Estradiol Valerate Research Articles (Page 1)

Inducing agents and PCOS - A comprehensive analysis.

Disclosure: R. Lassalle Klein: None. R. Feinn: None. P. Phulwani: None.Guidelines list oral estrogen tablets, transdermal patches, and intramuscular (IM) injections as acceptable modalities to offer patients who desire feminization using estrogen.1 Data suggests a higher risk of liver enzyme elevation and thrombotic events with oral estrogen versus other modalities, presumably due to the first pass effect.2 Side effects of other therapies are barriers to satisfactory treatment. The aim of this study was to examine the efficacy and safety of self-administered weekly subcutaneous (SC) injections of estradiol in a retrospective case series of adult transgender women. 40 patients who met 6 inclusion criteria were assessed: age ≥18 years old, received diagnosis ICD10 F64.0 (gender dysphoria/incongruence), prescribed estrogen formulation was solely SC estradiol cypionate or estradiol valerate, visited Hartford Healthcare Endocrinology between January 1, 2020 and March 7, 2023, completed at least two lab visits to establish baseline and also after initiation of therapy, and had at least one clinic visit to assess satisfaction. RedCAP was used to collect, de-identify, and analyze data from patient charts on retrospective review. The majority (N=27, 67.5%) achieved the target-range estradiol (100-300 pg/uL) using SC estradiol cypionate or valerate within the study period. With respect to the in-range patients who were using estradiol cypionate (N=6) the commonest dose was 2.5 mg/week (mean= 3.2 ± 1.1). No patients at or below dosages of estradiol cypionate of 1 mg/week or estradiol valerate 2 mg/week achieved target-range. With respect to the in-range patients who were using estradiol valerate (N=21), the commonest dose was 4 mg/week (mean 5.38 ± 2.0). Remaining patients out of range at the conclusion of the study continued dose titration. Blood estradiol level correlation with AST/ALT was analyzed using a two-tailed t-test. The correlation between estradiol level and AST was r = 0.156 (p=0.414) and correlation between estradiol level and ALT was r = 0.088 (p=0.644), which were both small and not statistically significant. In this study, including in patients with high estradiol levels (estradiol range: 21-991 pg/uL), no elevated liver enzymes or adverse events occurred in relation to therapy. Although this is a small, retrospective, and short duration study, it highlights that SC estradiol is likely a safe option for estrogen replacement for gender affirming hormone therapy and has potentially broader applications for all conditions that require estrogen. 1. Hembree WC et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017 Nov 1;102(11):3869-3903. 2. Getahun D et al. Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons: A Cohort Study. Ann Intern Med. 2018 Aug 21;169(4):205-213.Presentation: Sunday, July 13, 2025

The effects of metformin and sitagliptin for polycystic ovary syndrome treatment are enhanced by combining them.

The leaves of Linzia gerberiformis are used in traditional Cameroonian medicine for the treatment of respiratory infections and hepatitis. The present study was conducted to evaluate the anti-amnesic effects of the aqueous extract of L. gerberiformis leaves in ovariectomized rats exposed to chronic unpredictable mild stress (CUMS). A total of 42 female rats were used for this study. Thirty five ovariectomized rats were subjected to chronic unpredictable mild stress, distributed across five treatment groups, while 7 non-ovariectomized rats served as a control group receiving distilled water and were labeled as the vehicle. Ovariectomized (OVX) female rats exposed to CUMS for 1 week were treated with distilled water, estradiol valerate (1mg/kg), and the aqueous extract of L. gerberiformis leaves (75, 150, and 300mg/kg) for 14 days starting from the 8th day after OVX. Memory integrity was assessed using the novel object recognition test (NORT) and the Morris water maze test (MWM). Hippocampus was collected to assess the cholinergic system [acetylcholinesterase (AChE) and acetylcholine], pro-oxidants (nitric oxide (NO) and malondialdehyde (MDA)), anti-oxidants (superoxide dismutase (SOD), catalase, and, GSH (reduced glutathione)) as well as 17-β-estradiol. Plasma was also collected to measure the concentration of 17-β-estradiol. The aqueous extract of L. gerberiformis leaves at 75mg/kg and 150mg/kg improved short-term recognition memory and long-term spatial learning memory compared to OVX animals exposed to CUMS treated with distilled water. The aqueous extract of L. gerberiformis leaves increased plasma and hippocampal 17-β-estradiol compared to OVX + CUMS animals. In addition, L. gerberiformis significantly prevented the effect induced by the combined action of ovariectomy and CUMS in rats by preventing the decrease of estrogen, acetylcholine, SOD, CAT and GSH; and the increase in AChE, NO and MDA. Pretreatment with L. gerberiformis aqueous extract leaves protects against the combined effects of ovariectomy and CUMS-induced memory deficits, suggesting its anti-amnesic properties. These properties could be mediated through the prevention of estrogen decline, modulation of the cholinergic system and oxidative stress.

