SEARCH · PubMed Health

Results for “ESTRADIOL, THERAPEUTIC”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources

PubMed1995

[Correlation of skinfold thickness with bone density and estradiol, FSH and prolactin level in a sample of 231 women].

Skin thickness was measured by means of ultrasound and correlated with the results of bone densitometry and hormonal parameters. Skin thickness and bone density were significantly correlated (p < 0.0001). These results indicated that not only bone, but also skin is a hormone-dependent organ, which responds to the menopausal decrease in sexual steroids. Hence, skin ultrasound, just like bone densitometry, can be useful implemented in the differential diagnostic procedure, as well as the therapy of the menopausal syndrome. Additionally, the estrogen-dependent postmenopausal decrease in collagen tissue can be assessed by ultrasound and a successful therapeutic outcome achieved by optimizing the dosage of estrogen substitution.

Bone Density↗

PubMed1989

Effect of an oral contraceptive in primary dysmenorrhea--changes in uterine activity and reactivity to agonists.

Mechanisms for the therapeutic effect of oral contraceptives in dysmenorrhea were studied by recording intrauterine pressure on the first day of menstrual bleeding in women with moderate to severe symptoms and after three weeks of oral contraceptive therapy (150 micrograms levonorgestrel + 30 micrograms ethinyl estradiol, daily). Spontaneous uterine activity and reactivity to intravenous injections of vasopressin (6 pmol/kg body weight; n = 8) or prostaglandin F2 alpha (12 nmol/kg body weight; n = 9) at the two sessions were compared. During the first recording when all women had dysmenorrhea, the uterine activity and reactivity to both agonists were pronounced. After therapy, when the women felt essentially no pain, a statistically significant decrease in spontaneous uterine activity in terms of total pressure area, frequency and amplitude of contractions was observed. The agonist injections induced less pain at the second recording, although the magnitude of responses, superimposed on the much smaller uterine activity at this time, were not significantly different from those at the first recording during dysmenorrhea. The mechanism of pain relief by oral contraception in dysmenorrhea could be a lesser impact of the decreased contractile activity on uterine blood flow, abolishing the local ischemia. A reduced uterine reactivity to agonists might also to some extent contribute to the therapeutic effect.

Adult↗

PubMed1989

A study of the effect of mifepristone (antiprogesterone) followed by prostaglandin on uterine activity and fetal heart rate in patients having a termination of pregnancy.

In the 72 h after a single oral dose of 400 mg of the antiprogesterone mifepristone, 12 out of 14 first and one second trimester fetuses had a slight increase in heart rate; 2 fetuses died and one aborted. During the same 72 h, uterine activity increased moderately, and was physiological with no increase in resting pressure. The treatment sensitized the uterus to prostaglandin (PG) about ten-fold. A low, 0.05 mg IM, dose of sulprostone caused the demise of 5 more fetuses and caused the onset of clinical abortion in less than 2 h. After a relatively short hypertonic phase uterine resting pressure fell to normal levels and active contractions occurred leading to expulsion of uterine contents. The plasma level of progesterone (P) remained unaltered after mifepristone treatment, but the levels of estradiol 17b (E2) and cortisol increased. The plasma level of mifepristone was 1640 +/- 424 ng. ml -1 at 72 h, and the substance was still detectable after one week.

Abortifacient Agents↗

PubMed2004

[Medication of the month. Angeliq: new hormonal therapy of menopause, with antialdosterone and antiandrogenic properties].

Following American randomised controlled epidemiologic studies (HERS, WHI), regulatory authorities have advised that postmenopausal hormone therapy, using minimal effective dosages, is indicated for the first line treatment of climacteric symptoms during a limited, and problem-related period of time, and for second line prevention of osteoporosis when a non-hormonal treatment cannot be used. Observation of a discrete increase in cardiovascular and breast cancer risk in hormone users currently appears to partly justify this rather strict attitude. We report here results of studies concerning a new continuous combination regimen (Angeliq), associating a "half-dose" estrogen (estradiol 1 mg/d) with potentially less thrombogenic impact than a standard (2 mg) dose, and the new progestin drospirenone (2 mg/d). The latter demonstrates a high level of endometrial safety as well as unique antialdosterone properties (reduction of symptoms related to water retention; potential cardioprotective effects) and consistent antiandrogenic properties, useful for both metabolic and clinical issues. Accordingly, Angeliq constitutes a new therapeutic approach, in good agreement with updated guidelines related to hormone replacement therapy.

