PubMed Health⌕ Search

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 415 records · Page 23Linked to original sources
PubMed1992

The prognostic importance of the number of oocytes retrieved and estradiol levels in poor and normal responders in in vitro fertilization (IVF) treatment.

A low response to ovarian stimulation in in vitro fertilization poses a unique therapeutic challenge. Gonadotropin-releasing hormone agonists (GnRHa) have been suggested as a modality for treatment of this condition. In this study, we analyzed the results of 880 in vitro fertilization treatment cycles with respect to modality of ovarian stimulation, degree of hormonal response, and number of oocytes retrieved. In patients with estradiol (E2) levels less than 501 pg/ml on the day of human chorionic gonadotropin administration, 27% pregnancy rate was achieved with clomiphene citrate (CC) combined with human menopausal gonadotropin (hMG), compared to 15.1% (P less than 0.005) with hMG alone and 20.8% (NS) with GnRHa and hMG. Pregnancy rates were not lower in these patients compared to patients with higher estradiol levels in the different stimulation protocols, but pregnancy rates were significantly lower in cycles during which three or fewer oocytes were retrieved, compared to those in which four or more oocytes were retrieved (10.8 vs 23.8%; P less than 0.0005). In low-retrieval cycles pregnancy rates actually decreased with increasing levels of estradiol. Our results indicate that the number of oocytes retrieved is a better prognostic parameter than E2 levels in predicting the outcome of in vitro fertilization treatment and that GnRHa in the long protocol do not seem to be superior to CC combined with hMG for the treatment of poor responders.

Biomarkers↗
PubMed1986

Bioequivalence of norethindrone and ethinyl estradiol for two different weight tablets with the same hormonal content.

Two tablets of differing weights, 100 mg (A) and 50 mg (B), of an oral contraceptive drug (OC) were compared with each other and to a solution (C) of the same components. The composition of the OC consisted of 1 mg of norethindrone (NET) and 0.035 mg of ethinyl estradiol (EE2). Both tablets were shown to differ from the solution, which was more rapidly absorbed, but were not significantly different from each other. Formulation means for NET and EE2, for each of the two products, were similar. Application of an interval test for the ratio of computed parameters demonstrated equivalence of the two formulations with respect to 0-24 hr area under the curve (AUC24) and total area under the curve (AUC+o+) for both NET and EE2 and with respect to concentration maximum (Cmax) for EE2. The data support the hypothesis for bioequivalence of the two formulations with respect to total absorption.

Absorption↗
PubMed2001

High-dose estradiol improves cognition for women with AD: results of a randomized study.

OBJECTIVE: To characterize the cognitive and neuroendocrine response to treatment with a high dose of estrogen for postmenopausal women with AD. METHODS: Twenty postmenopausal women with AD were randomized to receive either 0.10 mg/day of 17 beta-estradiol by skin patch or a placebo patch for 8 weeks. Subjects were evaluated at baseline, at weeks 3, 5, and 8 during treatment, and again 8 weeks after treatment termination. During each visit, cognition was assessed with a battery of neuropsychological tests, and blood samples were collected to measure plasma estradiol as well as several other neuroendocrine markers of interest. RESULTS: Significant effects of estrogen treatment were observed on attention (Stroop Color Word Interference Test), verbal memory (Buschke Selective Reminding Test), and visual memory (Figure Copy/Memory). In addition, women treated with estrogen demonstrated improved performance on a test of semantic memory (Boston Naming Test) compared with subjects who received a placebo. Estrogen appeared to have a suppressive effect on the insulin-like growth factor (IGF) system such that plasma concentration of IGF binding protein-3 was significantly reduced and plasma levels of estradiol and IGF-I were negatively correlated during estrogen treatment. CONCLUSIONS: Administration of a higher dose of estrogen may enhance attention and memory for postmenopausal women with AD. Although these findings provide further clinical evidence to support a cognitive benefit of estrogen for women with AD, studies evaluating the effect of estradiol administration, in particular, using larger sample sizes and for longer treatment durations are warranted before the therapeutic potential of estrogen replacement for women with AD can be firmly established.

