOR]

Background: To investigate the efficacy and safety of estradiol valerate (EV)/dienogest (DNG) for the management of heavy menstrual bleeding (HMB) in Asian and non-Asian women desiring contraception. Materials and Methods: In this multicenter, double-blind, phase III study, women were randomized 2:1 to receive EV/DNG or placebo tablets daily for seven 28-day cycles. The primary endpoint was the absolute change in menstrual blood loss (MBL) volume between the run-in and efficacy phases (90 days each). Secondary endpoints included the proportion of women with successful treatment (i.e., no episodes of MBL ≥80 mL and a decrease of <50% in MBL), percent change in MBL from the run-in phase, and change in hemoglobin and serum ferritin levels. Adverse events (AEs) were monitored throughout the study. Results: Of the 341 women (mean age 34.7 ± 7.7 years; 309 Asians, 32 non-Asians) randomized, 270 completed the study. Mean reduction in MBL volume from run-in phase was significantly greater with EV/DNG than placebo (366.75 mL vs. 149.14 mL; p < 0.0001), with ∼52% and 12% of women, respectively, experiencing successful treatment. Percent decrease in MBL volume from the run-in phase was significantly greater with EV/DNG than placebo (63.5% vs. 24.8%; p < 0.0001). Hemoglobin and serum ferritin levels were increased with EV/DNG compared with placebo. Study drug-related AEs were reported in 16.3% and 8.2% of women with EV/DNG and placebo, respectively, none of which were of severe intensity. Conclusions: EV/DNG may be a safe and effective option in the treatment of HMB in Asian and non-Asian women who desire contraception. [ABSTRACT FROM AUTHOR]

Abstract Aim Cynomorium songaricum Rupr., an edible and important Traditional Chinese medicine has long been used in folk for treatment of kidney deficiency, was chosen to estimate the antiosteoporotic activity and underlying molecular mechanism on rats induced by ovariectomy (OVX). Main methods 9 of 45 rats were underwent bilateral laparotomy without removing the ovaries as sham group, remains were underwent bilateral ovariectomy and equally randomized into four groups: with vehicle (0.5% CMC-Na) as model group, estradiol valerate (1 mg/kg body weight/day) as positive control, with 100 and 300 mg/kg body weight/day of ethanol extracts of C. songaricum extract (CSE) as low and high dosage groups, respectively. Key findings After 12 weeks of continues orally intervention, the decreases of bone mineral density, bone mineral content, tissue mineral content, as well as the increases of bone trabecular separation and bone resorption markers were significantly reversed by CSE in the OVX rats, and in particular, a contradictory phenomenon on calcium and phosphorus contents was observed and elucidated. Mechanistically, the expressions of tumor-necrosis factor receptor-associated factor 6 (TRAF 6), nuclear factor kappa B (RANK) and its ligand (RANKL), as well as the nuclear factor kappa B (NF-κB), phosphoinositide 3‑kinase (PI3K) and protein kinase B (AKT) levels were significantly down-regulated by CSE intervention, whereas the osteoprotegerin (OPG) was significantly up-regulated by CSE as compared to the control. Significance Concisely, C. songaricum exhibited potential therapeutic effect on bone metabolism of ovariectomized rats, and this effect was possibly exerted by RANKL/RANK/TRAF6 mediated down-regulation of NF-κB and PI3K/AKT pathways. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Objective To study the possible protective role of montelukast in endometrial hyperplesia (EH) rat model, induced by estradiol valerate (EV). Methods/materials Thirty six female albino Wistar rats were classified into 7 groups: normal control, EV (2 mg/kg/day, p.o.), montelukast (10 mg/kg/day, p.o.), montelukast (1 mg/kg/day, p.o.) + EV (2 mg/kg/day, p.o.), montelukast (10 mg/kg/day, p.o.) + EV (2 mg/kg/day, p.o.), montelukast (20 mg/kg/day, p.o.) + EV (2 mg/kg/day, p.o.) groups. Uterine malondialdehyde (MDA), superoxide dismutase (SOD), total nitrites (NO) and serum total antioxidant capacity (TAC) were determined. Uterine, serum total cholesterol, high density lipoprotein (HDL) and tumor necrosis factor (TNF)-α were measured. Histopathological examination of the uterine tissue was also done. In addition, immunohistochemistry was done using Phosphatase and tensin homolog (PTEN) and inducible nitric oxide synthase (iNOS) antibodies. Results Our results showed that montelukast in dose dependant manner improves oxidative stress, lipids profile and TNF α which were affected by EV. Moreover, immunohistochemical examination revealed that montelukast markedly reduced iNOS expression, while expression of PTEN was markedly enhanced, as compared to EV group. The protective effects of montelukast were also verified histopathologically. Conclusions Montelukast in dose dependant manner provided biochemical and histo-pathological improvement in EV induced EH, through its anti-inflammatory, antioxidant activity and inhibition of iNOS expression with induction of PTEN expression. [ABSTRACT FROM AUTHOR]

