Hum Reprod. 2002 Aug;17(8):1997-2002.
Basal serum levels of FSH and estradiol in ovulatory and anovulatory women undergoing treatment by in-vitro maturation of immature oocytes.

Child TJ, Sylvestre C, Pirwany I, Tan SL.

McGill Reproductive Center, Department of Obstetrics and Gynecology, Royal Victoria Hospital, McGill University, Montreal, Quebec, H3A 1A1, Canada. Timothychilahoo.com

BACKGROUND: The study aim was to establish whether basal serum levels of FSH and estradiol are predictive of outcome in women undergoing treatment by in-vitro maturation (IVM) of immature oocytes. METHODS: Data were obtained from 123 unstimulated IVM cycles. Serum was taken between cycle days 2-4 for analysis. Patients received 10 000 IU of HCG 36 h before immature oocyte recovery that was performed between cycle days 9-14. IVM was performed and mature oocytes fertilized by ICSI, followed 2-3 days later by embryo transfer. Outcome measures included the number of immature oocytes retrieved, and the rates of oocyte maturation, fertilization, cleavage and pregnancy. RESULTS: A median (range) of 8 (0-36) immature oocytes was retrieved per patient. Oocyte maturation, fertilization, cleavage and pregnancy rates were 83, 76, 93 and 17.9% respectively. Serum FSH levels and the presence of polycystic ovary were significant independent predictors of the number of immature oocytes retrieved, whilst patient age and basal estradiol level were not. A basal serum estradiol level >100 pmol/l was associated with a significantly higher pregnancy rate (26 versus 11% for estradiol <100 pmol/l; P = 0.032). CONCLUSIONS: Measurement of basal serum levels of FSH and estradiol are useful in predicting the number of immature oocytes retrieved and the pregnancy rate in women undergoing unstimulated IVM treatment.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12151427&dopt=Abstract estradiol




Mol Cell Endocrinol. 2002 Jul 31;193(1-2):29-42.
Adaptive mechanisms induced by long-term estrogen deprivation in breast cancer cells.

Song RX, Santen RJ, Kumar R, Adam L, Jeng MH, Masamura S, Yue W.

Department of Medicine, University of Virginia Health Sciences System, Charlottesville, VA, USA.

Clinical observations suggest that human breast tumors can adapt in response to endocrine therapy by developing hypersensitivity to estradiol. To understand the mechanisms responsible, we examined estrogenic stimulation of cell proliferation in a model system and provided evidence that long-term deprivation of estradiol causes adaptive hypersensitivity. The enhanced responses to estradiol do not involve mechanisms acting at the level of transcription of estrogen regulated genes. We found no evidence of hypersensitivity when examining the effects of estradiol on regulation of c-myc, pS2, progesterone receptor, several ER reporter genes or c-myb in hypersensitive cells. On the other hand, deprivation of breast cells long term was found to up-regulate a separate pathway whereby the estrogen receptor co-opts a classical growth factor pathway and induces rapid non-genomic effects. Through this pathway, estradiol caused rapid activation of mitogen-activated protein (MAP) kinase. In exploring the mechanisms mediating this event, we found that estradiol binds to cell membrane associated estrogen receptors and causes phosphorylation of Shc, an adaptor protein usually involved in growth factor signaling pathways. ERalpha was found to complex with Shc under these conditions. In turn, Shc bound Grb-2 and Sos which resulted in the activation of MAP kinase. The pure antiestrogen, ICI 182,780, blocked several steps in the rapidly responding ER alpha, Shc, MAP kinase pathway. These non-genomic effects of estradiol produced biologic effects by activating Elk and by inducing morphologic changes in cell membranes. Using confocal microscopy, we demonstrated that estradiol caused a rapid alteration in membrane ruffling, the form




Aging Male. 2002 Dec;5(4):233-8.
Association of DHEA-S and estradiol serum levels to symptoms of aging men.

Ponholzer A, Plas E, Schatzl G, Jungwirth A, Madersbacher S; Austrian Society of Urology.

Department of Urology and Andrology and Ludwig Boltzmann Institute for Urological Oncology, Danube Hospital, Langobardenstrasse 122, 1220 Vienna, Austria.

