Vitamin D binding protein correlate with estrogen increase after administration of human chorionic gonadotropin but do not affect ovulation, embryo, or pregnancy outcomes.

Background: Vitamin D binding protein (DBP) might increase substantially after ovarian stimulation and hence could be associated with IVF/ICSI outcomes because it determines the fraction of free bioavailable 25(OH) vitamin D. In this study, we aim to determine whether DBP is associated with E2 level after ovarian stimulation and IVF/ICSI outcomes. Design: Post-hoc analysis of a prospective observational cohort. Setting: Single-center study. Participants: 2569 women receiving embryo transfer. Intervention: None. Main outcome measures: The main outcomes were oocyte and embryo quality as well as pregnancy outcomes. Results: DBP concentration correlates with E2 on hCG day (=day of inducing ovulation with hCG; correlation coefficient r = 0.118, P<0.001) and E2 x-fold change to baseline level (r = 0.108, P<0.001). DBP is also positively correlated with total 25(OH)D (r = 0.689, R2 = 0.475, P<0.001) and inversely with free 25(OH)D (r=-0.424, R2=0.179, P<0.001), meaning that E2-stimulated DBP synthesis results in a decrease of free 25(OH)D during ovarian stimulation. However, such alteration does not affect IVF/ICSI outcomes when considering confounding factors, such as the number and quality of oocytes nor embryo quality as well as pregnancy outcomes. Conclusion: DBP concentration correlates with the degree of E2 increase after ovarian stimulation. DBP is also positively correlated with total 25(OH)D and inversely with free 25(OH)D, suggesting that the proportion of free 25(OH)D decreases during ovarian stimulation caused by E2-stimulated DBP synthesis. However, such alteration does not affect clinical IVF/ICSI outcomes.

Effect of exogenous oestrogen treatment frequency on induction of artificial lactation in pseudopregnant sows.

In this study, we examined whether the frequency of exogenous oestrogen treatment affects the induction of artificial lactation and milk production. Furthermore, we analysed changes in milk components obtained from artificially lactating sows. Pseudopregnant induced by treatment with 30 mg of estradiol dipropionate (EDP) on Day 10 (Day 0 = the last day of estrus) were divided into three groups: those administered 5 mg of EDP once on Day 39 (n = 5), twice on Days 32 and 39 (n = 5) and three times on Days 25, 32 and 39 (n = 6). All animals were treated with prostaglandin F2α (PGF2α) on Day 46 for induced lactation. Artificial lactation was induced in 66.7%-80.0% of sows, and the EDP treatment frequency before PGF2α administration had no significant effect on either the induction rate of artificial lactation or the milk yield during the experimental period. The milk composition (levels of crude protein, crude fat, crude ash, lactose and immunoglobulin) did not differ among the groups. In conclusion, the number of EDP treatments prior to PGF2α administration had no effect on either the efficiency of artificial lactation induction or milk production.

A randomized clinical trial of transdermal (gel) versus oral estrogen for endometrial preparation in frozen embryo transfer cycle.

OBJECTIVE: The aim of this study was to compare endometrial thickness with the use of transdermal estrogen (gel) versus oral estrogen (pills) for endometrial preparation in the frozen embryo transfer cycle and serum estrogen concentrations during the preparation cycle, side effects, and chemical and clinical pregnancy rates. METHODS: This was a prospective, randomized controlled trial of women undergoing endometrial preparation for cryopreserved blastocyst transfer. A total of 88 women were randomized, of which 82 completed the study protocol. Of this group, 44 received 6 mg/day of estradiol valerate orally (pills group) and 38 received 4.5 mg/day of estradiol hemihydrate transdermally (gel group). Endometrial thickness was measured using transvaginal ultrasound between the 7 and 10th day of the cycle. Serum estradiol concentrations were measured on the day of initiating the cycle, on control transvaginal ultrasounds, and on the day of embryo transfer. Side effects were documented at each study visit. p<0.05 were adopted as statistically significant. The groups were compared using Student's t-test for continuous variables and chi-square or Fisher's exact test for categorical variables. RESULTS: There were no significant group differences (p>0.05) in endometrial thickness, biochemical and clinical pregnancy rates, miscarriage rate, blood estradiol concentrations, duration of estradiol administration, or cycle cancellation rates. CONCLUSION: Endometrial preparation with transdermal estrogen yielded similar reproductive outcomes to oral estrogen with fewer side effects.