Background: Both oral contraceptive pills (OCPs) and estradiol valerate (E2) have been used to schedule a gonadotropin-releasing hormone antagonist in vitro fertilization (IVF) cycles. Since the suppression of follicle-stimulating hormone by OCPs can stay 5-7 days after stopping the pills, it seems that starting the gonadotropin-releasing hormone (GnRH) after 6 days of pre-treatment discontinuation may be important in IVF outcomes. Objective: The aim of the present study was to determine the number of mature oocyte and pregnancy rate of three pretreatment methods for fresh embryo transfer cycles. Materials and Methods: In this randomized controlled trial, two-hundred ten women (18-35 yr and less than 2 previous IVF attempts) undergoing IVF with the GnRH antagonist protocol were randomized to the OCP, E2, and no pretreatment arms. OCP group (n=53) received OCP (ethinyl estradiol30 µg and levonorgestrel150 µg), E2 group (n=63) received 4 mg/day oral E2 (17ß-E2) for 10 days from day 20 of the previous cycle and GnRH antagonist stimulation was started 6 days after the interruption of OCP and E2. The control group (n =70) did not receive any pretreatment. Results: No significant difference was observed in the mean number of the mature oocyte, endometrial thickness, and embryo quality. The pregnancy rate in E2 group was higher than the two other groups (42.9% vs 39.6% and 34.3% in OCP and control group, respectively), but the difference was not statistically significant (p=0.59). Conclusion: It seems OCP or E2 pretreatment could not improve the fresh IVFembryo transfer outcomes. [ABSTRACT FROM AUTHOR]

Background: Letrozole is as effective as clomiphene citrate for induction of ovulation in patients with PCOS. Adequate endometrial development is required for pregnancy to occur, and pregnancy rates were found to be higher when the endometrium reached at least 10 mm thickness. Objective: To study the effect of estradiol valerate on the endometrial thickness and subsequently the pregnancy rate in PCOS cases receiving letrozole for induction of ovulation as compared to letrozole alone. Study design: A randomized controlled study. Setting was at the infertility clinic of the Cytogenetic and Endoscopy Unit, Zagazig University Hospital. Material and methods: The study included 273 patients who underwent ovulation induction and timed intercourse. Patients were divided into 2 groups: controlled ovarian stimulation was done in group 1 by letrozole with addition of estradiol valerate and in group 2 by letrozole alone. Results: As regard the clinical pregnancy rate, we found a statistically significant difference between the 2 studied groups, with documented clinical pregnancy in 34 patients in group 1 compared to only 16 patients in group 2. Conclusion: This study showed that the pregnancy rate achieved with letrozole/estradiol valerate combination was significantly higher than with letrozole alone. This was attributed to the improvement of endometrial thickness by estradiol valerate. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prevalence of breast tenderness in a population treated with menopausal hormone therapy (MHT) or Cimicifuga foetida extract.Methods: A prospective, randomized, controlled trial was conducted. Ninety-six postmenopausal women were randomly assigned to three groups: group A, 1 mg estradiol valerate daily plus 4 mg medroxyprogesterone acetate (MPA), days 19-30; group B, 1 mg estradiol valerate daily plus 100 mg micronized progesterone (MP), days 19-30; group C, 100 mg C. foetida extract daily. Breast tenderness was evaluated daily for 12 months.Results: Seventy-three patients completed the study. Group A had the highest prevalence of breast tenderness, while group C had the lowest. More than 50% of all participants reported no symptoms throughout the period. The participants in group A experienced a sharp increase in breast tenderness after treatment, but decreased after 1 month. No significant decline was found in the duration of pain in group B. The patients in group C reported no remarkable changes after 1 month. Compared to estrogen only, estrogen plus MPA/MP led to a higher incidence of prolonged breast symptoms.Conclusions: Compared to MHT groups, C. foetida extract had the lowest prevalence of breast tenderness. Most participants experienced mild or no symptoms. [ABSTRACT FROM AUTHOR]

Background: To investigate the efficacy and safety of a combined oral contraceptive containing estradiol valerate and dienogest (EV/DNG) in healthy Asian women.Methods: In this multicenter Phase III study, women received oral EV/DNG in a 28-day regimen for 13 cycles. The primary efficacy endpoint was the number of unintended pregnancies, measured by the Pearl Index (PI); secondary efficacy endpoints included bleeding pattern and cycle control parameters. Adverse events were monitored during the study and overall satisfaction with treatment was determined on completion of the study.Results: A total of 954 Asian women (97.7% of subjects assigned to study medication; mean age 33.4 years) were treated. Five pregnancies were reported during EV/DNG treatment over 796.34 relevant woman-years of exposure, giving an unadjusted PI of 0.63 and a cumulative failure rate of 0.0049; 3 pregnancies during EV/DNG treatment over 760.35 relevant woman-years of exposure gave an adjusted PI of 0.39. The bleeding pattern improved during the reporting periods within the study. The proportion of women who experienced withdrawal bleeding decreased with treatment (84.9% of women during Cycle 1 vs 79.3% in Cycle 13), and the mean length of withdrawal bleeding decreased with treatment (4.2 vs 3.4 days). The number and maximum length of intracyclic bleeding/spotting episodes also decreased with EV/DNG. EV/DNG was well tolerated, and 92% of women included in the study were very satisfied or somewhat satisfied with EV/DNG.Conclusion: EV/DNG showed high contraceptive efficacy, was well tolerated in Asian women, and may be effectively used in this population.Clinical trials registry: ClinicalTrial.gov identifier: NCT01638910. [ABSTRACT FROM AUTHOR]