Androstenes↗

PubMed2004

Pregnancy despite imminent ovarian failure and extremely high endogenous gonadotropins and therapeutic strategies: case report and review.

PURPOSE: To attempt ovulation induction in a woman with premature ovarian failure who had very high serum follicle stimulating hormone (FSH) levels (e.g., 164 mIU/ml) by merely using ethinyl estradiol without gonadotropins. METHODS: Ethinyl estradiol (20-40 microg) was used to lower serum FSH. Monitoring of follicular maturation was performed using sonography to determine follicle size and serum estradiol. Progesterone vaginal suppositories (200 mg twice daily) were used following demonstration of oocyte release from the follicle. RESULTS: Follicle maturation and ovulation was achieved in six of ten treatment cycles. A clinical pregnancy occurred in the ninth treatment cycle and a live delivery of a healthy baby occurred. CONCLUSIONS: Despite small ovaries, amenorrhea, and failure to have withdrawal menses following progesterone, absence of antral follicles on initial ultrasound, and consistently extremely high serum FSH, ovulation and pregnancy is possible by merely lowering the serum FSH.

Adult↗

PubMed2006

Estrogen receptor protein interaction with phosphatidylinositol 3-kinase leads to activation of phosphorylated Akt and extracellular signal-regulated kinase 1/2 in the same population of cortical neurons: a unified mechanism of estrogen action.

17Beta-estradiol (E2)-induced neuroprotection is dependent on mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K) signaling cascades. We sought to determine whether E2 neuroprotective mechanisms are mediated by a unified signaling cascade activated by estrogen receptor (ER)-PI3K interaction within the same population of neurons or whether E2 activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt are independent signaling events in different neuronal populations. Immunoprecipitation of E2-treated cortical neurons was conducted to determine a protein-protein interaction between ER and the PI3K regulatory subunit p85. Subsequently, cortical neurons were treated with E2 alone or in presence of MAPK inhibitors or PI3K inhibitors. Results of these analyses indicated a protein-protein interaction between ER and p85 that was time-dependent and consistent with the temporal profile for generation of Akt (pAkt) and ERK1/2 phosphorylation (pERK1/2). E2-induced phosphorylation of Akt, was first apparent at 10 min and maximal at 30 min. Simultaneously, E2-induced pERK1/2 was first apparent at 5-10 min and maximal at 30 min. Inhibition of PI3K completely blocked E2 activation of pAkt at 10 and 30 min and blocked E2 activation of ERK1/2 at 10 min, which revealed a PI3K-independent activation of ERK at 30 min. Double immunocytochemical labeling for pERK1/2 and pAkt demonstrated that E2 induced both signaling pathways in the same neurons. These results indicate a unified signaling mechanism for rapid E2 action that leads to the coordinated activation of both pERK1/2 and pAkt in the same population of neurons. Implications of these results for understanding estrogen mechanism of action in neurons and therapeutic development are considered.

Alzheimer Disease↗

PubMed1999

Delay of preterm delivery in sheep by omega-3 long-chain polyunsaturates.

A positive correlation has been shown between dietary intake of long-chain omega-3 fatty acids in late pregnancy and gestation length in pregnant women and experimental animals. To determine whether omega-3 fatty acids have an effect on preterm labor in sheep, a fish oil concentrate emulsion was continuously infused to six pregnant ewes from 124 days gestational age. At 125 days, betamethasone was administered to the fetus to produce preterm labor. Both the onset of labor and the time of delivery were delayed by the fish oil emulsion. Two of the omega-3-infused ewes reverted from contractions to nonlabor, an effect never previously observed for experimental glucocorticoid-induced preterm labor in sheep. Maternal plasma estradiol and maternal and fetal prostaglandin E2 rose in control ewes but not in those infused with omega-3 fatty acid. The ability of omega-3 fatty acids to delay premature delivery in sheep indicates their possible use as tocolytics in humans. Premature labor is the major cause of neonatal death and long-term disability, and these studies present information that may lead to a novel therapeutic regimen for the prevention of preterm delivery in human pregnancy.

Adrenocorticotropic Hormone↗

PubMed1984

Hormonal and receptor status in postmenopausal women with endometrial carcinoma before and after treatment with tamoxifen.

