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Fang Yang, Yuedan Xu, Xiangyu Li Department of Pharmacy, Shaoxing Keqiao Women & Children΄s Hospital, Shaoxing, Zhejiang, People’s Republic of ChinaCorrespondence: Xiangyu Li, Department of Pharmacy, Shaoxing Keqiao Women & Children΄s Hospital, Shaoxing, Zhejiang, 312030, People’s Republic of China, Tel +86-0575-85028228, Email 1070817321@qq.comAbstract: Severe drug eruption is a severe allergic reaction to a drug, usually due to irritation with certain drugs. It may be present as a generalized erythematous maculopapular rash, a pleomorphic rash, with or without blisters and ulcers. To the best of our knowledgeto date, there is no report of estradiol valerate-induced severe drug eruption. A case of rare severe drug eruption after taking estradiol valerate tablets was first reported to promote clinical drug safety management, especially for rare severe adverse reactions. Meanwhile, it is speculated that estrogen dermatitis might be associated with dendritic cell-mediated allergic mechanisms, inflammation-induced expression of estrogen receptor β, and elevated estrogen levels during pregnancy, according to previous studies. Therefore, pregnant women using this drug need to be focused on. Early and systemic use of glucocorticoids is beneficial to the outcome and prognosis of the disease. It highlights the need for clinicians to be vigilant about rare but serious adverse drug reactions, even with medications that are generally considered safe.Keywords: severe drug eruption, estrogen dermatitis, estradiol valerate, adverse drug reaction, pharmacovigilance

Abstract Objective This study aimed to assess the effect of sildenafil citrate and estradiol valerate as adjuvant therapy during ovarian stimulation cycles with clomiphene citrate in patients with unexplained infertility in Kisangani. Method A double-blind, randomized controlled trial was conducted for two years at two specialized health facilities in Kisangani (University Clinics of Kisangani and “Clinique des Anges Kisangani”). The population included 148 patients, 74 of whom were on clomiphene citrate + sildenafil citrate (CCSC) regimens and 74 of whom were on clomiphene citrate + estradiol valerate (CCEV) regimens for three months. The primary indicator was the conception rate, with secondary outcomes encompassing endometrial thickness, appearance and vascularity, the number of mature follicles and ovulation rate. Results The two groups were comparable in terms of sociodemographic and clinical characteristics. The mean duration of attempting to conceive was 4.39 years versus 4.36 years (P = 0.839), while the mean AFC was 11.51 versus 11.46 (P = 0.831), in the CCSC group versus CCEV group respectively. Secondary infertility was the most frequent diagnosis in each of the two groups. The biochemical pregnancy rate was comparable between the two groups (P = 0.385), while the clinical pregnancy rate was significantly higher in the CCSC group versus CCEV group (P = 0.04). Both perifollicular flow and the ovulation rate were significantly higher in the CCSC group versus the CCEV group (P = 0.006 and P = 0.002 respectively). However, endometrial vascularity/thickness, and the number of Graafian follicles were not significantly different between the two groups. Conclusion As an adjuvant, sildenafil increases the rate of clinical pregnancy more than does estradiol in patients with unexplained infertility undergoing ovarian stimulation with clomiphene citrate. Study registration PACTR 202,310,849,449,401 (Pan African Clinical Trials Registry).

Li Zhang,1,* Mupeng Li,1,* Lianlian Fan,1 Fangfang Liu,1 Peiwen Zhang,1 Qian Huang,1 Gang Mai,1 Jianzhong Shentu1,2 1Phase 1 Clinical Trial Center, Deyang People′s Hospital, Deyang, Sichuan, People’s Republic of China; 2Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianzhong Shentu, Email stjz@zju.edu.cn Gang Mai, Email stdygcp@163.comPurpose: Estradiol valerate (Progynova®) is used as hormone therapy to supplement estrogen deficiency. This study aimed to assess the bioequivalence of an estradiol valerate tablet and its generic form, under fasting and fed conditions.Methods: A randomized, open-label, single-dose, 2-period crossover study was conducted on healthy postmenopausal Chinese female volunteers under fasting and fed conditions. For each period, the subjects received either a 1 mg tablet of estradiol valerate or its generic. Blood samples were collected before dosing and up to 72 hours after administration. Plasma levels of total estrone, estradiol, and unconjugated estrone were quantified using a validated liquid chromatography-tandem mass spectrometry method.Results: A total of 54 volunteers were enrolled in this study. The primary pharmacokinetic parameters, including Cmax, AUC0-t, and AUC0-∞, were similar for the two drugs under both fasting and fed conditions, with 90% confidence intervals for the geometric mean ratios of these parameters, all meeting the bioequivalence criterion of 80– 125%. A total of 48 adverse events (AEs) were reported in the fed study compared with 24 AEs in the fasting study.Conclusion: Estradiol valerate and its generic form were bioequivalent and well tolerated under both fasting and fed conditions.Keywords: bioequivalence, estradiol valerate, postmenopausal, pharmacokinetics, safety

Ovarian steroidogenesis is an essential process that modulates reproduction. In the cyclic rat, vasoactive intestinal peptide (VIP) stimulates the secretion of steroid hormones, and this is dependent on the superior ovarian nerve (SON). In a rat model of polycystic ovarian syndrome induced by an estradiol valerate injection (PCOS-EV), the increase in SON activity results in elevated levels of norepinephrine (NE) and VIP in the ovary, which in turn leads to a rise in androgen. To analyze whether a greater influx of NE to the ovary, due to the hyperactivity of the SON, modifies the response of the gonad to VIP, PCOS-EV or vehicle-treated rats (Vh) were subjected to: 1) stimulation of the left or right ovary with VIP (L-VIP or R-VIP), or 2) the left or right section of the SON (LSON or RSON) followed by injection of VIP into the denervated ovary. Animals were euthanized 1 h later, and the serum levels of steroid hormones were assessed. In Vh rats treated on estrus, VIP stimulation increased the serum levels of testosterone, irrespective of the ovary injected (Vh L-VIP: 17.3 ± 0.5 or Vh R-VIP: 11.3 ± 1.1 vs. Vh: 6.4 ± 1.3). Section of the SON prior to VIP stimulation did not modify testosterone secretion (Vh LSNO+L-VIP: 15.5 ± 2.7 vs. Vh L-VIP: 17.3 ± 0.5; Vh RSNO+R-VIP: 10.6 ± 0.9 vs. Vh R-VIP: 11.3 ± 1.1). In PCOS-EV rats, VIP stimulation of the left ovary lowered testosterone (EV L-VIP: 11.0 ± 4.0 vs. EV: 24.6 ± 2.5). On the other hand, the effects of VIP injection into the denervated ovary were asymmetric, i.e., treatment in the left ovary not modified testosterone levels (EV LSNO+L-VIP: 6.3 ± 1.3 vs. EV L-VIP: 11.0 ± 4.0), while it decreased testosterone when performed in the right ovary (EV RSNO+R-VIP: 6.9 ± 1.3 vs. EV R-VIP: 29.6 ± 7.6). These results show that, in estrus, VIP has a stimulating effect on testosterone secretion, which is amplified by SON signals. Contrary to this, in the PCOS-EV rat, VIP lowers the elevated levels of androgens that characterize this animal model. Based on present results, we suggest that VIP could be used as a treatment for PCOS.

Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Current management strategies only provide symptomatic relief, and there is a need for better treatments. Gamma-oryzanol, a dietary component found in rice bran oil, has been shown to be effective in increasing insulin sensitivity, reducing weight, and alleviating oxidative stress. In modern Chinese medicine, 香格里拉谷维素胶囊, 纯净谷维素软胶囊, and 诺特博谷维素片 are some of the medicines marketed in China that contain gamma-oryzanol. This study aims to evaluate the effects of gamma-oryzanol on clinical hallmarks of PCOS. Also to compare the efficacy of gamma-oryzanol alone versus in combination with clomifene citrate. Methods: In this study, PCOS was induced in a rat model using estradiol valerate. Gamma-oryzanol was then administered both alone and in combination with clomifene citrate. Results: The effects of gamma-oryzanol on estrous cyclicity, fertility, histopathological alterations, estradiol and testosterone levels, and oxidative parameters were evaluated. The results showed that gamma-oryzanol, both alone and in combination with clomifene citrate, had protective effects against the estradiol valerate-induced PCOS rat model. The combination of gamma-oryzanol and clomifene citrate was particularly effective, showing significantly better results than the standard treatment group (clomifene citrate alone). Discussion: These results suggest that gamma-oryzanol could be used in combination with existing standard treatments to enhance the management of PCOS. However, further molecular and clinical studies are needed to confirm these findings.

The precise pathophysiology of polycystic ovary syndrome (PCOS) is not well-founded. In an attempt to fill this gap, the current study was executed to probe the effect of nanocurcumin (NCC) on ovarian tissue, in vitro fertilization (IVF) and pre-implantation embryo development in a mouse model of PCOS. Fifty adult female mice were randomly categorized into five equal groups including non-treated control and PCOS (receiving 0.20 mg estradiol valerate (EV) intraperitoneally once a day for 21 days) as well as NCC12.50 + PCOS, NCC25 + PCOS and NCC50 + PCOS (receiving respectively 12.50, 25.00 and 50.00 mg kg-1 NCC daily along with EV injection through oral gavages for 21 days) groups. Subsequently, ovarian histo-architecture and total anti-oxidant capacity, and malonaldehyde and catalase levels as well as in vitro fertilizing potential, early embryonic development and serum testosterone concentration were analyzed. Results showed that NCC in a dose-dependent manner improved ovarian cyto-architectural organization and oxidant/anti-oxidant balance along with IVF rate and pre-implantation embryo development in PCOS mice. These findings revealed that NCC at the doses of 25.00 and 50.00 mg kg-1 could alleviate PCOS-linked reproductive disruptions in female mice. [ABSTRACT FROM AUTHOR]

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]

Background: Polycystic ovary syndrome (PCOS) is an endocrine disease characterized by hyperandrogenism, hyperinsulinemia, followed by luteinizing hormone (LH) and follicle stimulating hormone (FSH) deficiency. PCOS conditions cause metabolic disorders that increase uric acid levels and malondialdehyde 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 BUN, creatinine, uric acid, and renal MDA levels. Methods: This research was an experimental designed study using Wistar rat (Rattus norvegicus) as animal model of PCOS which were divided into three groups: negative control (CN) group (n=6), Testosterone propionate induction group (n=6), and estradiol valerate 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 [Open Vet J 2023; 13(8.000): 1003-1011]

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]

Aim. To study the effect of combined oral contraceptives (COC) with estrogen identical to natural estrogen on the metabolic profile and body composition in females during the menopausal transition. Materials and methods. Females in the menopausal transition who needed contraception were divided into two groups. Group 1 (19 patients) received COCs containing estradiol valerate/dienogest (E2V/DNG) with a dynamic dosing regimen; Group 2 (19 patients) received monophasic COCs containing 17-estradiol/nomegestrol acetate (E2/NOMAC) for 6 months. Blood pressure (BP), parameters of carbohydrate and lipid metabolism, leptin, adiponectin, C-reactive protein, uric acid, and body composition by dual-energy X-ray absorptiometry were assessed initially and after the 6 months of therapy. Results. No significant changes in weight and body composition after 6 months of COC use were found in both groups. COCs with E2V/DNG had no significant effect on BP and all assessed metabolic parameters. Females taking COCs with E2/NOMAC showed increased fasting glucose of 4.85 (0.43) and 5.30 (0.37) mmol/L (p=0.002), insulin of 4.97 (2.35) and 8.82 (4.67) U/mL (p=0.012), NOMA index of 1.06 (0.54) and 1.88 (0.75); p=0.010 compared to baseline. However, the parameters remained within the reference values. Conclusion. COCs containing estrogens identical to natural estrogens do not affect body composition and have no significant adverse effect on BP and metabolic parameters in females during the menopausal transition, indicating that the use of these agents is acceptable from the perspective of their metabolic effects in this group of patients.