The biologically transformed product of estradiol valerate, namely 3,7α‐dihydroxyestra‐1,3,5(10)‐trien‐17‐one monohydrate, C18H22O3·H2O, has been investigated using UV–Vis, IR, 1H and 13C NMR spectroscopic techniques, as well as by mass spectrometric analysis. Its crystal structure was determined using single‐crystal X‐ray diffraction based on data collected at 100 K. The structure was refined using the independent atom model (IAM) and the transferred electron‐density parameters from the ELMAM2 database. The structure is stabilized by a network of hydrogen bonds and van der Waals interactions. The topology of the hydrogen bonds has been analyzed by the Bader theory of `Atoms in Molecules' framework. The molecular electrostatic potential for the transferred multipolar atom model reveals an asymmetric character of the charge distribution across the molecule due to a substantial charge delocalization within the molecule. The molecular dipole moment was also calculated, which shows that the molecule has a strongly polar character. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a common form of the endocrine disease which is associated with metabolic dysfunction. PCOS and type 2 diabetes mellitus are related in multiple aspects and are similar in many pathological features. Anti-diabetic effects of Nigella sativa and protective effects of it on reproductive system have been suggested in some reports. Objective: The aim of current study was to evaluate the effects of thymoquinone, the main components of Nigella sativa, on PCOS model of rats. Materials and Methods: Intraperitoneal injection of estradiol valerate for 25 days was used to induce PCOS in Wistar rats, followed by intraperitoneal administration of 8 and 16 mg/kg thymoquinone for 30 days. Rats were divided into 5 groups; control, sham or PCOS, experiment-1 (PCOS and 8 mg/kg thymoquinone), experiment-2 (PCOS and 16 mg/kg thymoquinone), and metformin (PCOS and metformin administration, 100 mg/kg) groups. All of the animals were subjected to serum biochemical analysis of blood and histopathological study of ovaries. Results: Estradiol valerate induced PCOS while administration of thymoquinone recovered it. The body weight, ovarian morphology, and ovulation had been improved and the serum biochemical parameters including glucose, triglyceride, total cholesterol, low-density lipoprotein, high-density lipoprotein, luteinizing hormone, and follicle stimulating hormone were reversed after thymoquinone intervention. Conclusion: Our data suggest that thymoquinone has improvement effects on an ovarian function and ovulation in the PCOS rat model. Therefore, thymoquinone and Nagilla sativa could be used as a protective agent and as an adjunct treatment in PCOS patients. [ABSTRACT FROM AUTHOR]

The menopausal period, an inevitable physiological process for women, is frequently associated with physiological and psychological dysfunction attributable to substantial fluctuation and gradual decrease in female hormones induced by ovarian failure, leading to corresponding symptoms and diseases that impact multiple systems in the body to varying degrees. As prior studies have focused primarily on menopausal syndrome-related pathophysiological changes and hormone replacement therapy effects, here we approached menopausal disease incidence risk and pathogenesis through systemic plasma proteomics analysis. Female Sprague-Dawley rats were randomly divided into sham, ovariectomized, and estrogen treatment after ovariectomy groups (n = 9 per group). Tandem Mass Tag quantitative proteomics analysis of their plasma identified over 900 proteins by MS. Between group fold change of >1.2 and p < 0.05 (Student’s t -test) identified 121 (including 36 up-regulated and 85 down-regulated), 117 (69 up-regulated and 48 down-regulated), and 109 (41 up-regulated and 68 down-regulated) differentially expressed proteins between groups, respectively. Of these, 5 (GHR, LIFR, apoA IV, RTN, and Lin28b) were verified by parallel reaction monitoring to be reliable. Further application of optimized screening criteria and performance of a series of bioinformatics analyses allowed the selection of 35 optimal differentially expressed proteins. Gene ontology annotation results suggested that the differentially expressed proteins are mainly annotated as protein binding, cell, and single organism process in terms of molecular function, cell composition, and biological process, respectively. KEGG pathway analysis indicated that the PI3-Akt pathway has the highest aggregation degree of differentially expressed proteins. Protein-protein interaction analysis noted GLUT4 as an important node protein. This research is the first to comprehensively analyze plasma protein changes, together with estrogen efficacy, in ovariectomized rats. The findings facilitate our understanding of the molecular mechanism of systemic menopausal changes and provide valuable clues for developing diagnostic biomarkers for menopausal dysfunctions and selecting clinical therapeutic strategies. [ABSTRACT FROM AUTHOR]

Ultra-trace detection of estradiol valerate (EV) in whole blood samples was done by coupling Fast Fourier transform square wave voltammetry (FFTSWV) and electromembrane extraction (EME). For the first time, a novel carbon paste electrode (CPE) modified with Terbium carbonate (Tb 2 (CO3) 3 ) nanoparticles was used for FFTSWV determination of EV. The important parameters in electro membrane extraction recovery of EV, containing extraction time, electrical potential and pH of donor phases, were optimized by Central composite design and response surface methodology. By applying a low voltage of 7 V during 20 min of extraction, EV was migrated from the sample solution (pH 4), into a thin layer of 1-octanol in the pores of a porous flat sheet membrane and then into the acceptor solution (pH 5). Under the optimal conditions, EV was effectively extracted from the whole blood sample with recovery percentage of 67%.The method showed two wide linear ranges 0.1–1300 and 1300–10,000 ng/mL with determination coefficients of 0.995 and 0.991, respectively. Limits of detection and quantification of 0.01 ng/mL and 0.1 ng/mL were acquired, respectively. The intra- and inter-day precisions (RSD%, n = 3) were <4.2% and 6.3%, respectively. [ABSTRACT FROM AUTHOR]