Aged↗
PubMed2002

Efficacy and tolerability of pulsed estrogen therapy: a 12-week double-blind placebo-controlled study in highly symptomatic postmenopausal women.

OBJECTIVE: To confirm the efficacy and safety of pulsed estrogen therapy, a transient daily hormone exposure, for climacteric symptoms in highly symptomatic postmenopausal women. PATIENTS AND METHODS: In this multicenter, double-blind, parallel-group study, early postmenopausal women with at least seven moderate to severe vasomotor symptoms per day were randomized to receive intranasal estradiol, 150 or 300 microg/day, or placebo, for 12 weeks. The primary outcome measure was the mean daily number of moderate to severe vasomotor symptoms, as recorded in patient diaries. RESULTS: A total of 165 patients were randomized. The mean daily number of moderate to severe vasomotor symptoms decreased significantly more (p < 0.001) in the 150-microg/day (-7.86) and 300-microg/day (-9.39) groups than in the placebo group (-5.22). The decrease reached significance more rapidly with the 300-microg/day dose (from week 2) than with the 150-microg/day dose (from week 8). The rate of emergent adverse events with both doses was similar to that with placebo. CONCLUSIONS: Pulsed estrogen therapy, achieved by intranasal estradiol 150 microg/day and 300 microg/day, significantlyreduced the incidence of moderate to severe vasomotor symptoms, compared with placebo. The 300-microg/day dose demonstrated a greater and more rapid therapeutic effect, with no clinically significant difference in tolerability, compared with the 150-microg/day dose, and therefore offers the best efficacy/safety ratio when initiating treatment with intranasal estradiol.

Administration, Intranasal↗
PubMed1998

Acetaminophen alters estrogenic responses in vitro: stimulation of DNA synthesis in estrogen-responsive human breast cancer cells.

A limited number of studies have investigated the estrogenic potential of acetaminophen but none has reported its effects on breast cells. Many compounds that alter estrogen-mediated processes in various tissues contain p-phenolic moieties. Acetaminophen is a commonly used analgesic/antipyretic that also contains a p-phenol. This study tested the hypothesis that therapeutic concentrations of acetaminophen alter estrogen-responsive human breast cancer cell DNA synthesis. To this end, a modified E-screen assay was developed to determine the response to acetaminophen of two dichotomous types of human breast cancer cell lines: estrogen-responsive (MCF7, T47D, ZR-75-1) and estrogen-nonresponsive (MDA-MB-231, HS578T). Cells were placed in estradiol-free medium and then exposed to 3 nM estradiol or 0.03-1 mM acetaminophen. The proliferative response was assessed by determining [3H]thymidine incorporation into DNA and by determining the percentage of cells in the DNA synthesis (S) phase of the cell cycle. Concentrations of acetaminophen commonly attained in human plasma with therapeutic doses of this drug (approximately 0.1 mM) were found as effective as estradiol in stimulating DNA synthesis in estrogen-responsive breast cancer cells. Higher acetaminophen concentrations (1 mM) stimulated estrogen-responsive cells to a lesser extent. The combination of estradiol and acetaminophen did not stimulate DNA synthesis in estrogen-responsive cells more than either agent alone. Neither acetaminophen nor estradiol stimulated DNA synthesis in estrogen-nonresponsive human breast cancer cells. These novel findings demonstrate that therapeutic acetaminophen concentrations specifically stimulate estrogen-responsive breast cancer cell DNA synthesis, suggesting that this drug may exert estrogenic effects.

Acetaminophen↗
PubMed2001

The control of progesterone receptor expression in MCF-7 breast cancer cells: effects of estradiol and sex hormone-binding globulin (SHBG).