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. The present study aimed to evaluate the effects of Rosa damascena (RD) extract in estradiol valerate (EV) induced polycystic ovary syndrome rats. Methods: Adult female Wistar rats were divided into control (n = 12) and PCOS groups (n = 36). The PCOS model was induced using EV (4 mg/kg/day), which was confirmed in 6 rats in each control and PCOS group by observation of irregular estrous cycles in vaginal smears and ovarian multiple cystic. Then, the rest of the control group (n = 6) and PCOS rats (n = 30 in 5 divided groups) were treated orally for 28 days with metformin (MET) as a positive control (200 mg/kg/day) and RD extract (400, 800, and 1200 mg/kg/day, respectively). Body and ovary weights, biochemical and histological parameters, and expression of the IGF-1 gene were measured. Results: Compared to the PCOS group, metformin and higher doses of RD extract (800 and 1200 mg/kg/day) significantly reduced BW, HOMA-IR, FBS, FINS, TG, LDL, TT, E2, LH, TC, and liver enzymes, and increased HDL and FSH levels. In addition, ovarian weight and CFs decreased, and the findings showed an increment in PFs, CLs, PAFs, AFs, and GFs. IGF-1 gene expression levels were significantly decreased (p

Abstract Background Estrogen has been usually used in clinic for medical pretreatment of early pregnancy loss. There was little reported the effect of estrogen combined with prostaglandin analogs in the medical management of early pregnancy loss. This retrospective study aimed to evaluate the efficacy of estrogen pretreatment for medical management of early pregnancy loss and explore the confounding factor of intrauterine adhesion (IUA) on the outcome of medical management. Methods A total of 226 early pregnancy loss patients who received pretreatment with estradiol valerate and/or mifepristone, followed by carboprost methylate suppositories (study groups), or carboprost methylate suppositories alone (control group) in a regional central institution from March 2020 to February 2021 were retrospectively studied. All patients were evaluated by hysteroscopy 6 h after carboprost methylate suppositories use to assess whether the gestational sac was complete expulsion and assess the morphology of uterine cavity. Results The complete expulsion rate was 56.94% in the mifepristone and estradiol valerate-pretreatment group, 20.69% in the estradiol valerate-pretreatment group, 62.5% in the mifepristone-pretreatment group, and 12.5% in the control group. Compared with the control group, pretreatment with estradiol valerate did not increase the complete expulsion rate significantly (P = 0.297), pretreatment with mifepristone increased the complete expulsion rate significantly (P

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]

Abstract Introduction The hypothalamic-pituitary-ovarian (HPO) axis is the principal regulator of the reproductive system. The neurons in the arcuate nucleus of the hypothalamus signal the basophilic cells of the anterior pituitary to release luteinizing hormone (LH) and follicle stimulating hormone (FSH), which bind to the granulosa and theca cells of a follicle in the ovary to promote healthy follicular development. Disruption of this process at any time can lead to polycystic ovaries and, if left untreated, can lead to Polycystic Ovarian Syndrome (PCOS), one of the leading causes of infertility. A novel treatment option using 150 kHz Intermediate Frequency (IF) Electromagnetic Radiation (EMR) has been proposed to monitor the effect of this frequency during cystic development. Methods To prove this, an experiment was conducted to study the effect of whole-body exposure to 150 kHz EMR for 8 weeks at receptor, cellular, tissue and hormonal levels on the HPO axis of 25 young cyclic female rats. Results The results showed that 150 kHz EMR did not affect the histoarchitecture of neurons of arcuate nucleus of the hypothalamus of PCO-induced rats. It was also found that the number of basophilic cells of the pituitary gland was increased and the immunoreactivity of LH and FSH secretion increased. This EMR field also decreased the development of follicular cysts in the ovary and possibly increased the immunoreactivity of the LH and FSH receptors as well on the theca and granulosa cells of follicles in the ovary. Conclusion There are still many limitations to this study. If properly evaluated, the results of this experiment could help develop a new non-invasive treatment option for women with PCOS in the near future.

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]

Objective: Feminizing gender-affirming hormone therapy is the mainstay of treatment for many transgender and gender diverse people. Injectable estradiol preparations are recommended by the World Professional Association for Transgender Health Standards of Care 8 and the Endocrine Society guidelines. Many patients prefer this route of administration, but few studies have rigorously assessed optimal dosing or route., Methods: We performed a scoping review of the available data on estradiol levels achieved with various dosages of estradiol injections in transgender and gender diverse adults on feminizing gender-affirming hormone therapy. We also report on testosterone suppression, route (ie, subcutaneous vs intramuscular), and type of injectable estradiol ester as well as timing of blood draw relative to the most recent dose, where available., Results: The data we reviewed suggest that the current guidelines, which recommend starting doses 2 to 10 mg weekly or 5 to 30 mg every 2 weeks of estradiol cypionate or valerate, are too high and likely lead to patients having supraphysiologic levels across much of their injection cycle., Conclusions: The optimal starting dose for injectable estradiol remains unclear and whether it should differ for cypionate and valerate. Based on the data available, we suggest that clinicians start injectable estradiol cypionate or valerate via subcutaneous or intramuscular injections at a dose ≤5 mg weekly and then titrate accordingly to keep levels within guideline-recommended range. Future studies should assess timing of injections and subsequent levels more precisely across the injection cycle and between esters., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2024 AACE. All rights reserved.)

Abstract 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

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder, affecting women of reproductive age. Ageratum conyzoïdes (AGC) is used traditionally in the treatment of fever, rheumatism, and ulcer. This study investigates the effects of AGC on ovarian-uterine in PCOS rats. Methods: Female rats were randomized into four groups (n = 6). Group A control received 2 ml distilled water. Group B received a single dose of 4 mg/kg body weight (bwt) i.p estradiol valerate (EV). Group C received 500 mg/kg bwt AGC and group D received a single dose of 4 mg/kg bwt i.p EV followed by 500 mg/kg bwt AGC orally for 30 days. Parameters tested include follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2), progesterone (P), C-reactive protein (CRP), interleukin (IL)-6, IL-18 and tumor necrosis factor (TNF)- α, malondialdehyde (MDA), superoxide dismutase (SOD), Catalase (CAT), total protein (TP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and ovary and uterus histomorphometric. Results: Ageratum conyzoides decrease insulin resistance, obesity indices, TC, TG, LDL, MDA, T, LH, FSH, CRP, IL-6, IL-18, and TNF- α in PCOS rats. And increase HDL, E2, P, TP, CAT, and SOD in PCOS rats. AGC improved ovary and uterus histo-architecture, tertiary, and Graafian follicles, corpus luteum and endometrial thickness increased,and cystic and atretic follicles decreased. Conclusion: Ageratum conyzoides improved insulin sensitivity, antioxidant activities, hormonal imbalance, inflammatory makers, and histological changes in PCOS rats. Therefore AGC can be used as a potential adjuvant agent in the treatment of PCOS.

