Increased Serum E2 Levels Research Articles

Dynamic Evolution of Cardiac Function and Glucose and Lipid Metabolism in Ovariectomized Rats and the Intervention Effect of Erxian Decoction.

Abnormal changes in cardiac function have been reported in menopausal women, but there are few clinical studies on this topic. Erxian decoction (EXD) is a classic prescription that is widely used in the treatment of female menopausal diseases. The purpose of this study was to investigate the dynamic evolution of cardiac function and glucose and lipid metabolism in ovariectomized (OVX) rats and the intervention effect of EXD. The OVX climacteric rat model was established by bilateral ovariectomy. After successful modeling, the rats were randomly divided into four groups: the sham operation (SHAM) group (equal volumes of purified water), OVX group (equal volumes of purified water), estradiol (E2) group (1.8 × 10-4 g/kg), and EXD group (9 g/kg). Each group of rats was treated for 16 weeks. At the 4th, 8th, 12th, and 16th weeks after treatment, the cardiac function of the rats in each group was evaluated by ultrasound. The coaxial method was used to measure blood pressure (BP). Serum endothelin-1 (ET-1) and angiotensin-2 (Ang II) levels were determined by the enzyme-linked immunosorbent assay (ELISA). The strip method was used to measure fasting blood glucose (FBG). The serum total cholesterol (TC) and triglyceride (TG) levels of rats were measured with the oxidase method. Direct methods were used to measure serum high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels. At week 16 of dosing, serum E2 levels were determined by E2 radioimmunoassay. The myocardium and uterus of the rats in each group were stained with HE (hematoxylin-eosin). The ultrastructure of the rat myocardium was observed by electron microscopy. After the 16th week of treatment, the serum E2 level decreased (P < 0.05), and the uterus was atrophied in OVX rats. The cardiac ejection fraction (EF%) decreased at 4 weeks after treatment, and systolic and diastolic function decreased after 12 weeks. After the 16th week, the EF%, which reflects the "pump" function of the heart, decreased significantly (P < 0.05 or P < 0.01). At the 4th, 8th, 12th, and 16th weeks of treatment, the systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean pressure (MBP) of the rats in the OVX group increased with time (P < 0.05 or P < 0.01). The serum ET-1 and Ang II levels of rats in the OVX group increased (P < 0.05 or P < 0.01). In the OVX group, FBG was increased (P < 0.05 or P < 0.01), and blood lipids, especially LDL-C, were significantly increased (P < 0.05 or P < 0.01). After the 16th week of treatment, the myocardial tissue of OVX rats showed obvious pathological changes. EXD significantly increased serum E2 levels (P < 0.01), decreased ET-1 and Ang II levels (P < 0.01), reduced the cardiac function risk factors BP, FBG, and blood lipids, and significantly improved cardiac function and structural changes in OVX rats (P < 0.05 or P < 0.01). EXD can improve abnormal cardiac structure and function in OVX rats.

Bisphenol A exposure advances puberty onset by changing Kiss1 expression firstly in arcuate nucleus at juvenile period in female rats

Bisphenol A (BPA) is ubiquitous in the environment and its adverse effects on precocious puberty have been reported. But its mechanism is not clear. In the present study, the potential effects of BPA on endocrine functions of hypothalamus, especially in the arcuate (ARC) nucleus and anteroventral periventricular (AVPe) nucleus, were studied from postnatal day 15 (PND15) to PND35 in female Sprague-Dawley (SD) rats. Neonatal rats were exposed to 0.5 mg·kg−1·day−1 BPA or corn oil vehicle from PND1 to PND14 via intramuscular injection. From PND20 to PND 25, BPA caused enrichment of H3K4me2 and H3K4me3 at Kiss1 promoter, concurrent with elevated gene expressions of Kiss1 and GnRH1 in ARC and strikingly increased serum E2 levels in BPA group on PND25. Until PND30, BPA induced obviously overexpression of Kiss1 and GnRH1 in AVPe nucleus. Subsequently, the vagina opening and first ovulation had occurred earlier in rats with BPA exposure in respect to vehicle by PND35. In this study, it is suggested that the effects of BPA on precocious puberty may be due to its action to activate Kiss1 gene in ARC during the juvenile period (from PND20 to PND25) firstly, subsequently to evoke the AVPe neurons, resulting in precocious puberty in the end.