Estradiol controls the gene transcription and expression of many proteins in breast cancer cells, like the progesterone receptor, PR, that is up-regulated by the hormone. Moreover, estradiol is one of the crucial factors inducing the proliferation of breast cancer cells. Sex Hormone-Binding Globulin (SHBG), the plasma carrier for both estradiol and androgens, inhibits the estradiol-induced growth of MCF-7 cells (estrogen-dependent breast cancer cells), through its membrane receptor (SHBG-R), cAMP and PKA. The anti-estrogenic effect of SHBG, which has been described only as far as cell proliferation is concerned, could also play a meaningful role in the estradiol control of other factors in breast cancer cells. In the present study, the effect of SHBG on the estradiol control of PR expression (both mRNA and protein) and function (receptor binding capacity) in MCF-7 cells was examined. SHBG inhibited the estradiol-induced up-regulation of PR mRNA as well as protein level and function. Moreover, the effect of SHBG on estradiol control of PR expression and function was showed to be specific and mediated by PKA. The intermediacy of PKA in the PR expression control, together with the observation that it is effective in the condition in which the SHBG receptor is activated, supports the hypothesis that the anti-estrogenic effect of SHBG could be receptor-mediated. The ability of SHBG to inhibit estradiol action in a specific way in estrogen-dependent breast cancer cells has, therefore, to be taken into account for the development of future therapeutic strategies.

Blotting, Western↗
PubMed1988

Cyclosporine differentially affects estrogen and progestin synthesis by rat granulosa cells in vitro.

Potential side-effects of the immunosuppressive drug cyclosporine (also cyclosporin A, CsA) on ovarian endocrine function have been investigated using granulosa cells isolated from immature estrogen-primed rats and cultured in a chemically defined medium. The FSH-dependent differentiation of steroidogenic pathways for estrogen and progestin secretion was shown to be differentially affected by CsA in vitro, at drug concentrations that approximate immunosuppressive concentrations in blood of humans or animals. CsA at 0.1-1 microgram/ml synergistically enhanced FSH-stimulated aromatase activity as measured by the conversion of exogenous testosterone to 17 beta-estradiol, while production of the progestins (progesterone + 20 alpha-hydroxypregn-4-en-3-one + pregnenolone) was little affected at up to 0.1 microgram/ml CsA and reduced at higher concentrations. CsA alone did not stimulate basal steroid secretion. The action of CsA to augment FSH-stimulated induction of aromatase activity was seen both in the presence or absence of testosterone. The effects of CsA (1 microgram/ml), either stimulatory on aromatase activity or inhibitory on progestin secretion, were in general increased with greater times of cell exposure throughout the culture period, although the temporal effects on 17 beta-estradiol and the progestins were not identical following delayed addition or removal of CsA from the culture medium. Higher concentrations of CsA (3-10 micrograms/ml) were generally toxic to granulosa cells as indicated by marked decreases in 17 beta-estradiol and progestin secretion and in incorporation of [3H]leucine. These results suggest that therapeutic concentrations of CsA might directly influence ovarian function by differentially modulating the FSH-dependent steroidogenic pathways of granulosa cells.

Animals↗
PubMed2001

Chemoprevention with aromatase inhibitors--trial strategies.

Estrogen and its catechol metabolites from both the circulation and synthesized within the breast are important in the pathogenesis of breast cancer. Blocking estrogen's effects on the breast with selective estrogen receptor modulators (SERMS) is an ongoing strategy. Thus, tamoxifen and raloxifene reduce risk as monotherapy. Aromatase (estrogen synthetase) inhibitors are a logical alternative to SERMS. To date, SERMS have demonstrated reduction only in estrogen-progesterone receptor positive cancers without reduction in receptor negative tumors. By inhibiting the parent estrogens and their catechol metabolites, true prevention of cancer initiation might occur and reduction not only in the receptor positive but also negative tumors might result. Ongoing adjuvant breast cancer trials are exploring aromatase inhibitors as alternatives to tamoxifen, or in sequence or in combination with tamoxifen. Relative efficacies including reduction in contralateral breast cancer, toxicities and end-organ effects and impact on quality of life, are being explored. Data from these trials will help to guide future chemoprevention strategies. Proof of principal trials in 'high risk' cohorts such as premalignant breast lesions, dense screening mammograms, high plasma estradiol levels or increased bone density are already ongoing. Issues such as dose, schedule, therapeutic index and mono versus combination therapy are important to define.