Background: Estrogen has been usually used in clinic for medical pretreatment of early pregnancy loss. There was little reported the effect of estrogen combined with prostaglandin analogs in the medical management of early pregnancy loss. This retrospective study aimed to evaluate the efficacy of estrogen pretreatment for medical management of early pregnancy loss and explore the confounding factor of intrauterine adhesion (IUA) on the outcome of medical management. Methods: A total of 226 early pregnancy loss patients who received pretreatment with estradiol valerate and/or mifepristone, followed by carboprost methylate suppositories (study groups), or carboprost methylate suppositories alone (control group) in a regional central institution from March 2020 to February 2021 were retrospectively studied. All patients were evaluated by hysteroscopy 6 h after carboprost methylate suppositories use to assess whether the gestational sac was complete expulsion and assess the morphology of uterine cavity. Results: The complete expulsion rate was 56.94% in the mifepristone and estradiol valerate-pretreatment group, 20.69% in the estradiol valerate-pretreatment group, 62.5% in the mifepristone-pretreatment group, and 12.5% in the control group. Compared with the control group, pretreatment with estradiol valerate did not increase the complete expulsion rate significantly (P = 0.297), pretreatment with mifepristone increased the complete expulsion rate significantly (P < 0.001). Pretreatment with mifepristone combined with estradiol valerate did not increase the complete expulsion rate significantly comparing with pretreatment with mifepristone (P = 0.222). The data of IUA showed that the complete expulsion rate in patients with IUA was lower than that in those patients without IUA (P < 0.001). Conclusions: Pretreatment with estrogen was not a sensible substitute for mifepristone in the medical management of early pregnancy loss. Mifepristone followed by carboprost methylate suppositories was likelihood of the ideal medical scheme in early pregnancy loss. IUA decreased the complete expulsion rate of medical management, it is cautious about medical management for early pregnancy loss with risk of IUA. Trial Registration Number: ChiCTR2100046503. Date of registration (retrospectively registered): May 18, 2021. Trial registration website: http://www.chictr.org.cn/. [ABSTRACT FROM AUTHOR]

Context: Limited studies have compared the effects of combined oral contraceptives (COCs) containing natural estrogens and synthetic ethinylestradiol (EE) on reproductive hormones. Objective: To compare estradiol valerate (EV) + dienogest (DNG), EE + DNG, and DNG alone (active control) on levels of follicle stimulating hormone (FSH), luteinizing hormone, anti-Müllerian hormone (AMH), ovarian steroids, sex hormone binding globulin (SHBG), and the free androgen index (FAI). Methods: This spin-off study from a randomized trial enrolled 59 healthy, 18 to 35-year-old ovulatory women, outpatients at Helsinki and Oulu University Hospitals, Finland, who were randomized to EV 2 mg + DNG 2-3 mg (n = 20); EE 0.03 mg + DNG 2 mg (n = 20); and DNG 2 mg (n = 19) for 9 weeks. Blood samples were drawn at baseline, and at 5 and 9 weeks. Age and BMI were comparable between groups; 3 women discontinued. Results: EV + DNG suppressed FSH by -27% (-51% to -3%) (median [95% CI]) vs EE + DNG, -64% (-78 to -51), P = 0.04, but AMH levels decreased similarly by -9% (-18 to -0.1) vs -13% (-28 to 0.2), P = 0.38, respectively. EV + DNG increased SHBG levels by 56% (30% to 82%) and EE + DNG by 385% (313% to 423%), P < 0.001. Total testosterone decreased by 16% (-27% to -5%) in the EV + DNG group but it did not decrease in the EE + DNG group, whereas the FAI decreased by -39% (-54% to -25%) vs -72% (-78% to -67%), P < 0.001. DNG alone did not induce changes in any of these parameters. Conclusion: Compared with EE + DNG, treatment with EV + DNG resulted in milder pituitary downregulation and reduced induction of hepatic SHBG synthesis--potentially carrying more beneficial health effects. [ABSTRACT FROM AUTHOR]

The review presents the psychosocial characteristics of young women in todays millennial generation and survey data regarding their hormonal contraceptive requirements. The results of randomized clinical trials and real-life studies of the use of the combined oral contraceptive (COC) Qlaira containing estradiol valerate and dienogest (E2V/DNG) in a dynamic dosing regimen were analyzed, in which the reliability of the contraceptive effect of the drug was identified and confirmed, the restoration of fertility was population level after drug withdrawal, its minimal effect on metabolism and a reduced risk of cardiovascular complications (venous and arterial thrombosis) when using Qlaira COC in comparison with other COCs. The absence of a negative effect of COC E2V/DNG on body weight, sexual function and vaginal microbiocenosis in most women has been proven. The data on satisfactory characteristics of menstrual bleeding (lighter and shorter) in users of Qlaira COC and a decrease in symptoms associated with a hormone-free interval, which often occur when taking other COCs in the 21/7 regimen, are presented. The favorable efficacy and safety profile of COC E2V/DNG in real conditions, the advantages of estrogen bioidentical to the endogenous, in the composition of the drug, the dosage regimen 26/2, the positive effect on the lifestyle, determine the significant satisfaction of young women, including young women with children, and the ability to use the drug for a long time until menopause.