Sexual Maturity Promotes Yolk Precursor Synthesis and Follicle Development in Hens via Liver-Blood-Ovary Signal Axis.

Simple SummaryThe current work evaluates the liver-blood-ovary signal axis in relation to age changes involved in regulating egg yolk precursor synthesis in chickens. In this study, we observe the morphology and histology of the liver and ovary and determine the serum biochemical parameters and the expression abundance of the critical genes from the age of 90 days (d90) to d153. The mRNA and protein expressions of estrogen receptor-alpha (ER-α) and E2 levels in the liver and serum, respectively, showed similar changes. Moreover, with reference to an increased serum E2 level, the mRNA expression of genes related to yolk precursor synthesis (very low density apolipoprotein-II (ApoVLDL-II) and vitellogenin-II (VTG-II)), lipogenesis (fatty acid synthase (FAS)), and lipid transport (microsomal triglyceride transport protein (MTTP)) in the liver showed up-regulation.Several reproductive hormones were reported to be involved in regulating egg yolk precursor synthesis in chickens; however, the mechanism that shows how the liver-blood-ovary signal axis works in relation to age changes has not been reported yet. Therefore, in this study, we observe the morphology and histology of the liver and ovary and determine the serum biochemical parameters and the expression abundance of the critical genes from d90 to 153. Results show that the body weight and liver weight were significantly increased from d132, while the ovary weight increased from d139. Aside from the increase in weight, other distinct changes such as the liver color and an increased deposition of large amounts of yolk precursors into the ovarian follicles were observed. On d139, we observed small fatty vacuoles in the hepatocytes. The results of serum biochemical parameters showed a significant increase in the estradiol (E2) level, first on d125, and then it reached its peak on d132. Meanwhile, the levels of follicle-stimulating hormone (FSH) increased initially and then remained at a high level from d146 to d153, while the levels of luteinizing hormone (LH) increased significantly on d132 and reached the top level on d153. Moreover, the levels of lecithin (LEC), vitellogenin (VTG), very low density lipoprotein y (VLDLy), triglyceride (TG), and total cholesterol (TC) were significantly increased at d125 and were close from d146 to d153. The mRNA and protein expression of estrogen receptor-alpha (ER-α) and E2 levels in the liver and serum, respectively, showed similar changes. Moreover, with reference to an increase in serum E2 level, the mRNA expression of genes related to yolk precursor synthesis (very low density apolipoprotein-II, ApoVLDL-II) and vitellogenin-II (VTG-II), lipogenesis (fatty acid synthase, FAS), and lipid transport (microsomal triglyceride transport protein, MTTP) in the liver showed up-regulation. These results suggest that the correlation between liver-blood-ovary alliances regulate the transport and exchange of synthetic substances to ensure synchronous development and functional coordination between the liver and ovary. We also found that E2 is an activator that is regulated by FSH, which induces histological and functional changes in the hepatocytes through the ER-α pathway.

Estradiol levels are elevated in older men with diffuse cutaneous SSc and are associated with decreased survival