Effect of estrogen exposure on pregnancy outcomes in artificial frozen-thawed embryo transfer cycles.

In contemporary times, the employment of vitrification freezing technology has led to the widespread adoption of frozen-thawed embryo transfer (FET) worldwide. Meanwhile, hormone replacement therapy (HRT) is a crucial protocol for priming the endometrium during FET cycles. Estrogen is required in HRT cycles for the induction of progesterone receptors and to promote endometrial thickness. However, there is no universal consensus on the treatment duration, dosage regimen, administration route, and target serum estrogen levels. Therefore, this study aimed to offer a comprehensive review of these topics. A shorter duration of estrogen exposure may elevate the risk of early miscarriage, while prolonged exposure to estrogen does not seem to confer advantages to general population and may be attempted in individuals with thin endometrium. Moreover, excessive estrogen levels on the day of progesterone administration may be associated with higher miscarriage rates and lower live birth rates (LBR). To offer more comprehensive guidance for clinical practice, extensive and prospective studies involving a large sample size are warranted to determine the optimal concentration and duration of estrogen exposure.

Preoperative topical estrogen application in the management of hypospadias: a systematic review.

Local estrogen therapy has been explored as an alternative to conventional testosterone therapy in children requiring urethroplasty for hypospadias. Our objective is to evaluate if preoperative estrogen stimulation reduces post-urethroplasty complications and enhances penile dimensions. A systematic search was conducted on various databases, selecting only randomized controlled trials (RCTs) that tested estrogen on hypospadias patients under 18 years. Articles underwent sorting following PRISMA guidelines and bias risk was assessed using the JBI clinical appraisal tool for RCTs. Out of 607 screened records, 10 underwent full-text review, and 4 randomized controlled trials (RCTs) were selected for analysis. The total patient cohort across studies was 387 with 174 in the estrogen group. All studies utilized topical estrogen, but in different formulations and timings. Prudence is necessary for interpreting results due to variations in formulation, timing, and hypospadias type across studies. Limited by a small number of studies and outcome presentation non-uniformity, the review suggests no change in penile dimensions or postoperative complications with topical estrogen. Further research is needed to explore wound-healing properties of estrogen in hypospadias through animal and human studies.Registration and protocol: Registered in Prospero CRD42024502183.

Long-term therapy with dienogest or other oral cyclic estrogen-progestogen can reduce the need for ovarian endometrioma surgery.

BACKGROUND: Almost 10% of women in reproductive age are diagnosed with ovarian endometriomas and can experience symptoms and infertility disorders. Ovarian endometriomas can be treated with medical or surgical therapy. OBJECTIVE: To assess whether long-term therapy with dienogest or oral cyclic estrogen-progestogens is effective in reducing the size of ovarian endometriomas, alleviating associated symptoms, and reducing the requirement for surgery. DESIGN: Prospective non-interventional cohort study. METHODS: We enrolled childbearing women diagnosed with ovarian endometriomas. We collected demographic, clinical, and surgical data, including the evaluation of ovarian endometrioma-associated symptoms and pain using the visual analog scale. We grouped the women according to treatment regimen into dienogest, estrogen-progestogens, and no-treatment. Patient's assessment was performed at baseline and after 12 months evaluating the largest ovarian endometrioma diameter (in millimeters) and the associated symptoms. Furthermore, we analyzed the impact of hormonal treatment in a sub-group of women fulfilling at baseline the criteria for a first-line surgical approach (ovarian endometrioma > 30 mm with visual analog scale > 8 or ovarian endometrioma > 40 mm before assisted reproductive treatments or any ovarian endometrioma(s) > 60 mm). RESULTS: We enrolled 142 patients: 62, 38, and 42 in dienogest, estrogen-progestogens, and no-treatment groups, respectively. No significant differences were found regarding baseline characteristics. After 12 months, the mean largest ovarian endometrioma diameter increased in the no-treatment group (31.1 versus 33.8; p < 0.01), while a significant reduction was registered in the dienogest (35.1 versus 25.8; p < 0.01) and estrogen-progestogens (28.4 versus 16.7; p < 0.01) groups; no significant difference in ovarian endometrioma diameter reduction between these two latter groups was noted (p = 0.18). Ovarian endometrioma-associated symptoms and pain improved in dienogest and estrogen-progestogens groups, with a significantly greater effect for dienogest than for estrogen-progestogens for dysmenorrhea (74% versus 59%; p < 0.01). In the sub-group of women eligible for first-line surgery at baseline, long-term treatment with dienogest and estrogen-progestogens reduced surgical eligibility by 30%. CONCLUSIONS: Decreased mean largest ovarian endometriomas'diameter after 12 months and reduction of the need for surgical treatment by 30% were observed in dienogest and estrogen-progestogens groups. Long-term treatment with dienogest had a greater effect in alleviating dysmenorrhea and pain.