Role of Myokine Decorin and Cholecalciferol as Therapeutic Targets in Polycystic Ovary Syndrome induced by estradiol valerate in a rat model.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age. Oxidative stress (OS) has been documented to be one of the factors involved in the pathogenesis of PCOS. This research work was designed to assess the impact of Rosa damascena (RD) extract on protective components of OS and the levels of reactive oxygen species (ROS) and cyclooxygenase 2 (Cox2) as OS contributors in a rat model of estradiol valerate (EV)-induced PCOS. Adult female Wistar rats (n = 48) were divided into a control group (n = 12) and a PCOS group (n = 36), with PCOS induced by EV (4 mg/kg/day). To confirm PCOS induction, 6 rats from each group underwent estrous cycle evaluation and ovarian histology. The remaining rats—6 from the control group and 30 from the PCOS group—were assigned to five subgroups: a PCOS model group, a metformin-treated group (200 mg/kg/day), and three groups receiving RD extract at doses of 400, 800, or 1200 mg/kg/day for 28 days. OS parameters and Cox2 gene expression were assessed. OS parameters and the expression of the Cox2 gene were assessed. There were significant increases in OS parameters and decreases in ROS levels in the group with higher doses of RD extract (800 and 1200 mg/kg/day) and metformin compared to the PCOS group. Moreover, there was a significant decrease in Cox2 gene expression levels (P < 0.001). The RD extract showed potential therapeutic effects in alleviating PCOS complications, which seems partly due to improving the dysregulation of OS parameters.

To explore the mechanism of action of Tiaogeng decoction (, TG) in alleviating oxidative stress damage in the hippocampus of a mouse model of cognitive impairment. Amyloid precursor protein/presenilin-1 (APP/PS1) transgenic female mice were randomly divided into model, estradiol valerate, low-, medium-, and high-dose TG groups, female C57 mice were used as the control group (n = 12/group). After 12 weeks of treatment, the behavior of mice was tested with the Morris water maze, and brain tissue samples were collected, and changes in hippocampal neurons were observed using electron microscopy. The deposition of beta-amyloid protein (Aβ) amyloid plaques in the hippocampus was determined by light microscopy. Aβ1-42 protein levels were detected through immunofluorescence. Oxidative stress indicators in the hippocampus were detected by enzyme linked immunosorbent assay. The expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), c-Jun N-terminal kinase (JNK), phospho-JNK (p-JNK), B-cell lymphoma-2 (Bcl-2), caspase-9, and cleaved caspase-9 were detected by Western blot. Hippocampal cell apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated nick end Labeling. TG improved the cognitive function of APP/PS1 mice, as judged by improvements in several indices from the Morris water maze test. TG increased Nrf2, superoxide dismutase, and heme oxygenase-1 protein expression and reduced malondialdelyde and reactive oxygen species expression. TG also inhibited the expression of JNK proteins, upregulated the expression of Bcl-2, and downregulated the expression of caspase-9, reducing cell apoptosis. TG decreased the percentage of the hippocampal cornu ammonis 1 area positive for Aβ1-42, reducing mitochondrial damage caused by oxidative stress and Aβ protein deposition. TG may improve memory ability while reducing oxidative stress and apoptosis. It also reduces Aβ protein deposition in the hippocampus, protecting the central nervous system and improving memory function. TG may reduce the risk of AD.