Objective:The study was to evaluate whether fibrotic markers, endometrial receptivity markers and SDF-1/CXCR4 had been changed in the treatment of intrauterine adhesions (IUAs) by different dosages of estrogen. Study design:A total of 39 patients with IUAs were treated with EV 4 mg or 9 mg randomly post-surgery. TGF-β1/MMP-9, VEGF/αvβ3 and SDF-1/CXCR4 were detected in endometrial tissue before and after treatment by real-time PCR and Western blot. Results:TGF-β1 and MMP-9 expression significantly decreased after treatment for 3 months than before (p < .05), the falling range was larger with EV 4 mg than 9 mg in the mild-moderate degree IUAs (p < .05); Integrin avβ3 expression significantly increased after treatment for 3 months than before (p < .05), the variation range was larger with EV 4 mg than 9 mg (p < .05); CXCR4 expression had no significant change after treatment 3 months compared to that before treatment (p > .05). SDF-1 presented an upward tendency at early phase, and it came back to the level of pre-surgery. But there were no significant difference between treatment with 4 mg and 9 mg in the rate of menstrual restoration and pregnancy follow-up 3 months after the treatment. Conclusions:Endometrium fibrosis may be inhibited and endometrium receptivity may be improved by estrogen with moderate dosage therapy. Compared to the large one, it seems to be advantageous. [ABSTRACT FROM AUTHOR]

To understand the impact of exposure to steroids in the early step of ovary development (a stage occurring in uterus in humans), we studied neonatal exposure to estradiol valerate (EV) in rats regarding polycystic ovary (PCO) development as well as expression of androgen receptor (Ar) and anti-Müllerian hormone (AMH), a marker of ovarian follicular development. Rats exposed to one dose of EV (10 mg/kg, sc) during their first 12 h of life were euthanized at 2, 30 and 60 days of age. Gene array and real-time PCR studies showed Ar and AMH up regulation in the ovary at 2 days of age and persisted at 60 days of age, when a PCO phenotype was evident with increased levels of Ar and AMH proteins. The single neonatal exposure in rats suggests participation of EV in developing PCO syndrome. Its persistence also suggests that estradiol reprograms ovarian function and disease during adulthood. [ABSTRACT FROM AUTHOR]

Background:While progesterone affects sleep, different types of it might affect sleep differently. Methods:One hundred Thai women, who complained of insomnia, visited the Menopause Clinic at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand from February 2014 to March 2015, and were divided randomly into two groups. Both groups received daily hormonal treatment that included estradiol valerate (progynova) at 1 mg. The first group also received dydrogesterone (duphaston®) at 10 mg and the second group micronized progesterone (utrogestran®) at 100 mg. The clinical symptoms and Pittsburgh Sleep Quality Index (PSQI) were recorded for three consecutive months after treatment. This study was registered with clinicaltrial.gov (code number NCT02086032). Results:Sleep quality improved in both groups (10.52 ± 4.27 to 4.91 ± 3.15 in the dydrogesterone group and 10.16 ± 3.60 to 6.27 ± 3.04 in the micronized progesterone group,p value 0.08). Women in the micronized progesterone group had fewer overall side effects than those in the dydrogesterone group. Conclusion:Sleep quality of peri-postmenopausal women with insomnia improved dramatically after the first month of hormonal treatment. However, more participating patients are necessary to ascertain the differences in sleep quality from dydrogesterone and micronized progesterone treatment. [ABSTRACT FROM AUTHOR]

The success rates of in-vitro fertilization (IVF) have plateaued over the last few years. Various factors affect the outcomes, endometrial receptivity being one such. In IVF with own oocytes, endometrial growth is brought about by the estrogen secreted by the multiple follicles recruited as a result of controlled ovarian hyperstimulation. In donor egg IVF however, endometrium has to be prepared artificially with hormone replacement. Various regimens have been suggested for the same but a consensus regarding the optimal method is still lacking. This small observational study takes a look at the efficacy of oral micronized estradiol valerate in improving endometrial thickness in women undergoing donor-egg IVF both with fresh and frozen-thawed embryos. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated acceptability, user satisfaction, body weight control and general well-being of estetrol (E4) combined with either drospirenone (DRSP) or levonorgestrel (LNG).Methods: In this open-label, multi-centre, dose-finding, 6-cycle study, 396 healthy women of reproductive age were randomised into five treatment groups in a 24/4-day regimen: 15 mg or 20 mg E4 combined with either 3 mg DRSP or 150 μg LNG, and as reference estradiol valerate (E2V) combined with dienogest (DNG). Data on acceptability, user well-being, satisfaction and body weight were collected.Results: The number of completers was the highest in the 15 mg E4/DRSP group (91.1%), and the lowest for 20 mg E4/LNG (70.1%). The largest proportion of treatment satisfaction was reported for 15 mg E4/DRSP (73.1%), and the lowest for 15 mg E4/LNG (50.6%). The number of women willing to continue with the assigned study treatment was the highest in the 15 mg E4/DRSP group (82.1%) and the lowest for 20 mg E4/LNG (58.3%). Well-being with E4/DRSP combinations was statistically significantly better than with E4/LNG combinations: OR (95% CI) 2.00 (1.13; 3.53) and 1.93 (1.06; 3.56) for 15 and 20 mg E4, respectively, and comparable to E2V/DNG. Proportion of women with a 2 kg or more weight loss after 3 and 6 cycles was the highest in the 15 mg E4/DRSP group (30.7 and 36.7%, respectively).Conclusions: The present study shows that 15 mg estetrol combined with 3 mg DRSP is associated with a high-user acceptability and satisfaction, and with a favourable body weight control. [ABSTRACT FROM AUTHOR]