OBJECTIVES: A number of interactions between age-related changes in serum levels of dehydroepiandrostendione sulfate (DHEA-S) and estradiol and symptoms of aging men have been proposed, yet data regarding this issue are scant. We therefore set up a prospective study to analyze these associations. METHODS: In a prospective, cross-sectional study, men aged 45-85 years were recruited. All men completed a questionnaire containing 38 items covering a number of aspects of the aging male. Questionnaires were compiled by using items from previously published and validated questionnaires. Several socioeconomic parameters were also determined. In parallel, serum levels of testosterone, free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), DHEA-S, estradiol, sex hormone binding globulin and prostate-specific antigen (PSA) were quantified by commercially available immunoassays. RESULTS: A total of 375 men with a mean age of 59.9 +/- 9.2 years (mean +/- standard deviation) were analyzed. Average DHEA-S and estradiol levels of 135.8 +/- 90.9 micrograms/dl and 29.7 +/- 14.6 pg/ml, respectively, were recorded. DHEA-S serum levels were negatively correlated to patient age, sexual function score, total score and PSA. Estradiol serum levels were positively correlated to testosterone and free testosterone. None of the other scores or questions revealed a correlation with DHEA-S or estradiol serum levels. CONCLUSION: This prospective study elucidates only small interactions between partial androgen deficiency of the aging male (PADAM)-related symptoms and serum levels of DHEA-S and estradiol. Nevertheless, the data suggest an impac




Maturitas. 2002 Jul 25;42(3):233-42.
Effect of postmenopausal oestradiol and dydrogesterone therapy on lipoproteins and insulin sensitivity, secretion and elimination in hysterectomised women.

Manassiev NA, Godsland IF, Crook D, Proudler AJ, Whitehead MI, Stevenson JC.

Menopause Clinic, King's College Hospital, London, UK.

OBJECTIVES: To investigate in depth the metabolic effects of oestradiol-17 beta both alone and in combination with the progestagen dydrogesterone. METHODS: Fifteen hysterectomised postmenopausal women were studied before treatment and after 24 weeks taking oestradiol-17 beta alone (2 mg per day), then following a further 6 (oestrogen-alone phase) and 12 (oestrogen plus progestagen phase) weeks with inclusion of dydrogesterone (10 mg per day for days 17-28 of each 28 day cycle). Measurements at each visit included fasting serum lipid and lipoprotein concentrations, insulin sensitivity, secretion and elimination by modelling analysis of intravenous glucose tolerance test glucose, insulin and C-peptide concentrations, body fat distribution by dual-energy X-ray absorptiometry (DXA) and arterial function by carotid artery ultrasound. RESULTS: Significant reductions were seen throughout in total and LDL cholesterol. The net reductions in total and LDL cholesterol by the end of the study were 5.8% (P<0.05) and 18.4% (P<0.001), respectively. HDL and HDL subfraction cholesterol concentrations rose during treatment with oestradiol alone, the rise being primarily in the HDL(2) subfraction (+21.6%, P<0.001). Fasting serum triglycerides rose 30% on oestradiol treatment. These increases were unaffected by the addition of dydrogesterone. Insulin sensitivity, secretion and elimination, body fat distribution and arterial function were not significantly affected at any stage of the therapy. CONCLUSIONS: The small study sample and high variability in measures of glucose and insulin metabolism may have contributed to the absence of the expected significant improvement in these pa




BMC Cardiovasc Disord. 2002 Aug 6;2(1):13. Print 2002 Aug 6.
Reduction of post injury neointima formation due to 17beta-estradiol and phytoestrogen treatment is not influenced by the pure synthetic estrogen receptor antagonist ICI 182,780 in vitro.

Finking G, Lenz C, Schochat T, Hanke H.