Animals↗
PubMed1985

Interruption of first trimester human pregnancy following Epostane therapy. Effect of prostaglandin E2 pessaries.

The effect of Epostane, a competitive inhibitor of the 3 beta hydroxy steroid dehydrogenase enzyme system in combination with prostaglandin E2 (PGE2) for induction of abortion in early first trimester pregnancy has been studied in a group of 20 women awaiting termination of pregnancy. The women were consecutively assigned to four treatment groups. The first group was treated with PGE2 alone, administered vaginally as a lipid based (Witepsol) pessary. The remaining three groups received Epostane at differing doses for 5 days, and were treated with PGE2 on the fourth day. Significant falls in serum progesterone and oestradiol occurred in the Epostane-treated patients. Abortion was induced in one of the five control patients and in three of 10 patients treated with low doses (300-400 mg) of Epostane. Intrauterine pressure monitoring showed an increased reactivity to PGE2 in the treated groups. At the highest dose (600 mg) of Epostane, serum progesterone and oestradiol showed the greatest decline to 8% and 21% of the pretreatment values, a prompt and sustained pressure response occurred to PGE2 and abortion was induced in all five patients. A critical degree of progesterone suppression appears to sensitize the myometrium to exogenous prostaglandin. This combined treatment is an effective method of early pregnancy termination and may have a role in the management of mid-trimester abortion.

3-Hydroxysteroid Dehydrogenases↗
PubMed1977

Endometrial screening of asymptomatic women by irrigation technique in the private gynecology office.

A study was made of 201 asymptomatic women over age 40 (range, 40-74 years) who underwent uterine sounding and endometrial screening by the negative-pressure jet irrigation technique, without anesthesia, in private gynecologists' offices. Introduction of the irrigator was accomplished in 88 percent of these patients. In 97 percent of the successful irrigations, the specimens obtained were satisfactory for cytologic and histologic diagnosis of neoplasia. No occult endometrial carcinomas were discovered. The factors which interfered with endometrial screening by these methods are analyzed. Cervical stenosis prevented endometrial irrigation in 13 of the 24 unsuccessful attempts. Acceptance by the patients was high, in that 74.2 percent reported slight or no discomfort and only 4.7 percent complained of severe discomfort. Although 12.5 percent experienced pelvic cramping after irrigation, no other significant side effects were observed. The results of this investigation indicate the feasibility of using the endometrial irrigation technique for massive screening studies of asymptomatic women who are at risk for the development of endometrial carcinoma.

Adult↗
PubMed2005

Effect of a triphasic oral contraceptive on drug-metabolizing enzyme activity as measured by the validated Cooperstown 5+1 cocktail.

The effects of a common oral contraceptive preparation on the activity of 7 drug-metabolizing enzymes were investigated using the validated Cooperstown 5+1 Cocktail. In a randomized crossover fashion, 10 premenopausal women received caffeine, dextromethorphan, omeprazole, intravenous midazolam, and warfarin + vitamin K with and without a triphasic oral contraceptive (ethinyl estradiol 35 microg) and varying doses of daily norgestimate (0.18, 0.215, and 0.25 mg). Bioequivalence testing showed nonequivalence in drug versus no-drug treatment on the activity of drug-metabolizing enzymes (as reflected by metabolite ratios following probe drug administration); the activity of CYP1A2, CYP2C19, and NAT-2 decreased following the oral contraceptive, whereas the activity of CYP2C9 and CYP2D6 increased. No effects on xanthine oxidase or hepatic CYP3A were seen. Application of a non-parametric statistical testing approach revealed a significant difference only for CYP1A2 and CYP2C19. This triphasic oral contraceptive may have a clinically significant effect on the activity of some drug-metabolizing enzymes.

Adult↗
PubMed1989

Serum concentration and urinary excretion of the luteinizing hormone-releasing hormone agonist buserelin in patients with endometriosis.