Twenty-four patients with endometrial carcinoma received tamoxifen (Nolvadex) for 7 days. Before and after administration, circulating hormones (estradiol, testosterone, progesterone, gonadotropins FSH and LH) were evaluated. Estrogen (ER) and progesterone receptors (PgR) in neoplastic tissue were also assayed. Our results show a net increase in PgR content and a significant decrease in gonadotropin levels after the treatment. The authors suggest that clinical trials be conducted using tamoxifen and progestins for adjuvant therapy after surgery of endometrial carcinoma and for the therapeutic approach of advanced carcinoma.

Carcinoma↗

PubMed2003

Comparative in vitro permeability of human vaginal, small intestinal and colonic mucosa.

Our previous experience with a continuous flow-through perfusion system has demonstrated its usefulness for studying diffusion kinetics of drugs across small intestinal mucosa for bioavailability/bioequivalence (BA/BE) studies. During the last decade, delivery of drugs to the colon for systemic absorption as well as for local delivery in certain colonic diseases, has been extensively investigated. For this reason, we sought to assess the in vitro comparative permeability of human vaginal, small intestinal and colonic mucosa using a flow-through perfusion method. It was clear from our studies that human colonic epithelium was statistically significantly (P<0.05) more permeable to water, 17beta-estradiol, arecoline and arecaidine than intestinal mucosa. However, both these mucosae were statistically significantly less permeable to the above four permeants than human vaginal mucosa. As previously shown for small intestinal mucosa, the low in vitro permeability of colonic mucosa to drugs with molecular weight >300Da may necessitate using other epithelial membranes, e.g. vaginal mucosa, as alternative barriers for in vitro BA/BE studies. We also concluded that the flow-through mucosal perfusion system used in our laboratory is therefore also potentially useful for determining the permeability of a therapeutic agent from the colon for registration purposes.

Adult↗

PubMed1989

Administration of pure follicle-stimulating hormone during gonadotropin-releasing hormone agonist therapy in patients with clomiphene-resistant polycystic ovarian disease: hormonal evaluations and clinical perspectives.

Nine women with chronic anovulation caused by polycystic ovarian disease, which was unresponsive to clomiphene citrate therapy, were given a gonadotropin-releasing hormone agonist (buserelin) to induce pituitary desensitization. After 4 weeks induction of ovulation was attempted with a step-up administration of urinary follicle-stimulating hormone. Buserelin treatment was discontinued only in the presence of a positive pregnancy test result. Different responses were observed between the first and subsequent cycles. Whereas estradiol production and follicular growth were closely correlated in the first attempt, we recorded a dissociation between these two parameters of ovarian response during subsequent stimulations. Four clinical pregnancies occurred in these nine patients, and there was one abortion. This therapeutic approach can be successfully used to induce ovulation; however, prolonging pituitary suppression between treatment cycles changes the type of ovarian response and is not followed by better results.

Adult↗

PubMed1993

Evidence for estrogen receptor-linked calcium transport in the intestine.

Intestinal calcium malabsorption in postmenopausal osteoporotic women is often linked indirectly to decreased serum 1,25(OH)2 vitamin D or to intestinal resistance to its action, rather than directly to the low circulating estrogen that results following menopause. The studies presented indicate that the intestinal mucosal cells of rats contain estrogen receptor immunoreactivity, express the mRNA for estrogen receptors, and respond directly to 17 beta-estradiol with enhanced calcium transport that is suppressed by gene transcription and protein synthesis inhibitors. These findings suggest that estrogen has a physiological role in the regulation of intestinal calcium absorption and that its deficiency in postmenopausal osteoporosis, and following therapeutic oophorectomy, may result directly in calcium malabsorption that is believed to be an important factor in the bone loss that occurs in these conditions.

Animals↗

PubMed2003

Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection.

Female animals are protected from many forms of neurological injury and degeneration relative to their male counterparts, in part attributable to their native estrogens. We hypothesized that estradiol aromatized from precursor androgens via the cytochrome P450 aromatase contributes to ischemic neuroprotection in the female. Female homozygous aromatase knock-out (ArKO) mice and randomly cycling, wild-type (WT) female littermates were treated with reversible middle cerebral artery occlusion (90 min; 22 hr reperfusion). Total and regional ischemic damage was greater in female ArKOs (total, 33.5 +/- 4.8%; cortical, 47.4 +/- 5.7%; striatal, 44.8 +/- 7.8%) compared with WT (total, 14.2 +/- 5%; cortical, 14.2 +/- 4.5%; striatal, 17.5 +/- 8%). Baseline blood pressure and intra-ischemic cortical perfusion were comparable in knock-outs and WT, suggesting that vascular factors do not explain ArKO ischemic sensitivity. Injury was smaller in ovariectomized WT than in ArKO, emphasizing that extragonadal local estradiol plays a critical role in females. Similar increases in cortical and striatal damage were observed in female WT mice chronically treated with the aromatase inhibitor fadrozole compared with vehicle-treated control mice. Restoration of plasma 17beta-estradiol to physiological levels completely reversed the ArKO female's susceptibility to injury. These findings indicate that the biosynthetic enzyme P450 aromatase is key to endogenous neuroprotection in females and suggest that enhancing local, nongonadal estrogen formation could have therapeutic implications is ischemic neuropathology.