To investigate the lipid metabolism dysregulation in the liver of ovariectomized (OVX) rats and effects of estradiol valerate (E) and remifemin (ICR) thereon, forty female Sprague-Dawley rats were randomly divided into sham-operated (SHAM), OVX, OVX+E, and OVX+ICR group. After 4 weeks’ E or ICR treatment, serum estrogen, cholesterol, and triglyceride levels; lipid droplets in hepatocytes; hepatocyte morphology; and the expression of estrogen receptor α (ERα), liver X receptor (LXR), and sterol regulatory element binding proteins (SREBPs) in the liver of the rats were assessed. OVX rats had significantly decreased serum estrogen levels, which significantly increased after treatment with E but not with ICR. Serum triglyceride levels and the amount of lipid droplets in hepatocytes increased after ovariectomy, and significantly decreased after E treatment. In addition, ICR treatment markedly increased serum triglyceride levels and lipid droplet size. No significant differences in the serum cholesterol levels were observed among the four groups. After ovariectomy, hepatocyte mitochondria became hypertrophic and misformed, which were reversed with E or ICR treatment. ICR-treated rats also showed endoplasmic reticulum disorganization. After ovariectomy, ERα and LXR levels significantly decreased while SREBP expression increased. E treatment increased ERα and LXR levels while ICR treatment only increased LXR expression. E treatment decreased SREBP-1c levels, whereas SREBP-1c levels increased with ICR treatment. Treatment with E significantly reversed the ovariectomy-induced dysregulation of hepatocyte lipid metabolism, which was, however, exacerbated with ICR treatment. The effects of E and ICR on hepatocyte lipid metabolism may involve the regulation of LXR and SREBP-1c. [ABSTRACT FROM AUTHOR]

Hot flushes are common in menopause. Norepinephrine (NE), primarily synthesized in the locus coeruleus (LC), plays a major role in central thermoregulation. Furthermore, we previously observed decreased dopamine beta hydroxylase (DβH), a key enzyme in NE synthesis, in LC neurons following ovariectomy. In this study, we explore the mechanisms underlying decreased NE levels in the LC (LC-NE) in ovariectomized (OVX) rats, and the modulating effects of estradiol valerate (E2) and black cohosh (ICR). We used high-performance liquid chromatography to detect LC-NE in SHAM, OVX, OVX-E2, and OVX-ICR groups. Western blotting and immunohistochemistry were performed to investigate the expression of NE metabolic enzymes, the NE reuptake transporter (NET), and estrogen receptors (ERs) in the LC. We observed significant LC-NE decreases in the OVX group. E2 and ICR enhanced LC-NE but did not restore them to SHAM levels. Ovariectomy affected NE synthesis, degradation, and reuptake. Levels of NE catabolic enzymes monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) decreased, while NET expression increased. E2 restored MAOA and COMT to SHAM levels but had no effect on NET. ICR restored COMT and NET to SHAM levels but had no effect on MAOA. Moreover, the OVX group also exhibited decreased expression of ERα and ERβ. E2 enhanced the expression of ERα and ERβ, while ICR only enhanced ERβexpression. Taken together, reduced NE in OVX rats resulted from reduced synthesis and increased degradation and reuptake. E2 and ICR may regulate these processes in different ways through various ERs. [ABSTRACT FROM AUTHOR]

Menopause is a cardiovascular risk factor in women, and cardiovascular changes during perimenopause can increase the risk. We observed the influence of plasma adrenalin and norepinephrine and their metabolites on the cardiovascular system and the rectification effect of estrogen in ovariectomized rats. Fifty-four adult female Sprague-Dawley rats were randomly divided into sham (Sham), ovariectomized (OVX), or ovariectomized + estrogen treatment groups (OVX + E), with 18 rats in each. The Sham and OVX groups were given normal saline and the OVX + E group was given estradiol valerate beginning 2 weeks after ovariectomy and continuing for 4 weeks. Radioimmunoassay, high-performance liquid chromatography, high-performance liquid chromatography-tandem mass spectrometry, and chromatography-spectrophotometry were used to detect estradiol, adrenalin, norepinephrine, metanephrine, and normetanephrine in plasma and vanillylmandelic acid in urine. Echocardiography, Doppler blood flow detection technologyand hamnatodynamometer were applied to assess cardiovascular function. After ovariectomy, levels of estrogen reduced, adrenalin and metanephrine increased, and norepinephrine and normetanephrine in the plasma and vanillylmandelic acid in urine decreased. Symptoms indicative of cardiac diastolic dysfunction, including decreased diastolic left ventricular cavity capacity, increased wall thickness and decreased cardiac rate were observed. Different degrees of vasomotor dysfunction appeared in different peripheral positions, and the tail vessels were in relatively systolic conditions. However, the claw pad vessels were diastolic. Besides, blood pressure also increased. After ovariectomy, estrogen levels reduced and the metabolic processes of adrenalin and norepinephrine changed, which impacted cardiovascular functions. Changes of adrenalin and norepinephrine and its metabolites were correlated with the cardiovascular function. Cardiovascular disease occurred during the perimenopausal period. Estrogen replacement therapy can mitigate, rectify, and improve menopause-related conditions such as hot flash. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders that can lead to irregular menstrual cycles and hyperandrogenism. Reduced levels of progesterone and increased estrogen in these women can perpetually stimulate the endometrial tissue of the uterus. In this study, we assess the effect of PCOS induction by estradiol valerate (EV) in a rat model. Materials and Methods: In this experimental study, adult female Wistar rats that weighed approximately 200 g were divided into control, sham, and experimental groups (n=6 per group). The experimental group received subcutaneous injections of 2 mgEV for induction of PCOS. We confirmed the presence of PCOS in the experimental group rats. Rats from all groups were subsequently killed, after which their uteri were removed and fixed for histo-logical and cytological analyses. The uterine tissue sections were stained with hematoxylin and eosin (H&E) and iron hematoxylin (iron-H). We examined epithelium height, thickness of the uterus wall, and frequency of the mitotic cells. The data were assessed at α=0.05. Results: Uterine tissue findings from the experimental group showed significant increases in the height of the uterus luminal epithelium, the thickness of the uterus wall, and the frequency of eosinophils in the endometrial stroma. We observed an increased frequency of mitotic cells in the experimental group in both luminal and glandular epithelia of the uterus. An increased rate of the glandular epithelium region was noticeable and significant. Conclusion: Induction of PCOS by EV could change the proliferation rate in the endometrial tissue of the uterus. [ABSTRACT FROM AUTHOR]