BackgroundSystemic sclerosis (SSc) is a female-predominant disease, characterized by excessive extracellular matrix deposition (ECM) with dermal and internal organ fibrosis. Considering the sex-based disparity in disease incidence, estradiol (E2), an estrogen form with pro-fibrotic effects, may play a role in SSc. We reported that post-menopausal women with diffuse cutaneous (dc)SSc have higher serum E2 levels compared to similar aged, healthy controls. Since males with SSc tend to have more severe disease, we examined serum E2 in dcSSc males in relation to disease characteristics and survival.MethodsWe measured serum E2 in 83 dcSSc men > 50 years old from the University of Pittsburgh Scleroderma Center and similar aged healthy controls. Using statistical modeling, we examined the associations between serum E2, internal organ involvement, autoantibody profiles, and survival.ResultsMale dcSSc patients had significantly higher serum E2 levels compared to healthy males and similar aged dcSSc post-menopausal women. Male dcSSc patients with high serum E2 had significantly more heart involvement, a trend for higher skin thickness progression rate, and worse survival. Using Cox regression modeling, increased serum E2 levels in anti-Scl-70 antibody-positive dcSSc males were associated with an increased risk of death.ConclusionsdcSSc males > 50 years old have higher levels of serum E2 compared to healthy controls and dcSSc post-menopausal women. Elevated serum E2 levels in dcSSc males are associated with heart involvement, trend to progression of dermal fibrosis, and, if anti-Scl-70 antibody positive, worse survival. Our study expands on previous work implicating E2 in dermal fibrosis in SSc and associates E2 levels with internal organ involvement and survival. These data suggest a role for estrogen imbalance in dcSSc.

Modulating Effects of Progesterone on Spontaneous Nocturnal and Ghrelin-Induced GH Secretion in Postmenopausal Women.

Oral administration of estradiol (E2) generally increases GH secretion in postmenopausal women. Oral administration of E2 is associated with a decrease in IGF-1, whereas parenteral or transdermally administered E2 may have no effect on GH. The effect of progesterone (P4) on GH secretion has rarely been studied. We hypothesized that moderately increased serum E2 levels stimulate GH and that P4 modulates E2-stimulated GH secretion. Four parallel groups of randomly assigned postmenopausal women (n = 40). Treatments were saline placebo and oral placebo, saline placebo and oral micronized P4 (3 × 200 mg/d IM), E2 (5 mg IM) and oral placebo, and E2 IM and oral micronized P4. Outcome measures were overnight GH secretion (10 hours), stimulated (ghrelin, 0.3 µg/kg IV bolus) GH secretion, and CT-estimated visceral fat. Intramuscular E2 administration did not alter nocturnal and ghrelin-stimulated GH secretion. Nocturnal GH secretion was not changed by P4 administration. However, P4 diminished ghrelin-stimulated pulsatile GH release with or without E2 (average, 7.20 ± 2.14 and 9.58 ± 1.97 µg/L/2 h, respectively; P = 0.045). Respective outcomes for mean GH concentrations and GH peak amplitudes were 0.97 ± 0.31 and 1.52 μg/L ± 0.29 (P = 0.025) and 2.76 ± 1.04 and 3.95 μg/L ± 0.90 (P = 0.031). Ghrelin-stimulated GH secretion correlated negatively with P4 concentration with or without correction for visceral fat area in the regression equation (R = 0.49, P = 0.04, β = -0.040 ± 0.016). Low-range physiological E2 concentrations do not affect spontaneous or ghrelin-stimulated pulsatile GH secretion. Conversely, P4 inhibits ghrelin-stimulated GH secretion in a concentration-dependent fashion. The mechanistic aspects and physiological significance of natural P4's regulation of ghrelin-evoked GH secretion require further study.

Effect of Perinatal Blockade of Androgen Receptors on Estrogen Receptor‐Levels in Specific Brain Regions and Spatial Working Memory in Male Rats