Abstract 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

ABSTRACT: Hematology and serum biochemistry study may provide antique knowledge about the physical status of individuals, making them a valuable tool to differentiate healthy animals from affected animals. We aimed to investigate Steroid safety levels in birds through ex-situ studies at regular therapeutic doses. A total of 100 birds were used for hematology and serum biochemistry. This study was designed into 2 trials over the summer and winter, each comprised 5, 10, 15, and 20 d. Each study group was based on 5 control group birds and 20 experimental group birds. A sum of 2 groups representing 2 different steroids trial groups was treated with therapeutic doses to the stretch of 5, 10, 15, and 20 d each season. A therapeutic dose of each of the steroids was given at the rate of 3 drops 2 times a day to each bird. Analysis of data reveals that steroids had severe effects on bird's (Coturnix coturnix) hematological parameters. In most trials, the hematological effects of bromocriptine as mesylate showed an increase in red blood cell count and white blood cell count. On the other hand, steroid estradiol valerate showed a decrease in these parameters. Effect of steroids on serum biochemistry profile indicate acute damage to vital organs, especially to liver and kidney, indicating an increase in cholesterol, total protein, albumin, urea, and uric acid. The overall effect of steroids on the bird's serum and biochemistry of quails were nearly similar but different only in their intensity.

Background: Estradiol valerate (EV) is known to cause hypothalamic-pituitary dysregulation of the gonadotrophin-releasing hormone. This study focused on the impact of aqueous extract of Solanum melongena (SM) on EV-induced ovarian-pituitary dysfunction in female Sprague-Dawley rats. Methods: Thirty-two healthy female Sprague Dawley rats weighing (8 weeks old; weight 150–200 g) were randomly divided into four groups of eight (n = 8) rats each. Group A received 2 ml of distilled water, Group B received a single dose of 4 mg/kg body weight (bwt) of EV (i.p), Group C received 500 mg/kg bwt SM extract orally and Group D received a single dose of 4 mg/kg bwt of EV (i.p) and 500 mg/kg bwt of SM orally, the experiment lasted for 21days. The following parameters body weight, pituitary gland weight, ovary weight, ovary, and pituitary gland histomorphology, total antioxidant status (TOS), total oxidant status (TOS), oxidative stress index (OSI), total cholesterol (TC), triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein (HDL), progesterone, FSH, LH, Testosterone, and estradiol were assessed. Results: Estradiol valerate decreases the number of healthy follicles, progesterone, estradiol, HDL, and TAS. And increase degenerated cystic follicles, TT, FSH, LH, triglyceride, TC, LAL, TOS, and OSI. Pituitary gland showed degenerative changes, characterized by neutrophil infiltrations and loss of cellular projections marked improvement was observed in the ovary, pituitary gland, hormone, and biochemical parameters after SM administration. Conclusion: Solanum melongena offers protection against EV-induced ovarian-pituitary dysfunctions evidence by restoration of oxidative stress markers, steroidogenesis, and histopathological alterations back to control level.

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]

Description. The review is presented by modern publications, reflecting the importance of high-quality patient counseling when choosing a method of contraception and the factors that influence it. The choice of combined oral contraceptive (COC) is determined by the need for reliable and safe contraception, expectations for an improved quality of life, and doubts about the frequency of side effects and effects on reproductive and somatic health. Modern COCs containing natural hormone (estradiol valerate), a new gestagen (dienogest) with a dynamic regime and a shortened hormone-free interval (2 days) satisfy the COC requirements of most women from menarche to menopause when contraception is required. An improvement in the profile of menstrual bleeding (a decrease in blood loss in 88% of users) and sexual functioning (increased libido, arousal, and maintaining the cyclical nature of sexual behavior) has been shown. Estradiol valerate does not affect metabolism, has a low risk of thromboembolic events (the adjusted risk of venous thromboembolism compared to other COCs is 0.4) and a low frequency of failure due to side effects (1.7%). This tool is characterized by high efficiency (adjusted Pearl index 0.42) and user satisfaction (78.180.2%). Conclusion. COCs with estradiol valerate/dinogest in 26/2 mode, fully satisfying the requirements of women for contraception, contributes to high adherence to it, that is, consistent and correct use, which contributes to the long-term use of the selected COC and ensures the quality of life of women for many years.

By definition, contraception is the prevention of pregnancy and infection from diseases by mechanical, chemical and other contraceptives and methods. According to World Health Organization (WHO) statistics, up to 40% of women of reproductive age still believe that their needs for family planning services are not met during counseling. When recommending contraception, it is important to consider: the characteristics of the potential consumer, the underlying risk of the disease, possible undesirable drug reactions of various drugs, the cost, availability and preferences of the woman herself. Women are often forced to abandon the use of a contraceptive method in connection with adverse events, for example, when using combined oral contraceptives (COCs), they may feel worse (headaches, mood lability, weight gain, swelling, decreased libido) in a hormone-free interval, especially with the reception mode 21/7. Lack of contraception can lead to an increased risk of an unwanted pregnancy. According to statistics in the Russian Federation in 2018, the absolute number of abortions amounted to 567 183, which, according to the UN classification, corresponds to the average level (level of abortion rate per 1000 women of childbearing age). According to clinical practice, there is a relationship between deterioration of well-being and the duration of the hormone-free interval. At the moment, in our country there is the only COC, which has a hormone-free interval of 2 days, containing bioidentical estrogen estradiol valerate and dienogest. According to the Cochrane Library, COCs with a short hormone-free interval are most effective in relation to the clinical manifestations of the estrogen withdrawal syndrome. WHO calls on clinicians to raise womens awareness of modern methods of contraception.

Objective To investigate the effect of estradiol valerate (E2V) on endometrial receptivity induced by clomiphene in polycystic ovary syndrome (PCOS) rats. Methods Rats were divided into control group (administered 0.9% sodium chloride solution), and PCOS model group (administered 50 mg/kg clomiphene), E2V low, medium and high-dose intervention group [administered (0.2, 0.5, 1.0)mg/kg E2V+50 mg/kg clomiphene]. Serum sex hormone level was compared. Morphological change of endometrium was examined by ELISA. The expression of estrogen receptor (ER), progesterone receptor (PR), homeobox gene (Hox)A10, empty ventilator homeobox (Emx)2, integrin αvβ3 mRNA and protein in the endometrium were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot. Results Compared with the control group, luteinizing hormone/follicle-forming hormone (LH/FSH), testosterone (T), relative expressions of Emx2 mRNA and protein were significantly increased (P＜0.05), while estradiol (E2) level, glandular area, glandular area, endometrial thickness and glandular/interstitial area ratio, relative expressions of ER, PR, HoxA10, integrin αvβ3 mRNA and protein were significantly decreased (P＜0.05). Compared with PCOS model group, the changes of above indexes in E2V low, medium and high-dose intervention group were opposite (P＜0.05). Conclusions E2V can improve endometrial receptivity of PCOS clomiphene-induced ovulation rats. E2V is potentially related to the up-regulation of ER, PR, HoxA10, integrinαvβ3 and down-regulation of Emx2.