Use of menopausal hormone therapy beyond age 65 years and its effects on women's health outcomes by types, routes, and doses.

OBJECTIVES: The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths. METHODS: Using prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and Cox regression analyses adjusted for time-varying characteristics of the women, we examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular diseases, and dementia. RESULTS: Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%). For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer by 10%-19%, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer (45% or adjusted hazards ratio, 0.55; 95% CI, 0.50-0.60), ovarian cancer (21%), ischemic heart disease (5%), CHF (5%), and venous thromboembolism (5%), whereas E+ progesterone exhibited risk reduction only in CHF (4%). CONCLUSIONS: Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen.

Effect of hormone therapy on blood pressure and hypertension in postmenopausal women: a systematic review and meta-analysis.

IMPORTANCE: Menopausal hormone therapy (HT) includes a wide variety of hormonal compounds, and its effect on blood pressure is still uncertain. OBJECTIVE: The aim of this study was to assess evidence regarding the effect of HT on blood pressure in postmenopausal women and its association with arterial hypertension. EVIDENCE REVIEW: This systematic review and meta-analysis included randomized clinical trials and prospective observational studies. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and the incidence of hypertension were assessed. All stages were independently performed by two reviewers. For blood pressure outcome, standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated as effect measures. Heterogeneity was assessed using the I2 statistic. The results are presented based on the HT type. The incidence of hypertension was compared using descriptive analyses. FINDINGS: Eleven studies were included with 81,041 women evaluated, of which 29,812 used HT. The meta-analysis, conducted with 8 studies and 1,718 women, showed an increase in SBP with the use of oral conjugated equine estrogens plus progestogen (SMD = 0.60 mm Hg, 95% CI = 0.19 to 1.01). However, oral or transdermal use of estradiol plus progestogen (SMD = -2.00 mm Hg, 95% CI = -7.26 to 3.27), estradiol alone, and tibolone did not show any significant effect. No significant effect on DBP was observed for any formulation. Women who used oral estrogen plus progestogen had a higher risk of incident hypertension than those who never used it. CONCLUSIONS AND RELEVANCE: The effect of HT on blood pressure is influenced by the formulation used, especially the type of estrogen. The combined formulations of conjugated equine estrogens plus progestogen increased SBP and the risk of hypertension, which was not observed among estradiol plus progestogen, estradiol alone, and tibolone users.

Exogenous Estrogen in the Development of Head and Neck Cancer.

Importance: Sex differences in head and neck cancer (HNC) incidence suggest a potential contribution of sex hormones. Objective: To assess the role of exogenous estrogen exposure in the development of HNC in female patients. Design, Settings, and Participants: This large multicenter cohort study using clinical records from the TriNetX real-world database included 20 years of data (through May 31, 2023) from 87 health care organizations. The TriNetX database was searched for medical records for female patients with and without exogenous estrogen exposure according to their chronological age. Cohort 1 included 731 366 female patients aged 18 to 45 years old with regular oral contraceptive (OC) intake and cohort 2 included 3 886 568 patients in the same age group who did not use OC. Cohort 3 comprised 135 875 female patients at least 50 years old receiving hormone replacement therapy (HRT), whereas cohort 4 included 5 875 270 patients at least 50 years old without HRT. Propensity score matching was performed for the confounders age, alcohol dependence, and nicotine dependence. Data analyses were performed in May 2023. Main Outcome and Measures: Diagnosis of HNC (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision: C00-C14), and after propensity score matching (1:1 nearest-neighbor greedy matching), a risk analysis to investigate risk differences and risk ratios (RRs) with a 95% CI. Results: Among the 718 101 female patients in each of cohorts 1 and 2 (mean [SD] age at diagnosis, 25.9 [6.7] years), those with OC intake had a higher risk of an HNC diagnosis (RR, 1.47; 95% CI, 1.21-1.78) than those without OC use. Among the 131 835 female patients in each of cohorts 3 and 4 (mean [SD] age, 67.9 [12.0] years), those with postmenopausal HRT intake had a lower risk of an HNC diagnosis (RR, 0.77; 95% CI, 0.64-0.92) than those without HRT use. Conclusions and Relevance: The findings of this cohort study illustrate a positive association between OC and a negative association between HRT and the development of HNC in female patients. Given the limitations of the TriNetX database, future research should include detailed information on the intake of OC and HRT and reproductive health information (eg, age at menarche/menopause, number of pregnancies) to more accurately define the strength and direction of the possible association between exogeneous estrogen exposure and the development of HNC in female patients.