Sex differentiation of the male rat brain occurs during the perinatal period (four days prior to and four days after birth) in the presence of testosterone (TS) which serves as a prehormone and gets metabolized to either 17β‐estradiol (E2) or dihydrotestosterone (DHT). E2 exerts its effect by binding to estrogen receptor (ER‐ and ER‐β) and DHT to androgen receptor (AR). Both ER and AR are shown to be important in the sexual differentiation of the brain. ER‐ is expressed in the hypothalamus, amygdala, and hippocampus in greater amounts and is associated with memory and sexual behavior. Whether blockade of AR during the perinatal period modulates the concentrations of ER‐ in the adult brain and, in turn, affects spatial working memory (SWM) was tested in this study. Two timed‐pregnant Long Evans rats were administered Flutamide (20mg/kg; SC) or vehicle during the last four days of pregnancy. Ten mg/kg (SC) of flutamide or vehicle was given to the newborn male pups for an additional four days. We tested SWM in these male rats when they reached postnatal day 65 and found that flutamide treatment improved SWM compared to control animals. At the end of the behavioral study, these animals were sacrificed and trunk blood was collected to measure serum E2 and TS levels. We found that the behavioral changes were associated with elevated serum E2 and reduced TS levels. The hypothalamus, amygdala, and hippocampus were isolated from the frozen brain tissue and ER‐ protein levels were measured using chemiluminescent western blots. Flutamide‐treated group showed an increase in ER‐ levels in the hypothalamus and the amygdala whereas concentrations in the hippocampus was decreased. Our results suggest that the increased ER‐ levels in the hypothalamus and amygdala along with increased serum E2 levels appear to improve SWM.

Impact of new systemic oral and local, hormonal and non-hormonal treatments on genitourinary syndrome and Vulvo-Vaginal-Atrophy (VVA) through the menopausal transition: the right therapy in patients at risk

During the menopausal transition, women experience a number of symptoms due to declining estrogen levels, including vasomotor symptoms and vulvar and vaginal atrophy (VVA). Unlike vasomotor symptoms, vaginal dryness and dyspareunia, the main symptoms of VVA, typically worsen without treatment and can significantly impact the quality of life. Up to 60% of postmenopausal women may be affected by VVA, but many women unfortunately do not seek treatment due to embarrassment, cardiovascular and oncologic risk factor, or other factors. Therefore, local estrogen treatment is still controversial due to the systemic absorption of estradiol and its potential effects on the breast and endometrium.The fact that up to 26% of women using systemic hormonal therapy continue to experience symptoms of urogenital atrophy is sufficient reason to justify not recommending systemic hormonal therapy in women with vaginal symptoms only; many women initially require a combination of systemic and local estrogen therapy, especially when it is used at low doses.Intravaginal application of DHEA as an alternative treatment compared to local estrogen therapy. Intravaginal DHEA does not increase serum E2 levels and may be a better option for long term treatment of VVA as there is no increase in serum E2 levels with DHEA. Previous data have shown that intravaginal dehydroepiandrosterone (DHEA, prasterone) improved all the domains of sexual function, an effect most likely related to the local formation of androgens from DHEA.As the first non-hormonal alternative to estrogen-based products for this indication, the approval of ospemifene represents a significant milestone in postmenopausal women's health. Ospemifene is a non-steroidal estrogen receptor agonist/antagonist, also known as a selective estrogen receptor modulator (SERM), which seems to be effective in genitourinary symptoms.There is now a new alternative to systemic hormone therapy with estrogen/gestagens. The tissue-selective estrogen complex (TSEC) which combines a SERM (bazedoxifene, BZA) with conjugated equine estrogens (CEE) is designed not only to improve menopausal symptoms but to prevent osteoporosis, while maintaining the benefits of estrogen therapy on vasomotor symptoms and vulvovaginal atrophy, but antagonizing stimulatory effects on the endometrium and mammary gland. The two studied doses of BZA/CEE (20 mg BZA + 0.425 mg CEE and 20 mg BZA + 0.625 mg CEE) have been shown to improve the percentage of superficial cells, reducing the percentage of basal cells. Thus, 20 mg BZA + 0.625 mg CEE reduces the severity of symptoms caused by atrophic vulvovaginitis by 56% and normalizes vaginal histology and pH. This efficacy persists for 2 years.Here we aim to evaluate current experimental and actual clinical strategies to achieve the main therapeutic goal for genitourinary syndrome and VVA in menopause which is the relief of symptoms, a better quality of life and women’ s health in menopausal women not eligible for Hormonal Replacement Therapy (HRT).