6-Gingerol is the major pungent ingredient of ginger with anti-inflammatory and antioxidant properties. In this study, we evaluate the effects of 6-gingerol on the biochemical parameters and ovarian histological improvements in estradiol valerate (EV) induced PCOS rats. Thirty six female Wistar rats were divided into 4 groups: control, received normal diet, PCOS control, received 4 mg/kg EV injection for 28 days and two experimental groups, received an EV injection for 28 days and followed by 6-gingerol (200 μg/ kg and 400 μg/ kg ) for 14 days. The administration of EV led to increase body and ovarian weights, abnormality in serum sex steroid profile, decrease in antioxidant activity and increase in COX-2 gene expression. 6-gingerol treatments, particularly the 400 μg/ kg dose, markedly attenuated these alterations. 6-gingerol showed beneficial effects in the EV induced PCOS rats via decreased expression of COX-2, restored biochemical parameters to normal and decreased of cysts in the ovaries. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the real-use contraceptive effectiveness of the combined oral contraceptive containing dienogest and estradiol valerate (DNG/EV) and whether DNG/EV compared to other combined oral contraceptives (oCOC) has a negative effect on return to fertility.Methods: Transatlantic, prospective, non-interventional cohort study conducted in the USA and seven European countries with two main exposure groups and one exposure subgroup: new users of DNG/EV and other COC (oCOC), particularly levonorgestrel-containing COCs (LNG). In a planned secondary analysis, pregnancy outcomes were investigated including contraceptive effectiveness and pregnancy following contraceptive cessation. The influence of age, parity and OC-type were assessed.Results: 50,203 COC users were followed for 105,761 woman-years (WY). There were 677 unintended pregnancies reported: 451 in the USA and 226 in Europe. The contraceptive failure rate in Europe was 0.5 events/100 WY (95% CI: 0.4-0.5) and in the USA 1.9 events/100 WY (95% CI: 1.7-2.1). Differences in compliance (1.3 pregnancies/100 WY) accounted for 90% of the geographical difference seen between Europe and the USA. DNG/EV showed lower contraceptive failure rates compared to the comparators; 0.9% DNG/EV, 2.1% oCOC and 2.8% LNG after 4 years. Overall, 1167 (2.3%) of women stopped contraceptive use with the intention of becoming pregnant with 89% conceiving within 2 years. No significant differences were seen between groups after adjusting for age.Conclusion/discussion: DNG/EV is associated with similar contraceptive effectiveness in typical-use settings when compared to oCOC and LNG. There was no difference observed between cohorts in fertility following OC use. [ABSTRACT FROM AUTHOR]

Objective: To investigate the estradiol valerate combined Kunningan Pill on serum hormone level and immune functions in patients with climacteric syndrome. Methods: 120 cases of menopausal syndrome in our hospital were selected and randomly divided into the experiment group and the control group with 60 cases in each group. The control group were treated with estradiol valerate tablets 1 mg/time, 1 times/d; the patients in the experiment group were given Kunningan Pill based on the control group, 3 g/time, 3 times/d, oral. Treatment for 8 consecutive weeks. After the treatment,the serum follicle stimulating hormone (FSH), estradiol (E2), CD3+, CD4+, CD8+, Kupperman score and the clinical efficacy of patients were detected and compared. Results: Compared with before treatment, the FSH, CD8+,Ki score levels decreased (P＜0.05), E2, CD3+, CD4+ levels were significantly increased (P＜0.05) after treatment of two groups of patients; compared with the control group, FSH, CD8+, Ki score levels were lower (P＜0.05), E2, CD3+, CD4+ levels were higher, clinical treatment of total efficiency was higher (P＜0.05) Conclusion: Estradiol valerate combined Kunningan Pill can increased menopausal syndrome patients,the level of serum E2, reduce FSH levels, enhance the immune function and the clinical. [ABSTRACT FROM AUTHOR]