Prediagnostic use of menopausal hormone therapy and long-term survival of localized epithelial ovarian cancer: The Extreme study.

Use of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long-term MHT use, especially estrogen therapy (ET), was associated with improved long-term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long-term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000-2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo-values, 5- and 10-year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5-year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10-year survival. Use of MHT was not significantly associated with an improved 5- or 10-year survival in women with localized EOC (5-year relative survival probability = 0.95, 95% CI: 0.89-1.02; 10-year relative survival probability = 0.92, 95% CI: 0.84-1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long-term survival of localized EOC.

Assistência ginecológica aos transgênero / Gynecological care for transgenders

Transgênero (trans) é um termo que alberga toda a diversidade de gênero. A incongruência de gênero faz parte desse espectro e refere-se à pessoa cuja identidade de gênero é oposta ao sexo que lhe foi atribuído no nascimento. A terapia hormonal de afirmação de gênero, bem como a cirurgia de afirmação de gênero, é necessária para adequar o corpo ao gênero ao qual a pessoa se identifica. Os homens trans necessitam da terapia com testosterona, que visa reduzir as concentrações de estradiol e incrementar a testosterona circulante para níveis fisiológicos masculinos, resultando em masculinização. A mulher trans receberá o estradiol, associado ou não a um antiandrogênico, visando reduzir a testosterona e incrementar o estrogênio para níveis femininos, resultando em feminização. A cirurgia de afirmação de gênero é, frequentemente, requerida para completar as modificações fenotípicas para o homem e a mulher trans. O ginecologista e obstetra tem um papel crucial no provimento de cuidados a essa população. O presente artigo visa sistematizar algumas ações que o ginecologista e obstetra pode oferecer e que têm potencial para melhorar a qualidade de vida dos homens e mulheres trans. (AU)

Transgenero (trans) is an umbrella term that encompasses all gender diversity. Gender Incongruity is part of this spectrum and refers to the person whose gender identity is opposed to the sex assigned to them at birth. Gender-affirming hormone therapy as well as gender-affirming surgery are necessary to adapt the body to the gender to which the person identifies. Trans men require testosterone therapy to reduce estradiol concentrations and increase circulating testosterone to male physiological levels resulting in masculinization. Trans women will receive estradiol associated or not with an antiandrogenic to reduce testosterone and increase estrogen to female levels resulting in feminization. gender-affirming surgery is often required to complete phenotypic modifications for trans men and women. The gynecologist and obstetrician plays a crucial role in to provide care to this population. This article aims to systematize some actions that the gynecologist and obstetrician can offer to improve the quality of life of trans men and women. (AU)

Risk of breast cancer with HRT depends on therapy type and duration.

The studyVinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases. BMJ 2020;371:m3873. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/risk-of-breast-cancer-with-hrt-depends-therapy-type-and-duration/.

Comparative effects of estrogen and silibinin on cardiovascular risk biomarkers in ovariectomized rats.