Effects of electroacupuncture on bone mass and cathepsin K expression in ovariectomised rats.

To characterise the effects of early and late electroacupuncture (EA) treatment on serum 17β-oestradiol (E2), C-terminal cross-linking telopeptide of type I collagen (CTX-I), bone mineral density (BMD), biomechanical bone strength and mRNA expression of cathepsin K in ovariectomised (OVX) rats. Sixty Sprague-Dawley rats underwent ovariectomy (n=40) or sham surgery (n=20) and were randomly divided into two batches. Batch 1 (n=30) consisted of 10 sham-operated rats (Sham-0 group) and 20 OVX rats: half commenced EA immediately (early EA group, n=10) and half were left untreated (OVX-0 group, n=10). Batch 2 (n=30) consisted of 10 sham-operated rats (Sham-12 group) and 20 OVX rats: half commenced EA treatment 12 weeks after ovariectomy (late EA group, n=10) and half were left untreated (OVX-12 group, n=10). Rats in batches 1 and 2 were killed after 12 and 24 weeks, respectively. Serum E2, CTX-I, BMD, bone strength and cathepsin K expression were determined by ELISA, dual energy X-ray absorptiometry, biomechanical assessment and qRT-PCR, respectively. Both early and late EA treatment increased serum E2 levels, reduced serum CTX- I levels and increased BMD and bone strength of the L5 vertebral body in OVX rats. Although early EA treatment similarly increased BMD and bone strength of the femur, late EA treatment did not. However, both early and late EA treatment reduced mRNA expression of cathepsin K in OVX rats. Early EA completely prevented and late EA partially prevented bone loss and deterioration of bone strength in OVX rats. The timing of initiation of EA treatment may be an important consideration for optimisation of effects. The influence of EA on bone strength appears to be at least partially mediated through regulation of the expression of cathepsin K.

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats.

Objective:To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol.Materials and Methods:Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay.Results:At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group.Conclusions:Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women.

Estradiol replacement enhances sleep deprivation-induced c-Fos immunoreactivity in forebrain arousal regions of ovariectomized rats

To understand how female sex hormones influence homeostatic mechanisms of sleep, we studied the effects of estradiol (E(2)) replacement on c-Fos immunoreactivity in sleep/wake-regulatory brain areas after sleep deprivation (SD) in ovariectomized rats. Adult rats were ovariectomized and implanted subcutaneously with capsules containing 17beta-E(2) (10.5 microg; to mimic diestrous E(2) levels) or oil. After 2 wk, animals with E(2) capsules received a single subcutaneous injection of 17beta-E(2) (10 microg/kg; to achieve proestrous E(2) levels) or oil; control animals with oil capsules received an oil injection. Twenty-four hours later, animals were either left undisturbed or sleep deprived by "gentle handling" for 6 h during the early light phase, and killed. E(2) treatment increased serum E(2) levels and uterus weights dose dependently, while attenuating body weight gain. Regardless of hormonal conditions, SD increased c-Fos immunoreactivity in all four arousal-promoting areas and four limbic and neuroendocrine nuclei studied, whereas it decreased c-Fos labeling in the sleep-promoting ventrolateral preoptic nucleus (VLPO). Low and high E(2) treatments enhanced the SD-induced c-Fos immunoreactivity in the laterodorsal subnucleus of the bed nucleus of stria terminalis and the tuberomammillary nucleus, and in orexin-containing hypothalamic neurons, with no effect on the basal forebrain and locus coeruleus. The high E(2) treatment decreased c-Fos labeling in the VLPO under nondeprived conditions. These results indicate that E(2) replacement modulates SD-induced or spontaneous c-Fos expression in sleep/wake-regulatory and limbic forebrain nuclei. These modulatory effects of E(2) replacement on neuronal activity may be, in part, responsible for E(2)'s influence on sleep/wake behavior.