Objectives: The International Active Surveillance study "Safety of Contraceptives: Role of Estrogens" (INAS-SCORE) investigated the cardiovascular risks associated with the use of a combined oral contraceptive (COC) containing dienogest and estradiol valerate (DNG/EV) compared to established COCs in a routine clinical setting.Study Design: Transatlantic, prospective, noninterventional cohort study conducted in the United States and seven European countries with two main exposure groups and one exposure subgroup: new users of DNG/EV and other COC (oCOC), particularly levonorgestrel-containing COCs (LNG). All self-reported clinical outcomes of interest (OoI) were validated via attending physicians and relevant source documents. Main OoI were serious cardiovascular events (SCE), particularly venous thromboembolic (VTEs) events. Comprehensive follow-up procedures were implemented. Statistical analyses were based on Cox regression models.Results: A total of 50,203 new COC users were followed up for up to 5.5years (mean value, 2.1years). Overall 20.3% and 79.7% of these women used DNG/EV and oCOC (including 11.5% LNG users), respectively. A low loss to follow-up of 3.1% was achieved. Based on 47 (VTE) and 233 (SCE) events, the primary analysis (European data set) yielded adjusted hazard ratios for DNG/EV vs. oCOC of 0.4 and 0.5, respectively. The upper bounds of the 95% confidence intervals were 0.98 (VTE) and 0.96 (SCE). The corresponding hazard ratios for DNG/EV vs. LNG showed similar point estimates but the confidence intervals included unity.Conclusion: DNG/EV is associated with similar or even lower cardiovascular risk compared to oCOC and LNG.Implication Statement: A COC containing DNG and EV is associated with similar or even lower cardiovascular risk compared to COCs containing levonorgestrel or other progestogens. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to assess vaginal bleeding patterns and cycle control of oral contraceptives containing estetrol (E4) combined with either drospirenone (DRSP) or levonorgestrel (LNG).Study Design: An open-label, multicentre, randomised, dose-finding study lasting six cycles in healthy women aged 18-35 years was used. Four treatments (15 mg or 20 mg E4, combined with either 3 mg DRSP or 150 mcg LNG) were administered in a 24/4-day regimen. A marketed dosing regimen of estradiol valerate with dienogest (E2V/DNG) served as reference since it contains (like E4) a natural oestrogen.Results: A total of 396 women were randomised, of whom 389 received study medication, and 316 completed the study. By cycle 6, the frequencies of unscheduled bleeding and/or spotting and absence of withdrawal bleeding were the lowest in the 15 mg E4/DRSP group (33.8% and 3.5%, respectively). In the E2V/DNG reference group, these frequencies were 47.8% and 27.1%, respectively. By cycle 6, the frequency of women with absence of withdrawal bleeding was <20% for all E4 treatment groups: 3.5-3.8% combined with DRSP and 14.0-18.5% combined with LNG. By cycle 6, unscheduled intracyclic bleeding was reported by <20% of women in the 20 mg E4/LNG group (18.9%) and in the 15 mg E4/DRSP group (16.9%).Conclusion: This study showed that, of the four treatment modalities investigated, the 15 mg E4/DRSP combination has the most favourable bleeding pattern and cycle control.Implications: Due to its favourable bleeding pattern and cycle control, the 15 mg E4/DRSP combination is the preferred combination for further phase III clinical development. [ABSTRACT FROM AUTHOR]

Intrauterine adhesion (IUA), also known as Asherman's syndrome, is a common disease for among women. The extent of adhesion and pre-surgery hormone therapy greatly affects the function of uterine cavity. This current study investigates the association of different doses of estrogen before transcervical resection of adhesions (TCRA) surgery and clinical outcome in serious IUA. About 120 newly diagnostic serious IUA patients who underwent TCRA were randomly divided into three study groups: Estradiol valerate (progynova) 3 or 9 mg per diet before surgery and the control group. Follow-up hysteroscopy checkups were taken in 1- and 3-month post-operation. The effective power of 9 mg group was significantly higher than other groups. The 9 mg group achieved the best menstrual recovery rate in all study groups compared with the other two groups in 6 months post-operatively (p < 0.05). Our results confirmed estradiol valerateas an alternative effective drug for the prevention of IUAs before and after hysteroscopic surgery. [ABSTRACT FROM AUTHOR]

Background: Oral contraceptives are still associated with high discontinuation rates, despite their efficacy. There is a wide choice of oral contraceptives available, and the aim of this study was to assess continuation rates, bleeding profile acceptability, and the satisfaction of women in the first year of using a contraceptive pill containing estradiol valerate and dienogest (E2V/DNG) versus a progestogen-only pill (POP) in a real-life setting after discontinuing an ethinylestradiol-containing pill. Methods and results: In this prospective, noninterventional, observational study, 3,152 patients were included for the efficacy analyses (n=2,558 women in the E2V/DNG group and n=592 in the POP group (two patients fulfilled the criteria of the efficacy population, but the used product was not known). Women had been taking an ethinylestradiol-containing pill ≥3 months before deciding to switch to the E2V/DNG pill or a POP. Overall, 19.8% (n=506) of E2V/DNG users and 25.8% (n=153) of POP users discontinued their prescribed pill. The median time to discontinuation was 157.0 days and 127.5 days, respectively. Time to discontinuation due to bleeding (P<0.0001) or other reasons (P=0.022) was significantly longer in the E2V/DNG group versus the POP group. The E2V/DNG pill was also associated with shorter (48.7% vs 44.1%), lighter (54% vs 46.1%), and less painful bleeding (91.1% vs 73.7%) and greater user satisfaction (80.7% vs 64.6%) than POP use, within 3-5 months after switch. Conclusion: The E2V/DNG pill was associated with higher rates of continuation, bleeding profile acceptability, and user satisfaction than POP use and may be an alternative option for women who are dissatisfied with their current pill. [ABSTRACT FROM AUTHOR]

Background. Heavy menstrual bleeding (HMB) is a common gynecological complaint affecting quality of life. Objectives. To assess knowledge on diagnosis and treatments of HMB of Latin American (LA) obstetricians and gynecologists (OBGYNs). Methods. A survey was conducted during a scientific meeting, organized to provide updated information on topics of reproductive medicine to OBGYNs from 12 LA countries who were invited to respond to a multiple-choice questionnaire. Results. Of the 210 OBGYNs participating in the survey, from 169 (80.4%) to 203 (96.7%) answered the questions. Most respondents (80%) gave accurate answers regarding the amount of blood loss which defines HMB, underreported the proportion of women who consulted due to HMB, and were aware that the use of combined oral contraceptives (COCs) with ethynyl estradiol is not an adequate treatment in women with HMB. Female OBGYNs and those who worked in the private sector were more prone to report a higher possibility of improvement of HMB with a COC that contained estradiol valerate and dienogest or with a levonorgestrel-releasing intrauterine system. Conclusions. In general, the respondents were aware of the importance of HMB in gynecological practice and of the new medical treatments and underreported the proportion of women who consulted due to HMB. [ABSTRACT FROM AUTHOR]