Animals↗

PubMed2005

Histone deacetylase inhibitors induce differentiation of human endometrial adenocarcinoma cells through up-regulation of glycodelin.

Histone reversible acetylation, which is controlled by histone acetyltransferases and deacetylases, plays a fundamental role in gene transcription. Histone deacetylase inhibitors (HDACIs), such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), have been characterized not only as anticancer drugs, but also as cytodifferentiation-inducing agents. In human endometrium, postovulatory production of progesterone directs estrogen-primed endometrial glandular cells to differentiate and thereby produce a number of unique bioactive substances, including glycodelin, that are critical for implantation at the secretory phase of the menstrual cycle. In this study, we show that TSA and SAHA, belonging to the hydroxamic acid group of HDACIs, can induce the phenotype of a human endometrial adenocarcinoma cell line, Ishikawa (originally derived from the glandular component of the endometrium), to differentiate to closely resemble normal endometrial epithelium in a time- and dose-dependent manner, as determined by morphological changes, synthesis of glycogen, and expression of secretory phase-specific proteins, including glycodelin. The proliferation- and differentiation-modulating effects elicited by TSA and SAHA at their optimal concentrations were comparable or more potent than those exerted by combined treatment with progesterone and estradiol. Furthermore, the gene silencing of glycodelin by small interference RNA resulted in the blockade of HDACI-induced differentiation in Ishikawa cells, suggesting the requirement for glycodelin for endometrial epithelial differentiation. Our results collectively indicate that TSA and SAHA are potent differentiation inducers for endometrial glandular cells, providing a clue for a possible therapeutic strategy to modulate endometrial function by targeting glycodelin.

Adenocarcinoma↗

PubMed1992

The Lobund-Wistar rat model of prostate cancer.

Two models of preventable metastasizing autochthonous prostate adenocarcinoma (PA) have been described in Lobund-Wistar (L-W) rats: spontaneous PAs that develop at a mean age of 26 months; and induced PAs that develop at a mean time of 10.5 months. Both are similar in many respects to the counterpart disease in man. PAs develop spontaneously, and by induction through a combination of N-methyl-N-nitrosourea (MNU)/testosterone treatments. Our investigations with L-W rats show that PA is manifested spontaneously in 26% of aged L-W rats, and by induction in approximately 90% of younger rats. It is characterized by metastatic adenocarcinoma initiated in, and expanding from, the dorso-lateral and anterior lobes, and occasionally in the seminal vesicles. It is regulated by genetic, hormonal, and age-related mechanisms. Spontaneous PAs are prevented by life-long moderate (25%) diet restriction and, in rats at risk of developing induced PA, by early treatments with estradiol, with dihydrotestosterone, with a retinoid, and by castration. While the "premalignant" stages of induced tumorigenesis are susceptible to intervention, the overtly malignant stage resists therapeutic trials with the same agents and procedures. The transition from dependency to autonomy has not yet been defined.

Adenocarcinoma↗

PubMed2000

Apoptosis in mammary gland and cancer.

Homeostasis in normal tissue is regulated by a balance between proliferative activity and cell loss by apoptosis. Apoptosis is a physiological mechanism of cell loss that depends on both pre-existing proteins and de novo protein synthesis, and the process of apoptosis is integral to normal mammary gland development and in many diseases, including breast cancer. The mammary gland is one of the few organ systems in mammals that completes its morphologic development postnatally during two discrete physiologic states, puberty and pregnancy. The susceptibility of the mammary gland to tumorigenesis is influenced by its normal development, particularly during stages of puberty and pregnancy that are characterized by marked alterations in breast cell proliferation and differentiation. Numerous epidemiologic studies have suggested that specific details in the development of the mammary gland play a critical role in breast cancer risk. Mammary gland development is characterized by dynamic changes in the expression profiles of Bcl-2 family members. The expression of Bcl-2 family proteins in breast cancer is also influenced by estradiol and by progestin. Since the ratio of proapoptotic to antiapoptotic proteins determines apoptosis or cell survival, hormone levels may have important implications in the therapeutic prevention of breast cancer.