Platelet-rich plasma therapy enhances endometrial receptivity in thin endometrium patients undergoing frozen embryo transfer cycles: results from a prospective cohort observational study.

This study aimed to describe characteristics and treatment choices among AMABs (Assigned Male At Birth) and AFABs (Assigned Female At Birth) transgenders enrolled from March 2021 to July 2023 at the PTA S. Giorgio of the ASP3-Catania. A total of 145 patients were studied, and there was no prevalence of AMAB/AFAB. At first observation for AMABs, the age was 26 years and 25 years for AFABs, with 11 AMAB/AFAB declared as "non-binary" (average age 17 years). In AMAB/AFAB, we evaluated hormonal treatment, efficacy, and dosage/hormonal levels. In AMABs, oral estradiol valerate (4 mg/day) or transdermal estradiol in gel (2 mg/day) + oral cyproterone acetate (25 mg/day) for both estrogenic formulations were used. Testosterone (TE), LH, FSH, and PRL at baseline and during chronic treatment were measured. In AFABs, we used injectable TE (250 mg/3-4 weeks or 1 g/12-16 weeks) or transdermal TE (60- 80 mg/day). In these patients, we analyzed blood count, LH, FSH, and TE. Hematocrit, hemoglobin, and red blood cell count showed a modest elevation after 4-6 months of treatment. About 32% of AFABs complained of transient uterine bleeding, but no hypertension or ovarian pathology was detected. In AMABs, despite the short observation period, no patient showed an increased risk of myocardial infarction and ischemic stroke. Among AFABs, no increased risk of cardiovascular or cerebrovascular disease was observed. Furthermore, given the complexity of the phenomenon, the integration between the different professional figures who require specific and qualified skills is fundamental.</p>.

BackgroundClinically, it has been observed that vaginal administration of the same dose of Micronized 17-beta estradiol hemihydrate (the Estradiol tablets of Femoston) significantly increases serum estradiol levels compared to oral administration. However, the clinical outcomes associated with this route of administration remain unclear. Additionally, the concentration of estradiol in endometrial tissue following vaginal administration of Micronized 17-beta estradiol hemihydrate (M17EH), as well as its potential impact on endometrial receptivity, has been poorly investigated.ObjectiveTo explore the relationship between different drug regimens of M17EH hormone replacement (HRT) and serum estradiol level, endometrial thickness and embryo implantation outcome in patients with thin endometrium during the frozen-thawed embryo transfer (FET) cycle, and to analyze the estradiol concentration in endometrial tissue of oral and vaginal administration of M17EH and its influence on endometrial receptivity.MethodA retrospective analysis was conducted on patients with thin endometrium. Subjects were divided into three groups based on different estrogen formulations and administration routes: Group A [oral Estradiol Valerate Tablets (Progynova)], Group B (oral M17EH), and Group C (oral combined with vaginal M17EH). Endometrial thickness, and clinical outcomes were compared across the three groups. For Groups B and C, endometrial tissue samples were collected five days after progesterone conversion. Estradiol concentration in tissues was detected and the endometrial receptivity markers [leukemia inhibitory factor, (LIF) and Mucins, (Muc1)] were evaluated.ResultsSerum estradiol levels and endometrial thickness in Group C were significantly higher than those in the other two groups (P < 0.05). While there were no statistically significant differences in abortion rate, and live birth rate among the three groups, the live birth rate was highest in Group C. Estradiol concentration in the endometrium was significantly higher following vaginal administration of M17EH compared to oral administration (P<0.05). No significant differences were observed in the expression of endometrial receptivity markers (LIF and MUC1) between oral and vaginal administration groups.ConclusionIn FET cycles, a HRT regimen combining oral and vaginal administration of Micronized 17-beta estradiol hemihydrate is more conducive to endometrial growth. Although vaginal administration results in higher estrogen levels, it does not appear to compromise endometrial receptivity.