A study of 17β-estradiol-regulated genes in the vagina of postmenopausal women with vaginal atrophy

Background Vaginal atrophy (VA) is a prevalent disorder in postmenopausal women that is characterized by decreased epithelial thickness, reduced vaginal maturation index (VMI) and increased vaginal pH. Current medical therapy consists of local or systemic replacement of estrogens. Objective The goal of this study was to understand, at a molecular level, the effect of estradiol (E2) on the vaginal epithelium. Methods Nineteen women were treated with E2 delivered through a skin patch at a dose of 0.05 mg/day for 12 weeks. The diagnosis of VA was confirmed by a VMI with ≤5% superficial cells and vaginal pH > 5.0. Vaginal biopsy samples were collected at baseline and after treatment. Differentially expressed mRNA transcripts in these biopsies were determined by microarray analysis. Results All 19 subjects had increased VMI (>5%) and/or reduced pH (≤5) following treatment. Most subjects also had increased serum E2 levels and reduced serum FSH levels. Transcriptional profiling of vaginal biopsies identified over 3000 E2-regulated genes, including those involved in several key pathways known to regulate cell growth and proliferation, barrier function and pathogen defense. Conclusions E2 controls a plethora of cellular pathways that are concordant with its profound effect on vaginal physiology. The data presented here are a useful step toward understanding the role of E2 in vaginal tissue and the development of novel therapeutics for the treatment of VA.

Development of Primordial Follicles in the Hamster: Role of Estradiol-17β

The role of E2 on primordial follicle formation was examined by treating neonatal hamsters with 1 or 2 microg estradiol cypionate (ECP) at age postnatal d 1 (P1) and P4 or by in vitro culture of embryonic d 15 (E15) ovaries with 1, 5, or 10 ng/ml estradiol-17beta (E2). The specificity of E2 action was examined by ICI 182,780. One microgram of ECP maintained serum levels of E2 within the physiological range, significantly reduced apoptosis, and stimulated the formation and development of primordial follicles. In contrast, 2 microg ECP increased serum E2 levels to 400 pg/ml and had significantly less influence on primordial follicle formation. In vivo, ICI 182,780 significantly increased apoptosis and caused a modest reduction in primordial follicle formation. The formation and development of primordial follicles in vitro increased markedly with 1 ng/ml E2, and the effect was blocked by ICI 182,780. Higher doses of E2 had no effect on primordial follicle formation but significantly up-regulated apoptosis, which was blocked by ICI 182,780. CYP19A1 mRNA expression occurred by E13 and increased with the formation of primordial follicles. P4 ovaries synthesized E2 from testosterone, which increased further by FSH. Both testosterone and FSH maintained ovarian CYP19A1 mRNA, but FSH up-regulated the expression. These results suggest that neonatal hamster ovaries produce E2 under FSH control and that E2 action is essential for the survival and differentiation of somatic cells and the oocytes leading to the formation and development of primordial follicles. This supportive action of E2 is lost when hormone levels increase above a threshold.

P-770: Influence of GnRH protocols on the estradiol serum level and number of mature oocytes (MII) retrieved

P-770: Influence of GnRH protocols on the estradiol serum level and number of mature oocytes (MII) retrieved

Effects of ascorbic acid supplementation on serum progesterone levels in patients with a luteal phase defect

Effects of ascorbic acid supplementation on serum progesterone levels in patients with a luteal phase defect

Ovariectomy and 17beta-estradiol modulate the levels of Alzheimer's amyloid beta peptides in brain.