Objective: To assess the estrogenic activity of hydroalcoholic extract of Clitoria ternatea leaves in female Wistar rats. Methods: Hydroalcoholic extract of C. ternatea leaves prepared by using cold maceration method was tested for estrogenic activity. An acute toxicity study was conducted to estimate the safe dose using OECD 423 guidelines. For estrogenic activity, ovariectomized female rats were divided into four groups, with 6 rats in each group. The control and standard groups were administered with 1% carboxymethyl cellulose orally and estradiol valerate at 1 μg/rat/day subcutaneously, respectively. The third group was administered with hydroalcoholic extract of C. ternatea at the dose 500 mg/kg body weight orally and the fourth group was administered with hydroalcoholic extract of C. ternatea at the dose 500 mg/kg body weight orally along with estradiol valerate at dose 1 μg/rat/day subcutaneously. All treatments lasted for 7 consecutive days and estrogenic activity was assessed by observing vaginal cornfication. On day 8, all animals were sacrificed and uterine horns were dissected out. Utrine weight was measured and blood serum was further processed for the estimation of biochemical parameters like cholesterol, total proteins, alkaline phosphatase and estrogen by autoanylser. Histological studies of uterus were also carried out. Results: Acute toxicity studies indicated the hydroalcoholic extract of C. ternatea leave was found to be safe up to the dose level of 2 000 mg/kg. Oral administration of C. ternatea extract at the dose 500 mg/kg body weight and and estradiol valerate (1 μg/rat/day) caused morphological changes i.e. increase in uterine weight, vaginal opening and cornification of cells; biochemical changes i.e. increase in cholesterol, total protein, alkaline phosphatase and estrogen contents; histological changes i.e. increase in uterine diameter, thickness and height of endometrium. Simultaneous administration of C. ternatea extract with estradiol valerate showed a synergistic effect. Histological investigations further confirmed the strong estrogenic nature of C. ternatea extract. Conclusions: C. ternatea extract (500 mg/kg) showed a significant estrogenic activity which is also supported by biochemical and histological studies. So, on the basis of these findings, it can be concluded that C. ternatea can be used as an alternative to synthetic oral contraceptives.

Background: Both sildenafil and estradiol are seen to improve endometrial thickness in patients with infertility who are undergoing clomiphene induction cycles. However, the correlation between endometrial thickness and pregnancy rate is debatable. This study investigated the effect of adding oral sildenafil to clomiphene citrate (CC), compared to adding estradiol valerate, on the uterine biophysical profile (Applebaum score) and pregnancy rate., Methods: This was a double-blinded, randomized controlled trial conducted in Kisangani in the Democratic Republic of the Congo from October 1, 2021, to October 31, 2023. Patients with unexplained infertility were randomly assigned to one of two groups: the interventional, which was given CC (2 x 50 mg/day from day 3 to day 7 of the menstrual cycle) + sildenafil (2 x 25 mg/day orally from day 8 to day 12) or (ii) the control group, which was given CC (similar dosage as the intervention group) + EV (2 x 2 mg/day orally from day 8 to day 12), for a maximum of three cycles. Applebaum scores and clinical pregnancy rates were measured., Results: Patients in the sildenafil and EV groups were similar in mean age (29.04 versus 28.89 years). Of the 74 patients enrolled in each group, 71 in the sildenafil group and 72 in the EV group received treatment and were followed to completion. The Applebaum scores were significantly higher in the sildenafil group than in the EV group (17.05 versus 15.14, respectively, P=0.000). In the sildenafil group, the clinical pregnancy rate was also significantly higher, at 28.92% versus 20.83% in the EV group (P = 0.04)., Conclusion: As compared to EV, the oral addition of sildenafil to CC is associated with a good Applebaum score and a high rate of clinical pregnancy in patients with unexplained infertility., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of the University of Kisangani issued approval UNIKIS/CER/08/2021. The study was conducted in accordance with the declaration of Helsinki. Patients were provided with explanations of the study's objectives and procedures prior to participation. The trial was registered in the Pan African Clinical Trials Registry with registration number: PACTR202310849449401. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This study was financially supported by a grant from the Faculty of Medicine and Pharmacy of the University of Kisangani and the Fondation des Anges. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bosenge-Nguma et al.)

Objective: This study aimed to determine the most appropriate age for height control treatment in patients with Marfan syndrome (MFS). Materials and Methods: This retrospective study included patients with MFS who underwent height control treatment with estradiol valerate. The estrogen dose was increased according to the height change. The cut-off age for the maximum difference between the expected height and actual final height was evaluated. Results: Seventeen patients were included in this study. The difference between the height predicted by the growth curve and the final height (gcHtD) and that predicted by the bone age and the final height (baHtD) was the largest in the 10.5 years age group (p=0.0045 and p=0.0237, respectively). The gcHtD was 10.6 (10.2, 13.5) cm for patients aged ≤10.5 years, whereas it was 0.6 (−3.65, 5.85) cm for patients aged >10.5 years. The baHtD was 10.1 (7.31, 11.42) cm for patients aged ≤10.5 years, while it was 3.83 (0.84, 6.4) cm for patients aged >10.5 years. When height change was observed for a minimum of 6 months after completion of estrogen treatment, the average growth was 0.6 (0.2, 2.1) cm. Conclusion: Initiating height control treatment before the age of 10.5 years is effective in female patients with MFS. [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]