Aim: Menopausal women are suffering from stress-related disorders, and in the previous studies, Khaya anthotheca (K. anthotheca) decoction exhibited estrogenic and anxiolytic properties. Taken together, the aim of this study was to evaluate the effects of K. anthotheca decoction on behavioral disorders and oxidative stress induced by repeated variable stress in ovariectomized Wistar rats. Methods: Forty-two female Wistar rats (10–12 weeks old; 145 ± 10 g) were used. They were ovariectomized (except those from the sham operated group). Fourteen days after ovariectomy, animals were randomly distributed into 7 groups (n = 6): sham operated and negative control groups receiving distilled water; two positive control groups receiving estradiol valerate and diazepam (1 mg/kg each), and three other groups receiving the tested doses of K. anthotheca extract (125, 250, and 500 mg/kg each). The treatment was applied every week. Anxiety, depression, and motor coordination were assessed throughout the experimental procedure. The anti-oxidative potential of the extract was evaluated in rat brain homogenate. Results: It was noted that K. anthotheca extract induced anxiolytic effects marked by an increase in the locomotory activity during open field, light/dark, and elevated plus maze tests. Besides, its anti-depressive effects were shown by a significant (p &lt; 0.05) decrease in the immobilization time during the forced swimming test. By improving the suspension time during grid and wire grip tests, the distance covered, and the number of switch directions during the beam walking test, the extract increased motor coordination. The antioxidant potential of the extract was marked by a significant decrease (p &lt; 0.01) in malondialdehyde level and an increase (p &lt; 0.05) in reduced glutathione level. Conclusions: These results provide valuable insights into the potential therapeutic application of the K. anthotheca extract; however, more studies are needed to elucidate mechanisms of action.

Comparative effectiveness of equol on estrogen and androgen disruption and metabolic parameters in adult male Sprague-Dawley rats.

Background Gender incongruence results from the mismatch between gender identity and thesex assigned at birth. The process of gender affirmation includes a series of procedures during which the transgender individual acquires phenotypic features of the desired sex. Hormonal therapy for transgender women aims to suppress endogenous androgens and replace them with estrogens. The present study sought to investigate the safety of feminizing therapy in transgender women in relation to somatometric and metabolic parameters. Methods The medical records of transgender women who received oral estradiol valerate and a gonadotropin-releasing hormone (GnRH) agonist for at least 18months were reviewed. The study population had estradiol levels within the normal limits of the follicular phase of cisgender women of reproductive age and suppressed blood testosterone levels after 18months of treatment. Changes in body mass index, glycemic and lipid profiles, hemoglobin and hematocrit, and liver function tests were examined. The paired t -test was used for statistical analysis. Results The mean blood estradiol and testosterone levels after approximately 18months of treatment were 85.65pg/mL and 24ng/dL, respectively. There was a statistically significant increase in blood triglycerides as well as a statistically significant decrease in hemoglobin and hematocrit. However, none of the participants developed severe hypertriglyceridemia or anemia. No significant changes were found in blood cholesterol (total, high-density lipoprotein, and low-density lipoprotein cholesterol), glucose, and liver enzymes. Conclusions Treatment with oral estradiol valerate and an intramuscular GnRH agonist is used in daily clinical practice to promote feminizing physical changes in transgender women. However, the possibility of side effects is not well documented. The present study demonstrated that achieving estradiol and testosterone levels within therapeutic targets is important for the safety of gender-affirming therapy.