Animals↗

PubMed2000

Effect of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats.

The effects of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats were examined to evaluate its potential use as a therapeutic agent for osteoporotic fractures. Three months postovariectomy, bilateral tibial shaft fractures were induced and stabilized by intramedullary nailing with Kirschner wires. Saline, 17beta-estradiol (Sigma Chemical Corp, St Louis, Mo), or recombinant human parathyroid hormone (1-84) (Korean Green-Cross Pharm Corp, Seoul, Korea) was given once a day for 30 consecutive days during fracture healing. Fracture healing was assessed by morphometric and mechanical analysis of fracture callus. Intermittent parathyroid hormone administration increased the morphometric and mechanical parameters in a dose-dependent manner. A bone-resorption inhibiting agent, 17beta-estradiol did not offer advantage in terms of fracture healing in ovariectomized rats. Findings suggest intermittent parathyroid hormone administration may benefit osteoporosis and fracture.

Animals↗

PubMed1990

The effects of estradiol and progesterone on reproductive tract atrophy and tissue adrenergic indices in diabetic C57BL/KsJ mice.

The diabetes-associated changes in tissue norepinephrine (NE) concentrations and related adrenergic receptor types were correlated with changes in blood glucose and serum insulin levels in 8- to 16-week-old C57BL/KsJ-db/db mice relative to corresponding age-matched control (+/?) parameters. In addition, the ability of estradiol and progesterone treatments to modify the diabetes-related adrenergic imbalance was investigated. Tissue (i.e., ovarian, uterine, pancreatic, and adrenal) NE levels were determined by high-performance liquid chromatography and compared with the associated changes in tissue alpha 1,2 and beta-adrenergic membrane receptor populations. All db/db mice exhibited overt hyperglycemia, hyperinsulinemia, and obesity relative to controls between 8 and 16 weeks of age. Tissue NE levels in diabetics were either similar to, or elevated, as compared with those of age-matched controls. Although the alpha 1 and beta receptor populations (except liver) were similar in 16-week-old groups, alpha 2 receptor populations in db/db mice were elevated relative to controls. Chronic estradiol therapy effectively counteracted the diabetes-induced elevations in tissue NE and influenced all adrenergic receptor populations, normalizing both parameters to control levels as well as modifying the hyperglycemia, but not the hyperinsulinemic component, of the diabetes-obesity syndrome in this species. Chronic progesterone treatment was found to be less effective in modulating these systemic and adrenergic parameters in diabetics relative to oil- or estradiol-treated mice. These data demonstrate that a marked modification in tissue adrenergic parameters occur in association with the overt expression of the diabetes mutation in this species. The ability of estradiol treatment to normalize both blood glucose levels and tissue adrenergic parameters in C57BL/KsJ-db/db mice indicates that a direct association between systemic and cellular counter-regulating influences, relative to the severity of the Type II diabetic condition, exists in this species. The therapeutic correction of these metabolic problems by ovarian steroid hormones suggests the existence of a causal relationship between cellular glucose homeostasis and steroid action in the diabetic model.

Animals↗

PubMed1999

Effect of estrogen on aortic function in postmenopausal women.

We hypothesized that estrogen may alter aortic elastic properties. The aortic pressure-diameter relation was obtained in 20 postmenopausal women, 10 without (group 1) and 10 with (group 2) proven coronary artery disease, before and after intravenous administration of 10 micrograms of 17beta-estradiol. Instantaneous aortic diameter was measured by an intravascular catheter developed in our institution simultaneously with aortic pressure at the same aortic level with a catheter-tipped micromanometer. At baseline, elastic properties of the aorta were decreased in group 2 compared with group 1. Compared with baseline, aortic distensibility was increased in both groups (P < 0.01 and P < 0.05 for groups 1 and 2, respectively) after estrogen administration, whereas the pressure-diameter loop was shifted downward along a different hypothetical line of elasticity, suggesting active changes in the aortic elastic properties. Furthermore, a significant reduction in wave reflection was found in both groups (P < 0.001). This action may contribute to the beneficial effects of estrogen on the cardiovascular system and may have future therapeutic implications in postmenopausal women.

Aged↗