BACKGROUND: Silibinin is a polyphenolic compound that could modulate estrogen receptor activation. Vascular dysfunction is considered a key initiator in atherosclerosis and may occur in the postmenopausal period. This manuscript compares estrogen and silibinin's impacts on factors that change endothelial function in ovariectomized (OVX) rats. METHODS: 32 female Wistar rats were subdivided into control; OVX; OVX + estrogen (1 mg/kg/day); and OVX + silibinin (50 mg/kg/day) groups. After the experimental period, lipid profile, atherogenic indices, and histopathology of endothelium were monitored. The vascular oxidative stress, adhesion molecules, inflammatory cytokine levels, nitric oxide (NO), angiotensin-II (Ang-II), and endothelin-1 (ET-1) were also analyzed. RESULTS: Silibinin treatment, similar to estrogen, significantly normalized the adverse changes of OVX on vascular function, including improved lipid profile and oxidative stress, increased endothelial nitric oxide synthase (eNOS) expression, diminished inflammatory status, and reduced adhesion molecule levels, ET-1 and Ang-II substances. Our findings also revealed that the administration with estrogen or silibinin resulted in a normal endothelium layer in the aorta tissues of OVX rats. CONCLUSION: Estrogen and silibinin have similar effects in improving vascular function. These treatments' protective impacts on vasculature indicate their potential benefits on the cardiovascular system in the postmenopausal period.

The Influence of Intravaginal Gestagens Treatment on the Morphological Features and Endometrial Steroid Hormone Receptors Content during Anestrus Type II in Dairy Cattle.

BACKGROUND: Gestagens are the most widely used therapy in anestrus type II. The aim of this research is to evaluate the effectiveness of the vaginal progesterone inserts therapy in anestrus type II in cows. METHODS: The study was conducted on 33 cows. Progesterone (PR) and estrogen (ER) receptors expression in endometrium was assessed on a molecular level based on mRNA tissue expression. Additionally, blood 17ß-estradiol and progesterone levels were evaluated. RESULTS: A decrease in mRNA expression of A and B PR and ER α was noted in treated and untreated animals. In the treated group, an increase of ERß mRNA expression was observed, while a decreased was found in untreated animals. There was increased PR, ERα and ß expression in endometrial tissue in treated cows, and decreased expression of these factors in untreated cows. In the treated group, recurrence of ovarian cyclicity was noted in 52% of animals and pregnancy was obtained in 34.8% of them, while in the untreated group, recurrence did not occur. In the control group, spontaneous recurrence of ovarian cyclicity was not observed. An increase of PR expression was correlated with increased proliferation of endometrial cells. CONCLUSIONS: It seems likely that the endometrium is well developed and ready for placentation after removing the exogenous source of progesterone and preventing the recurrence of cyclicity of ovaries.

Distinct and Convergent Beneficial Effects of Estrogen and Insulin on Cognitive Function in Healthy Young Men.

CONTEXT: Systematic investigations into the cognitive impact of estradiol and insulin in male individuals are sparse, and it is unclear whether the 2 hormones interact to benefit specific cognitive functions in humans. OBJECTIVE: We investigated the acute effect of estradiol and insulin and of their combined administration on divergent (creative) and convergent (arithmetical) thinking as well as short-term and working verbal memory in healthy young men. METHODS: According to a 2 × 2 design, 2 groups of men (each n = 16) received a 3-day transdermal estradiol (100 µg/24 h) or placebo pretreatment and on 2 separate mornings were intranasally administered 160 IU regular human insulin and, respectively, placebo before completing a battery of cognitive tests; we also determined relevant blood parameters. RESULTS: Estrogen compared with placebo treatment induced a 3.5-fold increase in serum estradiol and suppressed serum testosterone concentrations by 70%. Estrogen in comparison to placebo improved creative performance, that is, verbal fluency and flexibility, but not arithmetical thinking, as well as verbal short-term memory, but not visuospatial memory. The combination of estrogen and insulin enhanced recognition discriminability at delayed verbal memory recall; insulin alone remained without effect. CONCLUSION: Estrogen specifically enhances core aspects of creativity and verbal memory in young male individuals; delayed recognition memory benefits from the combined administration of estradiol and insulin. Our results indicate that insulin's acute cognitive impact in young men is limited and not robustly potentiated by estradiol. Estradiol per se exerts a beneficial acute effect on creative and verbal performance in healthy young men.

Vaginal estrogen and association with dementia: A nationwide population-based study.

INTRODUCTION: Use of systemic hormone therapy has been positively associated with development of dementia. Little is known about the dose-dependent effect of vaginal estradiol on dementia risk. METHODS: We assessed associations between cumulative dose of vaginal estradiol tablets and dementia in a case-control study nested in a nationwide Danish cohort of women aged 50 to 60 years at study initiation, who did not use systemic hormone therapy. Each case was age-matched to 10 female controls. RESULTS: A total of 4574 dementia cases were matched to 45,740 controls. Cumulative use of vaginal estradiol tablets was not associated with all-cause dementia; adjusted hazard ratio 1.02 (95% confidence interval [CI] 0.89-1.18) for low dose (< 750 mcg), 1.07 (0.94-1.21) for medium dose (750-2000 mcg), and 0.93 (0.84-1.03) for high dose (> 2000 mcg). Similarly, Alzheimer's disease (AD) only was not associated with vaginal estradiol. DISCUSSION: Exposure to vaginal estradiol tablets was not associated with all-cause dementia or AD only.