Purpose: To compare symptomatic response in Indian women using different estrogen preparations for treatment of menopausal symptoms.Methodology: A randomized, single blind, four arm, parallel assignment study was conducted in VMMC and SJH, New Delhi, India. 200 Indian menopausal women were recruited and assigned into four treatment groups viz., estradiol valerate (E2V), conjugated equine estrogen (CEE), isoflavones and Placebo group. The statistical significance of categorical variables was determined by Chi-square, Fisher's exact test. In case of quantitative variable parametric test Student's t test was used. In case of quantitative variables where data are not normally distributed, Kruskal-wallis test and Wilcoxon Mann-Whitney test were used. Symptomatic response in vasomotor/vaginal symptoms was assessed in all groups.Results: Both E2V and CEE groups were effective in reducing severity and frequency of hot flashes. 91.9 % decrease was observed in mean hot flash score in the E2V group after 24 weeks of treatment, 89.2 % in the CEE group, 60.42 % decrease in the isoflavones group. While placebo led to 47.9 % decrease in mean hot flash score. After 24 weeks of therapy there was significant increase in vaginal health index in the E2V and CEE and the isoflavones group. No serious side effect was reported in any of the groups.Conclusion: Low doses of both CEE and E2V were equally effective for management of vasomotor/vaginal symptoms when administered over 24 weeks. However, it seems more reasonable to replenish with less costly and bio-identical hormone, i.e. micronized estradiol valerate which is equally effective.Trial Registry: The trial was registered under Clinical trial registry of India prospectively (number: CTRI/2012/04/002566). [ABSTRACT FROM AUTHOR]

Objectives: The menstrual cycle is characterised by cyclical fluctuations in oestrogens, progesterone and androgens. Changes in hormone levels in the premenstrual phase with the decline in progesterone trigger a physiological reaction which culminates in menstruation. This process is accompanied in many women by various symptoms such as pelvic pain, headache, mood disorders and gastrointestinal discomfort. The aim of this article was to summarise the latest findings on the physiology and pathophysiology of menstruation and review the impact of shortening the hormone-free interval (HFI) on the health and wellbeing of women.Results: Menstruation can be viewed as an inflammatory event in which local and systemic effects produce symptoms in genital and extragenital regions of the body. The mast cells are the main mediator of this reaction. In women using hormonal contraceptives, menstrual bleeding is not biologically necessary and it may be advantageous to maintain more stable levels of oestrogens, progesterone and androgens throughout the cycle. New combined oral contraceptives (COCs) have been formulated with a progressively shorter HFI (24/4 and 26/2) than traditional 21/7 pills, with the rationale of reducing hormone withdrawal- associated symptoms. Several studies have shown the beneficial effects of these regimens, which reduce the inflammatory exposure of the female organism and thus have the capacity to increase the quality of life of women. A combination of estradiol valerate (E2V) and dienogest (DNG) is administered on the shortest 26/2 regimen. This regimen has a broad evidence base from randomised controlled trials that have examined the impact of E2V/DNG on symptoms and quality of life.Conclusions: Shortening the HFI reduces the occurrence of bleeding-related inflammatory processes and subsequent physical and mental symptoms. The shortest interval with evidence of reproductive and sexual health benefits is provided by a 26/2 regimen. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder in women. Although many animal and human studies have been conducted, mechanisms involved in polycystic ovary formation and related metabolic dysfunction have not been fully understood,. Different techniques have been tried on animals to induce PCOS. Chronologically, the experimental methods used to induce PCOS included dehydroepiandrosterone application, estradiol valerate injection, fetal androgen administration, antiprogesterone (RU486) application and letrozole use. All of these models were described in this review article. [ABSTRACT FROM AUTHOR]

In the menopausal transition (MT), combined oral contraceptive (COC) should be chosen accordingly to its neutrality on liver metabolism and to its ability to counter the increase of fat mass (FM) that occurs in this reproductive period of life. This prospective multi-centric observational study was conducted on 36 women in their MT at the Universities of Cagliari, Modena and Naples. The body weight (BW), the Body Mass Index (BMI), the waist to hip ratio (WHR), the measurement of body composition (BC) with the Multi-frequency Bioelectrical Impedance (MF-BIA) were performed before, at the 6th and at the 12th month of the study in which a group of women (control group; N.18) did not assume COC, whereas the other 18 women assumed the four-phasic COC containing estradiol valerate (EV) associated with dienogest (EV/DNG group). In comparison to controls in the EV/DNG group, a significant decrease (p < 0.05) of BW (58.8 ± 7.6 to 57.3 ± 7.0), BMI (24.1 ± 2.7 to 23.5 ± 2.8), WHR (0.82 ± 0.052 to 0.79 ± 0.048) and FM (17.7 ± 5.4 to 16.4 ± 5.6) was observed. In controls, FM significantly increased (17.0 ± 11 to 17.7 ± 2.7;p < 0.05). In conclusion, these results suggest that the anti-androgenic and progestinic activities of DNG associated with a weak estrogenic activity of EV, is a contraceptive method capable of counteracting the negative changes of BC occurring in the MT. [ABSTRACT FROM AUTHOR]