Graphical abstractCurrent treatments for endometriosis are unsuitable for women who wish to conceive. To verify the supposed beneficial effects of Graptophyllum pictum (G. pictum) on reproductive diseases and inflammation, endometriosis was induced in female Wistar rats using a slightly modified protocol. After verification of successful transplantation (42 days), the animals were co-treated for 7 days with estradiol valerate (E2V; 0.5 mg/kg and the aqueous (GPC) or methanolic (GPM) extracts of G. pictum at doses of 50 and 275 mg/kg. Positive controls received aspirin (3 mg/kg) or letrozole (10 mg/kg). Normal and negative controls received vehicle (distilled water, 10 mL/kg). On day 7, animals were injected with oxytocin 30 min before sacrifice to evaluate some dysmenorrhea-like model parameters. Five animals per group were then sacrificed, and the remaining five animals were mated with males of proven fertility for 25 days. G. pictum extracts at all doses significantly (P < 0.001) increased the time of writhing latency and decreased its frequency and the volume of implant (P < 0.05) at the GPM 50 mg/kg dose. Levels of interleukin-6, tumor necrosis factor-alpha, and vascular angiogenic growth factor were reduced (P < 0.001) with all treatments. They also increased (P < 0.05) the serum superoxide dismutase and glutathione levels and decreased serum nitrite and malondialdehyde levels. In addition, the number of Graafian follicles (P < 0.05), fertility, and pregnancy rates were increased with the treatments. G. pictum extracts showed anti-inflammatory, antioxidant, and fertilizing effects in Wistar rats with endometriosis.Lay summaryAsymptomatic in some individuals, endometriosis is an estrogen-dependent disease that causes infertility and severe pelvic pain, especially during menstrual periods and sexual intercourse. Higher cesarean rates worldwide have led to more cases of endometriosis (scar endometriosis). The delay of diagnosis (between 2 and 13 years) leads to increased misdiagnosis among patients and healthcare costs. There is no cure, but current treatments aim to alleviate spasms and pain by inhibiting estrogen production, and they are therefore unsuitable for women wishing to conceive, since they affect ovulation. Hence, there is a need to seek medical treatments that do not prevent pregnancy. Apart from its ornamental worth, Graptophyllum pictum, also called caricature plant, is traditionally used to relieve pain and treat reproductive disorders. After abdominal auto-transplantation of uterine fragments in rats, water-based and alcohol-based extracts of G. pictum promoted fertility by improving menstrual pain, egg development, and reducing cell damage and inflammation, which contribute to the progression of endometriosis.

Background Frozen-thawed embryo transfer (FET) during the endometrial receptivity window is important for implantation.Objective This study aims to compare the clinical pregnancy rate in 2 methods of endometrial preparation in FET using the hormone replacement cycle (HRC) and the modified natural cycle (mNC).Materials and Methods In this randomized clinical trial, 128 infertile women who visited the Imam Khomeini hospital infertility clinic, Sari, Iran between April and October 2024 were randomly assigned to 2 groups (n = 64/each): the mNC frozen embryo transfer group and the HRC group. In the mNC frozen embryo transfer group, ovulation was induced using human chorionic gonadotropin, and the timing of frozen embryo transfer was scheduled based on ovulation. The HRC group received estradiol valerate until the endometrial thickness reached 8 mm, then daily injections of progesterone were added and FET were performed.ResultsThe participants had no significant differences in demographic characteristics. The primary outcome was clinical pregnancy rate with no significant difference between two groups(p = 0.282). No significant differences were observed between the mNC and HRC groups regarding the secondary outcome, which included human chorionic gonadotropin positive rate, chemical pregnancy rate, implantation rate, ongoing pregnancy rate, early miscarriage, ectopic pregnancy, twin pregnancy, and cycle cancellation rate. Significant differences were observed in the number of monitoring visits between the mNC frozen embryo transfer and HRC groups (p = 0.001).ConclusionAlthough the results indicate that the impact of both methods is similar, the fact that fewer visits are required in a natural cycle and there is also less need for hormones could make it preferable.