To test whether female gonadal hormone status and estrogen modulate the metabolism of Abeta peptides in vivo. AD is a neurodegenerative disorder characterized by accumulation of aggregated forms of the 40- and 42-amino acid Abeta peptides (Abeta40 and Abeta42). Estrogen replacement therapy in postmenopausal women is associated with decreased risk for AD or delay in disease onset or both. The mechanism by which estrogen exerts this neuroprotective effect is elusive. 17beta-estradiol (E2) was shown to reduce the release of Abeta peptides by primary neuronal cultures of murine and human origin. For this purpose, four experimental sets of guinea pigs were used: intact animals, ovariectomized animals (ovx), and ovariectomized animals that received E2 at two different doses (ovx+low-dose E2 and ovx+high-dose E2). Brain Abeta40 and Abeta42 levels were assessed using Abeta40 and Abeta42-specific ELISA assays. Prolonged ovariectomy resulted in uterine atrophy and decreased serum E2 levels and was associated with a pronounced increase in brain Abeta levels. Total brain Abeta in the ovx animals was increased by 1. 5-fold on average as compared to intact controls. E2 treatment of ovariectomized animals led to uterine hypertrophy and a dose-dependent increase in serum E2 levels. In addition, both doses of E2 significantly reversed the ovariectomy-induced increase in brain Abeta levels. The high-dose E2 treatment did not lead to a further decrease in brain Abeta beyond that observed with the low-dose E2 treatment. Our results infer that cessation of ovarian estrogen production in postmenopausal women might facilitate Abeta deposition by increasing the local concentrations of Abeta40 and Abeta42 peptides in brain. In addition, our finding that E2 treatment is associated with diminution of brain Abeta levels suggests that modulation of Abeta metabolism may be one of the ways by which estrogen replacement therapy prevents or delays the onset of AD or both in postmenopausal women.

A randomized controlled study of the effects of 17Beta-estradiol-dydrogesterone on plasma homocysteine in postmenopausal women

Objective: To investigate the effects of oral 17β-estradiol (E2) -dydrogesterone on fasting plasma homocysteine concentrations in healthy postmenopausal women. Methods: We studied 27 postmenopausal women who were assigned randomly to either a treatment group ( n = 14) or a control group ( n = 13). During the first 12 months of the study, treatment consisted of oral E2, 1 mg daily, combined sequentially with dydrogesterone 5 or 10 mg (14 days per 28-day treatment cycle). Thereafter, women were treated with oral E2,2 mg daily, combined sequentially with dydrogesterone, 10 mg daily (14 days per 28-day treatment cycle) for a period of 3 months. The control group received no treatment. Fasting plasma total homocysteine concentrations were determined at baseline and 3, 12, and 15 months after study entry. Results: At baseline, plasma homocysteine levels did not differ between the groups. After 15 months of hormone treatment mean plasma homocysteine concentration was lowered by 12.6% compared with baseline ( P < .001; analysis of variance for repeated measures). Plasma homocysteine levels were not altered in the control group. The interaction between treatment and time for homocysteine levels was significantly different between the groups ( P < .001; analysis of variance for repeated measures). The decrease in plasma homocysteine levels correlated inversely with the increase in serum E2 levels after 3 and 12 months of hormone treatment ( r = −.54, P < .05 and r = −.56, P < .05, respectively). Conclusion: Plasma fasting homocysteine concentrations are lowered by E2-dydrogesterone therapy in postmenopausal women.

The Utility of a Midcycle Follicle-Stimulating Hormone Boost in Addition to Human Chorionic Gonadotropin for Timing of Follicle Aspiration in Unstimulated in vitro Fertilization Cycles

To analyze the effects and potential benefits of a single midcycle dose of follicle-stimulating hormone (FSH) prior to human chorionic gonadotropin (hCG) administration during unstimulated in vitro fertilization (IVF) cycles. Twenty-five cycles from 20 patients receiving 150 IU of FSH 42-44 h and 10,000 IU of hCG 34-36 h prior to follicle aspiration were compared to 110 cycles triggered with hCG alone. Serum E2 levels were significantly lower on the day of hCG treatment in the FSH-treated group (266 vs. 297 pg/ml). On the day after hCG administration, serum E2 was similar in both groups. Maximum follicular diameters the day of and the day after hCG treatment were similar as were the number of oocytes aspirated and embryos transferred, and clinical pregnancy rates in both groups. The number of cycles dropped due to premature luteinizing-hormone (LH) surge was 8% in the FSH group compared to 20% in the group treated with hCG alone. A midcycle FSH boost does not increase pregnancy success of unstimulated IVF cycles but does enhance the increase in serum E2 levels after hCG, thereby potentially allowing earlier hCG administration while incurring decreased cycle cancellation rates due to premature LH surges.