To explore the clinical therapeutic effect on premature ovarian failure (POF) treated with the combination of mild moxibustion and western medication. A total of 66 patients were divided into a control group and an observation group according to random number table, 33 cases in each one. In the control group, the conventional western medication was administered. In the observation group, besides the treatment as the control group, mild moxibustion was supplemented at Guānyuán (关元CV4), Qìhăi (气海CV6), Píshū (脾俞BL20) (bilateral) and Shènshū (肾俞BL23) (bilateral). The duration of treatment was 3 menstrual cycles in either group. Before treatment and on the 9th day of menstruation after 3-menstrual cycle treatment, the number of antral follicles and ovarian volume were detected by color Doppler ultrasound respectively. Before treatment and on day 2 to 4 of menstruation after 3-menstrual cycle treatment, the levels of serum estrogen (E 2), follicle-stimulating hormone (FSH), interleukin-21 (IL-21) and vascular endothelial growth factor (VEGF) were determined separately and the therapeutic effect was evaluated in two groups separately. The effective rate was 93.94% in the observation group and was 72.73% in the control group (P < 0.05). After treatment, the number of antral follicles and ovarian volume were increased as compared with those before treatment in the patients of two groups (both P < 0.05). After treatment, the number of antral follicles and ovarian volume in the observation group were higher than the control group (both P < 0.05). After treatment, the levels of serum E 2 and FSH were improved as compared with those before treatment in the two groups (both P < 0.05). The levels of serum E 2 and FSH in the observation group were better than the control group after treatment (both P < 0.05). The levels of serum IL-21 and VEGF after treatment did not change obviously as compared with those before treatment in the control group (both P > 0.05). But in the observation group, the levels of serum IL-21 and VEGF after treatment changed apparently as compared with those before treatment (both P < 0.05) and the levels of these two indicators after treatment were better than the control group (both P < 0.05). The combined treatment of mild moxibustion with western medication achieves the definite therapeutic effect on POF and it increases the number of antral follicles and ovarian volume and regulates sex hormone level, which is probably related to the regulation of serum IL-21 and VEGF. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aimed to determine the most appropriate age for height control treatment in patients with Marfan syndrome (MFS).Materials and MethodsThis retrospective study included patients with MFS who underwent height control treatment with estradiol valerate. The estrogen dose was increased according to the height change. The cut-off age for the maximum difference between the expected height and actual final height was evaluated.ResultsSeventeen patients were included in this study. The difference between the height predicted by the growth curve and the final height (gcHtD) and that predicted by the bone age and the final height (baHtD) was the largest in the 10.5 years age group (p=0.0045 and p=0.0237, respectively). The gcHtD was 10.6 (10.2, 13.5) cm for patients aged ≤10.5 years, whereas it was 0.6 (−3.65, 5.85) cm for patients aged >10.5 years. The baHtD was 10.1 (7.31, 11.42) cm for patients aged ≤10.5 years, while it was 3.83 (0.84, 6.4) cm for patients aged >10.5 years. When height change was observed for a minimum of 6 months after completion of estrogen treatment, the average growth was 0.6 (0.2, 2.1) cm.ConclusionInitiating height control treatment before the age of 10.5 years is effective in female patients with MFS.

Abstract This study aimed to investigate the effects of the combined injectable contraceptive (CIC) containing estradiol valerate (EV) and norethisterone enanthate (NET-EN) on aorta function and morphology, as well as on redox status, of female Wistar rats. Female rats (9-10 weeks of age) received intramuscular injections of CIC (0.1 mg EV plus 1 mg NET-EN) or castor oil (control group, CTL) for 8 weeks, once a week. Food intake, body weight and systolic blood pressure were measured during the treatment period. Thoracic aortic segments were prepared for isometric tension recording and morphological analysis. Redox status was evaluated by total oxidant status (TOS) and lipid peroxidation (LP) on plasma and reduced glutathione (GSH) on whole blood. CIC group presented lower food intake and lower total weight gain compared to CTL group. There was no change in systolic blood pressure, vascular response of aorta to phenylephrine and acetylcholine and aorta thickness. Plasma TOS and LP values were reduced in CIC group, although GSH was not altered. It was shown that the long-term treatment with the CIC containing EV plus NET-EN does not induce endothelial dysfunction and histomorphometric changes of vascular wall, as well as improves redox status on female Wistar rats.

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]

Objective: To determine the benefits of COC in the 26/2 mode compared with the traditional 21/7 in reducing the frequency of side effects. Main provisions. Side effects – the main cause of women’s refusals to take COCs – occur predominantly on days of taking pills without hormones due to a drop in estradiol levels. Reduction of the hormone-free COC interval (mode 26/2) reduces the frequency of headache and pelvic pain and other symptoms. Conclusion. COC, with regimen 26/2, may be a promising option for users who experience adverse symptoms.

Franca Fruzzetti,1 Anna Maria Paoletti,2 Tiziana Fidecicchi,1 Giulia Posar,1 Riccardo Giannini,3 Marco Gambacciani11Department of Obstetrics and Gynecology, Pisa University Hospital, Pisa, Italy; 2Department of Obstetrics and Gynecology, Cagliari University Hospital, Cagliari, Italy; 3Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, ItalyPurpose: The aim of the study was to examine the discontinuation rate of hormonal contraception with estradiol valerate (E2V) and dienogest (DNG).Patients and methods: We collected data at the Family Planning Clinics of the Departments of Obstetrics and Gynecology of Pisa and Cagliari. We included in the analysis 354 consecutive women using oral contraceptive pills containing E2V and DNG. We analyzed the rate and the reason for discontinuation, classifying the reasons in 5 categories: 1) minor side effects, 2) adverse events, 3) other events not directly caused by the drug or conditions for which the pill could represent a risk factor, 4) no compliance with the method and 5) no further need.Results: Of the 354 women examined, 50.8% had discontinued E2V/DNG pill. Excluding women who stopped the pill because of no further need (10.5%), 27.4% discontinued because of minor side effects, 1.7% discontinued for adverse events, 9.9% because of other events not directly caused by the drug or conditions for which the pill could represent a risk factor and 1.4% because of difficulties with compliance. Irregular bleedings were the main reasons reported for discontinuation. The time to discontinuation for irregular bleedings was significantly (p

Taking into account that the frequency of abortions in Russia today remains quite high, the strategy of fertility regulation through the provision of contraceptive advice to women of various ages comes to the fore. It has been proven that combined oral contraceptives are the most effective method of preventing unwanted pregnancies. An innovative combination of oral contraceptives containing estradiol valerate (EV) and dienogest (DNG) dynamically provides effective inhibition of ovulation and sufficient cycle control. DNG/EV has high efficacy, acceptability and tolerability and can be successfully used in sexually active women in need of contraception, regardless of their age. Like any modern contraceptive, this drug possesses a whole arsenal of pronounced therapeutic possibilities, which can be used in real clinical practice. In addition, the combination of EV and DNG is highly effective in the therapy of menorrhagia. The percentage of patients who had successful treatment and resulted in a decrease in menstrual blood loss was high. The effectiveness of the drug is confirmed by the bleeding of withdrawal at the end of the first treatment cycle and continues to increase gradually with further administration.