A 40-year-old transgender patient (assigned male at birth, pronouns: they/them) with paroxysmal atrial fibrillation presented for elective transoral chondrolaryngoplasty. They had been on gender-affirming hormone therapy with intramuscular estradiol valerate and oral progesterone for 16months and their atrial fibrillation was managed with flecainide and aspirin. The otolaryngology team recommended holding estrogen postoperatively to reduce venous thromboembolism (VTE) risk, but the patient expressed concern about withdrawal-related gender dysphoria and vasomotor symptoms. Transfeminine patients on estrogen are at higher risk of VTE compared to the general population Goodman M, Zhang Q. Stroke and Blood Clot Risk in Transgender Women Taking Hormones. Patient-Centered Outcomes Research Institute (PCORI); 202 Accessed November 18, 2024. http://www.ncbi.nlm.nih.gov/books/NBK593552/ . There has historically been concern about perioperative VTE in these patients in the context of gender affirming vaginoplasty, which is considered to have risk factors associated with VTE (lengthy pelvic surgery with prolonged bedrest) Coleman et al. in Int J Transgender Health. 23:S1-S259, 2022. Previously, it was routine practice to hold gender affirming estrogen perioperatively for vaginoplasty. However, newer literature has shown no increased risk with estrogen maintenance during vaginoplasty Coon et al. in Plast Reconstr Surg Glob Open. 11:e5033, 2023;Lee and Spiegel in The Laryngoscope. 132:918-919, 2022;, with the World Professional Association for Transgender Health (WPATH) guidelines now recommending the continuation of estrogen perioperatively Kozato et al. in J Clin Endocrinol Metab. 106:e1586-e1590, 2021 to avoid symptoms of estrogen withdrawal including gender dysphoria with increased risk of suicide, and vasomotor symptoms. Unfortunately, the practice of holding estrogen therapy perioperatively persists, and has been applied to many surgeries outside of vaginoplasty, even those with little VTE risk, such as this patient's facial feminization surgery Badreddine et al. in Eur Rev Med Pharmacol Sci. 26:2511-2517, 2022. Despite evidence and WPATH guidelines, discontinuation of estrogen therapy perioperatively remains common Lee and Spiegel in The Laryngoscope. 132:918-919, 2022. For this patient, the low bleeding and VTE risk allowed for a tailored approach. After discussing risks, the team opted for 2-week VTE chemoprophylaxis with Enoxaparin 40mg daily. The patient recovered well without bleeding or thromboembolic events. This case underscores the need to update surgical practices based on current evidence and prioritize patient-centered care.

Primary dysmenorrhea (PD) is characterized by lower abdominal spasms and painful cramps during menstruation in females with a normal pelvic anatomy. Cymbopogon citratus (DC.) Stapf, commonly known as lemongrass, is consumed in the form of herbal tea around the world. It has been traditionally used for menstrual disorders in several communities. This study aims to evaluate the traditional use of C. citratus for its efficacy in alleviating the symptoms of PD. C. citratus extract (CcE) was chemically characterized using HPLC and GCMS, which indicated the presence of several phenolic compounds and long-chain fatty acids. The anti-inflammatory activity of CcE was assessed by COX-I, COX-II, and 5-LOX enzyme inhibition with IC50 values of 143.7, 91.7, and 61.5 µg/mL, respectively, and showed good total antioxidant capacity and free radical scavenging activity. PD was induced in female Wistar rats by administering estradiol valerate followed by oxytocin to induce PD symptoms. CcE efficacy was assessed at 30, 100, and 300 mg/kg concentrations and compared with ibuprofen. CcE 300 mg/kg reduced abdominal contortions and inflammation in the rat uterus. The inflammatory (COX-II, TNFα and IL-10) and oxidative stress (TAC, TOS, MDA and SOD) markers in uterine tissue homogenate were also improved. An in vivo analgesic assessment through hot-plate, tail-flick, and acetic acid-induced writhing assays showed good analgesic activity by CcE, while ex vivo experiments described tocolytic effects in rat uterine muscles. CcE alleviates PD by its antioxidant, anti-inflammatory, analgesic, and tocolytic effects.

Development and evaluation of a novel non-competitive MAGLUMI estradiol chemiluminescence immunoassay.

Efficacy of Shuangdan Yangxue capsule combined with estradiol valerate and dydrogesterone in early-onset ovarian insufficiency

Exploring therapeutic avenues – an experimental study investigating the effects of soy isoflavone and estradiol valerate on HbA1c, lipid profile, urogenital complaints, vaginal maturity index, and sexual function in menopausal women: a comparative analysis using MENQOL-Quality of Life Assessment