Influence of Age and Estradiol on Sympathetic Nerve Activity Responses to Exercise in Women.

INTRODUCTION: Postmenopausal women (PMW) display exaggerated increases in blood pressure (BP) during exercise, yet the mechanism(s) involved remain unclear. Moreover, research on the impact of menopausal changes in estradiol on cardiovascular control during exercise are limited. Herein, we tested the hypothesis that sympathetic responses during exercise are augmented in PMWcompared with young women (YW), and estradiol administration attenuates these responses. METHODS: Muscle sympathetic nerve activity (MSNA) and mean arterial pressure (MAP) were measured in 13 PMW (58 ± 1 yr) and 17 YW (22 ± 1 yr) during 2 min of isometric handgrip. Separately, MSNA and BP responses were measured during isometric handgrip in six PMW (53 ± 1 yr) before and after 1 month of transdermal estradiol (100 µg·d-1). A period of postexercise ischemia (PEI) to isolate muscle metaboreflex activation followed all handgrip bouts. RESULTS: Resting MAP was similar between PMW and YW, whereas MSNA was greater in PMW (23 ± 3 vs 8 ± 1 bursts per minute; P < 0.05). During handgrip, the increases in MSNA (PMW Δ16 ± 2 vs YW Δ6 ± 1 bursts per minute; P < 0.05) and MAP (PMW Δ18 ± 2 vs YW Δ12 ± 2 mm Hg; P < 0.05) were greater in PMW and remained augmented during PEI. Estradiol administration decreased resting MAP but not MSNA in PMW. Moreover, MSNA (PMW (-E2) Δ27 ± 8 bursts per minute versus PMW (+E2) Δ12 ± 5 bursts per minute; P < 0.05) and MAP (Δ31 ± 8 mm Hg vs Δ20 ± 6 mm Hg; P < 0.05) responses during handgrip were attenuated in PMW after estradiol administration. Likewise, MAP responses during PEI were lower after estradiol. CONCLUSIONS: These data suggest that PMW exhibit an exaggerated MSNA and BP response to isometric exercise, due in part to heightened metaboreflex activation. Furthermore, estradiol administration attenuated BP and MSNA responses to exercise in PMW.

Possible involvement of female sex steroid hormones in intracellular signal transduction mediated by cytokines following traumatic brain injury.

INTRODUCTION: The aim of this study was to determine the anti-inflammatory effect of female sex hormones on the level of intracellular molecules of cytokine signaling pathway after diffuse traumatic brain injury (TBI) in ovariectomized rats. METHODS: Female rats were divided into 10 groups: control, sham, TBI, Vehicle (oil), Vehicle E1 (33.3 µg/kg), E2 (1 mg / kg), P1 (1.7 mg/kg), P2 (8 mg / kg), E2 + P1. All drugs were injected 0.5 h after TBI. Brain edema and the brain levels of P-STAT-3, NFκB-P52, NFκB-P65, P-IκB, and SOCS-3 by immunohistochemistry measured at 24 h after TBI. RESULTS: Increased brain edema after TBI was inhibited by different doses of estrogen, progesterone (P < 0.001), and E2 + P1 (P < 0.05). The brain levels of P-STAT-3, NFκB-P52, NFκB-P65, and p-IκBα that increased after TBI was decreased only by E2 (P < 0.05). E2 and E2 + P1 have increased the SOCS-3 level after TBI (P < 0.05). Also, there was a difference between the E2 with E1 and two progesterone doses (P < 0.05). So that in all cases, the effects of E2 were more significant than the other groups. The target cells for these effects of E2 were microglia and astrocytes. CONCLUSION: The results indicate that one of the probable mechanism(s) of estrogen anti-inflammatory effect after TBI is either reduction of p-STAT-3, NFκB-P52, p-NFκB-P65, and p-IκBα or increase in SOCS-3 molecules involved in the signaling pathway of inflammatory cytokines.