The purpose of the review: presentation of modern data on the pathogenesis of abnormal uterine bleeding (AMC) without anatomical substrate (ovulatory, endometrial, coagulopathic) and the effectiveness of their treatment with medication.Basic provisions. Information on the pathogenesis of AMC not associated with structural abnormalities of the uterus is presented. It was shown that non-hormonal drugs have similar efficacy. Among the hormonal agents, levonorgestrel-containing intrauterine system (IUD-LNG) and estrogen-progestogen preparations (combined oral contraceptives, COCs) favorably differ. COCs recover an acute episode of AMC in 66.8% of cases (according to some data – in 88%), which is higher in comparison with non-hormonal drugs; in chronic cases – reduce blood loss by 88% (after 6 months of therapy), and are not inferior in effectiveness to intrauterine devices with levonorgestrel (83% after 3 months of therapy).The conclusion. Thus, non-hormonal drugs have similar efficacy in arresting AMC without an anatomical substrate, but are inferior to COCs. In case of chronic AMC, the first-line drugs are IUD-LNG and COC containing E2B / NNG, which contribute to the normalization of the menstrual cycle and the volume of menstrual blood loss with proven efficacy.

Franca Fruzzetti,1 Angelo Cagnacci2 1Department of Obstetrics and Gynaecology, Santa Chiara Hospital, University of Pisa, Pisa, Italy; 2Institute of Obstetrics and Gynecology, Department of Medical Area, University of Udine, Udine, Italy Objective: Estradiol (E2)-based hormonal contraceptives impact less than ethinylstradiol (EE) contraceptives on venous thromboembolism (VTE) in comparison to formulations with EE.Study design: In this article, the pharamacologic data of EE and E2 were briefly reviewed, along with the induced biologic effect. These data were then related to a recent large international prospective, controlled, non-interventional cohort active surveillance study, on the cardiovascular risk of users of different types of combined estro-progestin contraceptive (CEPC).Results: The crude HR for E2-valerate (E2V)/dienogest vs other CEPCs with EE was 0.8 (95% CI, 0.4–1.6), but when the data were corrected for age, body mass index, duration of use, and family history of VTE, the corresponding adjusted HR was 0.5 (95% CI, 0.2–1.0). A comparison of the E2V/dienogest and EE/levonorgestrel groups showed that the two contraceptives induced a similar VTE risk with the crude and adjusted VTE HRs of 0.7 (95% CI, 0.3–1.8) and 0.5 (95% CI, 0.2–1.3), respectively. Similar results were obtained when the observation was prolonged to January 2017.Conclusions: The reduced impact of E2 vs EE on coagulation translates into the epidemiologic evidence of a reduced number of events in E2V vs EE users, when progestins other than levonorgestrel are used. However, E2 may continue to negatively impact on the risk of VTE, and this should not be forgotten at the time of prescription. Family history of VTE or thrombophilia, age, and obesity are risk factors for VTE too. If these risk factors are not taken into consideration and excluded, they can overcome or hide the higher safety of E2 vs CEPCs with EE. Keywords: estradiol, estradiol valerate, contraception, venous thromboembolism, dienogest

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]

Endometrial thickness (ET) is one of the best predictors of implantation rate and pregnancy success rate because endometrial growth depends on hormones. Estrogen regulates the proliferative phase, endometrial proliferation induced by estrogen after menstruation is largely dependent on blood flow to the basal endometrium that produces progesterone receptors which are required for progesterone-regulated endometrial growth in the secretory process. To compare the effect of estradiol valerate vs. sildenafil citrate on endometrial receptivity and subsequent pregnancy outcome in unexplained infertility patients receiving letrozole for ovulation induction. Herein, 21 patients with unexplained infertility underwent ovulation induction by letrozole (2.5 mg). Patients were divided into 2 groups; group A (10 patients) were given sildenafil tablets vaginally (25 mg) four times daily and group B (11 patients) were treated with estradiol valerate tablet 2 mg/12 hours. Patients were evaluated by transvaginal ultrasonography (TVS) to determine endometrial thickness, pattern, size, and the number of the dominant follicles, serum assessment of Vascular Endothelial Growth Factor (VEGF) level at trigger day, and chemical pregnancy outcome 14 days later. Results showed that the endometrial thickness, patterns of the endometrium, VEGF, size of the dominant follicle at the trigger day, and pregnancy rates were not significantly different between the two groups. However, the difference in the number of the dominant follicles at trigger day was statistically significant which is more in the sildenafil treated group. The present study confirmed the findings of both Sildenafil and E2 valerate to boost endometrial receptivity and pregnancy rate. [ABSTRACT FROM AUTHOR]

Estradiol valerate (EST) and Norethisterone acetate (NOR) are co-formulated as a hormone replacement therapy. Naturally occurring steroidal hormones like estradiol, estrone and estriol are also considered as impurities in drug substance. Chromatographic separation of these five steroidal hormones was developed by HPLC and TLC. Reversed-phase chromatography was applied using either acetonitrile–methanol containing 0.05% β-cyclodextrin as a mobile phase for HPLC with gradient elution and chloroform–propanol–formic acid (5:3:2, by volume) as a developing system in TLC. The methods have been applied for determination of EST and NOR in presence of other natural congeners in biological samples as well as in drug products as official impurities. Solid-phase extraction was applied for saliva sample cleaning using testosterone as internal standard whereas ampoules and tablets formulations were used in pharmaceutical applications. The methods have been validated for bioanalytical and pharmaceutical analysis following the respective FDA and ICH guidelines. The obtained results were statistically compared with the official methods for both drugs. [ABSTRACT FROM AUTHOR]