We studied the pharmacokinetics of iv and intranasally administered buserelin, a LHRH agonist peptide, in 14 women with endometriosis. Serum and urinary buserelin concentrations were determined by specific RIA (buserelin antiserum AS-639). Intact buserelin and the metabolites in urine were separated by reverse phase high performance liquid chromatography and measured by RIA. The mean serum buserelin concentrations were 101 +/- 33 (+/- SD) ng/mL 20 min and 1.12 +/- 0.12 ng/mL 360 min after its iv injection in 6 women, and the mean elimination half-life between 20 and 360 min was 51 min. In serum, intact buserelin was the main constituent (10 min, 90%; 120 min, 74%; 360 min, 52%), and the major metabolite was the buserelin-(5-9) pentapeptide (10 min, 0.6%; 120 min, 19%; 360 min, 12%). In the urine collected 0-1 h after buserelin administration, intact buserelin was 66% and the 5-9 pentapeptide was 28% of the total excretion. In the urine collected between 6-24 h after buserelin administration, intact buserelin accounted for 67% and the 5-9 pentapeptide for 32% of the total excretion. The urinary buserelin concentration was 1345 +/- 156 micrograms/g creatinine 1 h and 25 +/- 5 micrograms/g creatinine 6-24 h after buserelin administration. Serum LH, FSH, and estradiol concentrations increased acutely up to 10-fold above basal values; the mean peak LH, FSH, and estradiol values occurred at 180-240 min, 240 min, and 24 h, respectively. In therapeutic studies with buserelin nasal spray in 5 women, serum concentrations of 0.9-1.4 ng/mL were found 15 min after a single dose of 300 micrograms, intranasally, and the urinary excretion was 2.52-3.68 micrograms/24 h during daily administration of 3 doses of 300 micrograms at intervals of 8 h. These results confirm that buserelin is slowly inactivated and remains available to pituitary receptors for a prolonged period after its iv or intranasal administration.

Administration, Intranasal↗
PubMed2003

Effects of estrogen on brain development and neuroprotection--implications for negative symptoms in schizophrenia.

Increasing evidence during the last few years suggests that there are gender-specific differences in schizophrenia, influencing the age of onset, treatment outcome and the prevalence of negative symptoms. With respect to the latter in postmortem brain and cerebrospinal fluid of schizophrenic patients with negative symptoms a reduction of dopaminergic activity became evident. Measures of noradrenergic activity, dopamine beta-hydroxylase and the metabolite MHPG, appear to decrease with brain atrophy seen in patients with negative symptoms. Serotonergic activity tends to be low in patients with impaired cognitive function as is seen in negative schizophrenia. In these patients ventricular enlargement is associated with the severity of negative symptoms, low monoamine activity and low cerebral glucose metabolism. On the other hand atypical antipsychotic drugs that modulate also glutamate receptor activity, suggest an additional alternative mechanism of antipsychotic action beyond aminergic neurotransmitters. These drugs improve glutamatergic transmission and decrease negative symptoms; this suggests a glutamatergic deficiency as an extension of the dopamine model. The glutamate-dopamine interaction illustrates the importance of cross-talk between projections to the cortex, striatum, and lower brainstem for the expression of negative symptomatology. On the other hand, estradiol-17beta the most potent female sex hormone influences not only primary and secondary sexual characteristics but also embryonal and fetal growth as well as development of the brain aminergic networks, which are involved in schizophrenia. Estradiol-l7beta possesses neuroprotective properties, which are relevant for the course of schizophrenia and this may explain the pronounced gender differences with respect to progression and therapeutic response of schizophrenia. The present review attempts an update and synthesis of the information about the hormonal influence on neuronal pathways in negative symptoms of schizophrenia. It shows that estradiol-l7beta influences transporters and receptors as well as the morphological appearance of neuronal systems and that it may be an integral part of the neuroprotective system ameliorating schizophrenia.

Biogenic Monoamines↗
PubMed1986

Estrogens and osteoarthritis.