Androgen Inhibition of Vitellogenin Gene Expression in Tilapia (Oreochromis niloticus)

Treatment of mature female tilapia (Oreochromis niloticus) with high levels of androgen (17α-methyltestosterone, 17αMT) results in a pronounced decline in plasma vitellogenin levels as determined by gel electrophoresis. Total RNA extracted from livers of treated fish and vehicle-injected controls was analyzed by Northern and slot blot hybridization using an oligonucleotide complementary to a sequence in the 3′ end of tilapia vitellogenin mRNA. The probe revealed an mRNA of 6.5 kb in liver from the control mature female fish which was decreased by 85% by androgen treatment. As expected, estradiol (E2) treatment induced the 6.5-kb mRNA in mature male tilapia. The antiestrogen, tamoxifen, strongly decreased vitellogenin mRNA levels in mature females. Radioimmunoassay of serum from control and 17αMT-treated female tilapia showed a marked reduction in serum E2levels, from 11.4 ± 2.6 ng/ml in controls to 2.2 ± 0.13 ng/ml in treated fish. Tamoxifen, however, resulted in increased serum E2levels, probably by blocking E2negative feedback. The serum E2-lowering effect of 17αMT suggests an inhibitory site of action on gonadotropin production at the hypothalamic–pituitary axis, possibly through an androgen receptor or through an estrogen receptor after local aromatization of 17αMT.

Lower implantation rates in high responders: evidence for an altered endocrine milieu during the preimplantation period

To determine serum E2 and P levels around the time of implantation in normal and high IVF responders. In Vitro Fertilization program at the Instituto Valenciano de Infertilidad. Twenty-nine women undergoing IVF, who accepted to be studied daily, were classified according to the number of oocytes retrieved in normal (n = 16) and high responders (n = 13). Prospective study in which blood was drawn daily from the day of hCG administration (day 0) up to 7 days later (day 6). In vitro fertilization parameters (number of ampules, FSH-hMG, number of oocytes, fertilization rates, number of transferred embryos, implantation rates, and pregnancy rates); serum E2 and P levels during the 7 days of the study. Implantation rate was significantly higher in normal (18.5%) as compared with high (0%) responders. Estradiol and P levels were elevated significantly in high responders. The E2:P ratio was significantly different between normal and high responders during the preimplantation period. Pregnancy and implantation rates decreased as serum E2 levels increased on days 4 to 6 of the study. A different endocrine milieu between normal and high responders is detected by daily steroid measurements up to the preimplantation period, suggesting that this difference could be responsible for an impaired implantation in high responder patients undergoing IVF. An increase in serum E2 levels seems to be the cause of this difference.

Changes in serum sex steroid levels during megestrol acetate therapy.

We hypothesized that megestrol acetate (MA) may work on breast carcinoma by inducing changes in serum sex steroid levels. We prospectively measured levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone (DHEA), estrone (E1), and estradiol (E2) in 18 postmenopausal women before and during megestrol acetate therapy. MA significantly suppressed serum FSH, LH, DHEA and E1 levels. However, this was accompanied by a marked increase in serum E2 levels as measured by radioimmunoassay performed on whole serum. MA did not cross-react with the anti-E2 antibodies used in the assay. Elevated E2 levels also occurred in oophorectomized and/or adrenalectomized patients indicating the ovary and adrenal are not the source of the elevated E2 levels. We conclude that MA may be metabolized to oestrogenic compounds that crossreact with antibodies to E2, explaining the elevated E2 levels observed. The effects of these oestrogenic metabolites on breast carcinoma are unknown.