Clinical and laboratory observations suggest that a relationship exists between sex hormones and the development of osteoarthritis. The mechanisms whereby these hormones influence the pathophysiology of osteoarthritis have been explored. Tamoxifen, an estrogen antagonist, reduced erosive changes in meniscectomy-induced osteoarthritis in rabbits. By contrast, estradiol worsened it. There was no effect of either agent on the incidence of osteophytes in this model. Both estradiol and tamoxifen affected proteoglycan, prostaglandin, and proteoglycanase production by cartilage components. These observations suggest that cartilage is a sex hormone-sensitive tissue. This may have therapeutic implications in the future.

Animals↗
PubMed2005

Tamoxifen blocks estrogen-induced B cell maturation but not survival.

Estrogen treatment has been shown not only to exacerbate disease activity and accelerate death in spontaneous murine models of lupus but also to induce a lupus-like phenotype in non-spontaneously autoimmune mice. In mice transgenic for the H chain of an anti-DNA Ab, estrogen rescues naive autoreactive B cells that normally are deleted and causes them to mature to a marginal zone phenotype. Estrogen further leads to the activation of this population causing an elevation of serum anti-DNA Ab titers and renal disease. This study was designed to evaluate the therapeutic potential of tamoxifen, a selective estrogen receptor modulator, on estrogen-induced lupus. Mice treated with both estradiol and tamoxifen showed no elevation in anti-DNA Ab titers and consequently no glomerular IgG. The DNA-reactive B cell population that is rescued by estrogen was present in an anergic state in mice treated with both estradiol and tamoxifen. Estradiol enhances transitional B cell resistance to apoptosis and expands the population of marginal zone B cells; tamoxifen did not impede the enhanced resistance to apoptosis, but prevented the development of autoreactive cells as marginal zone B cells. Thus, estrogen-induced autoimmunity proceeds through two distinct molecular pathways, one affecting survival and the other maturation. Activation, but not survival, of autoreactive B cells can be abrogated by tamoxifen. Drugs that modulate even some of the effects of estrogen may be beneficial in patients with lupus. Eventually, understanding the pathways involved in survival and activation of autoreactive B cells will permit the development of therapeutics that target all relevant pathways.

Animals↗
PubMed1997

Transcriptional regulation of the human 'leukemia inhibitory factor' gene: modulation by glucocorticoids and estradiol.

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine implicated in various pathological conditions, such as rheumatoid arthritis and osteoporosis. Despite its possible importance as a therapeutic target, very little is known about the regulation of human LIF. In particular, its regulation at the promoter level has not been studied so far, and was, therefore, the focus of the present work. After showing that Jurkat T lymphoma cells can be induced to express endogenous LIF mRNA, we used this cell line as a model to study the regulation of the human LIF promoter in transient transfection assays. For this purpose, a 666 bp fragment of the human LIF 5'-flanking region, amplified from genomic DNA by nested polymerase chain reaction (PCR), was used for the construction of a luciferase reporter plasmid (hLIF666-Luc). In unstimulated Jurkat cells, the human LIF promoter showed low constitutive activity. The promoter was induced upon stimulation with phorbol ester (TPA). Combined stimulation with TPA and the calcium ionophore ionomycin resulted in strong synergistic induction of luciferase activity from the LIF promoter. Transfection experiments with deletion constructs (hLIF274-Luc and hLIF82-Luc) located the region required for this induction to a 192 bp portion of the promoter, which carries two putative c-ets binding sites. We then investigated the effect of glucocorticoids and estradiol by cotransfecting the respective receptors. Both hormones strongly inhibited the stimulation of the LIF promoter by TPA and ionomycin. Since LIF is implicated in the pathogenesis of inflammatory and degenerative conditions, such as rheumatoid arthritis and osteoporosis, the finding that therapeutic agents employed in the treatment of such conditions, i.e. glucocorticoids and estrogens, can modulate the induction of LIF at the transcriptional level, is of particular interest.

Blotting, Southern↗