Institute of Occupational, Social, and Environmental Medicine, University of Ulm, Ulm, Germany. gerald.finkinedizin.uni-ulm.de

BACKGROUND: Animal and organ culture experiments have shown beneficial inhibitory estrogen effects on post injury neointima development. The purpose of this study was to investigate whether such estrogen effects are influenced by the estrogen receptor antagonist ICI 182,780. Different concentrations of 17beta-estradiol and the phytoestrogens genistein and daidzein were tested. METHODS: Female New Zealand White rabbits were benumbed. In situ vascular injury of the thoracic and abdominal aorta was performed by a 3F Fogarty catheter. Segments of 5 mm were randomised and held in culture for 21 days. Three test series were performed: 1) control group--20 microM ICI--30 microM ICI--40 microM ICI. 2) control group--20 microM ICI--40 microM 17beta-estradiol--40 microM 17beta-estradiol + 20 microM ICI. 3) control group--20 microM ICI--40 microM daidzein--40 microM daidzein + 20 microM ICI--20 microM genistein--20 microM genistein + 20 microM ICI. After 21 days the neointima-media-ratio was evaluated. RESULTS: 1) Treatment with ICI 182,780 did not reduce neointima formation significantly (p = 0.05). 2) 40 microM 17beta-estradiol alone (p < 0.0001) and in combination with 20 microM ICI (p < 0.0001) reduced neointima formation significantly. 3) 20 microM genistein alone (p = 0.0083) and combined with 20 microM ICI (p = 0.0053) reduced neointima formation significantly. 40 microM daidzein did not have a significant (p = 0.0637) effect. CONCLUSIONS: The estrogen receptor antagonist ICI 182,780 did not modulate the inhibitory estrogen effects on post injury neointima formation. These results do not support th




Int J Oncol. 2002 Sep;21(3):583-9.
The pattern of estradiol and progesterone differs in serum and tissue of benign and malignant ovarian tumors.

Lindgren PR, Backstrom T, Cajander S, Damber MG, Mahlck CG, Zhu D, Olofsson JI.

Department of Clinical Sciences/Obstetrics and Gynecology, Umea University Hospital, S-901 85 Umea, Sweden. peter.lindgrebgyn.umu.se

Epidemiological studies have indicated a relationship between gonadal steroid hormones and ovarian cancer. A production of both estradiol and progesterone by ovarian cancers has been demonstrated. The local steroid concentrations and the putative relation to histopathological and clinical condition were investigated herein. Ovarian tissue, ovarian tumor cyst fluid, ovarian vein samples and peripheral serum concentrations of estradiol and progesterone in pre- and post-menopausal women, subdivided into groups with normal ovaries, benign, borderline and malignant ovarian tumors, were quantitatively assessed. Both ovarian tissue concentrations of estradiol and progesterone were more than 100-fold higher than in serum. Based on differences in concentrations between different ovarian tumor groups, the data is not coherent with the previously suggested increased production of estradiol and progesterone in ovarian cancer tissue, since post-menopausal women with ovarian cancer presented lower median tissue hormone levels, most pronounced between malignant and benign tumors; median (25 and 75 percentile) estradiol; 9.40 (6.67-15.50) vs 16.44 (12.49-23.20), p=0.02 and progesterone; 308 (240-575) vs 957 (553-1143) pmol/g wet weight, p<0.01, n=81. Lower concentrations of estradiol, but not progesterone, were found in ovarian cancer tissue, ovarian cyst fluid and peripheral serum in patients with FIGO stages 3 and 4 than in stages 1 and 2. The novel finding of a large ovarian tissue to serum difference of both estradiol and progesterone indicates an important role of ovarian tissue concentrations in tumor biology and raises the question of ad




J Assist Reprod Genet. 2002 Jul;19(7):349-53.
Day 6 estradiol level predicts cycle cancellation among poor responder patients undergoing in vitro fertilization-embryo transfer cycles using a gonadotropin-releasing hormone agonist flare regimen.

Kovacs P, Witt BR.

Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. pkovcol.com

PURPOSE: To compare two GnRHa flare protocols among poor responders undergoing IVF-ET and to evaluate if a Day 6 estradiol level can predict outcome. METHODS: Retrospective analyses of GnRHa flare IVF cycles among poor responders. Group A ("miniflare," N = 36) 40 microg GnRHa s.c. b.i.d. from Day 3; Group B ("standard flare," N = 24) 1 mg GnRHa on Days 2-3; 0.5 mg GnRHa from Day 4. ROC analysis was performed to find a Day 6 estradiol value that is predictive of cycle outcome. RESULTS: With the standard flare, patients required less gonadotropins and tended to have fewer cancellations and higher pregnancy rates. A Day 6 estradiol level < or = 75 pg/mL was predictive of cycle cancellation, but not of pregnancy outcome. CONCLUSIONS: Standard GnRHa flare offers some advantages over the miniflare. Day 6 estradiol < or = 75 pg/mL is predictive of cycle cancellation. When the estradiol level is low on Day 6 (no flare), early cancellation should be considered.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12168736&dopt=Abstract estradiol




Biosci Rep. 2001 Oct;21(5):637-52.
17beta-estradiol enhances the flux of cholesterol through the cholesteryl ester cycle in human macrophages.

Napolitano M, Blotta I, Montali A, Bravo E.

Laboratory of Metabolism and Pathological Biochemistry, Istituto Superiore di Sanita, Rome, Italy.

Estrogens have been shown to have many positive effects on the function of arterial wall, and recent evidence suggest that 17beta-estradiol has a direct action in reducing the accumulation of cholesteryl ester in macrophages. The mechanisms underlying the effects of 17beta-estradiol on foam cell formation, however are poorly understood. The aim of this study is to investigate the role of 17beta-estradiol in the regulation of the cholesteryl ester cycle and cholesterol efflux in human macrophages. In addition, the influence of 17beta-estradiol on apolipoprotein E (apoE) and lipoprotein lipase (LDL) secretion by the cells was also tested. Human Monocyte Derived Macrophages (HMDM), matured in the presence or the absence of 17beta-estradiol, were loaded with [3H]-cholesteryl ester-labeled-acetyl LDL (low density lipoprotein) and the efflux of radioactivity into the medium was measured. The effect of 17beta-estradiol on cellular activities of acyl coenzyme A: cholesterol acyl transferase (ACAT), and both neutral and acid cholesteryl ester hydrolase (CEH) and the secretion of apoE and LDL into the medium, were also studied. The results indicate that 17beta-estradiol induces an increase in the amount of labeled cholesterol released from the cells and, the data obtained from the measurements of ACAT and CEH activities showed that, in estrogen-treated HMDM, the cholesteryl ester cycle favors the hydrolysis of lipoprotein cholesterol by CEH in comparison with its acylation by ACAT. In particular, for the first time a strong enhancement of neutral and acid CEH in human macrophages by 17beta-estradiol, was demonstrated. ApoE and LDL secretion increased during the maturation of monocytes to macrophages, and was not mo




Anticancer Res. 2002 Jul-Aug;22(4):2051-60.
Effects of PC-SPES on proliferation and expression of AR/PSA in androgen-responsive LNCaP cells are independent of estradiol.

Hsieh TC, Xiong W, Traganos F, Darzynkiewicz Z, Wu JM.

Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595, USA.

Previous studies have suggested that the clinical efficacy of PC-SPES, a dietary supplement used frequently by men diagnosed with androgen-dependent (AD) or androgen-independent (AI) prostate cancer (CaP), is mechanistically attributed to estrogenic components present in the herbal mixture. To test this hypothesis, we compared estradiol (1 nM), potentially an active principle in PC-SPES, with PC-SPES (using an amount equivalent to 1 nM estradiol) on cell proliferation, induction of apoptosis, and regulation of prostate specific genes, PSA and AR, in androgen-responsive LNCaP cells. Cells cultured in steroid-proficient (FBS) or-deficient (CS-FBS) media to simulate hormonal status pre- and post-castration in vivo, were incubated with estradiol or PC-SPES. Proliferation was reduced in PC-SPES treated cells cultured in media supplemented with FBS or CS-FBS; in contrast, addition of estradiol had no effect on proliferation in FBS cultures, and elicited a 45% growth increase in CS-PBS-supplemented cultures. The differential proliferative response of LNCaP cells to PC-SPES vs. estradiol was also supported by changes in PCNA expression, cell viability, cell cycle phase distribution, and induction of apoptosis. Estradiol elicited time-dependent increases in secreted PSA, whereas PC-SPES suppressed PSA secretion, in both culture conditions. In FBS cultures, PC-SPES lowered intracellular AR and PSA by 61% and 17%, respectively, while estradiol increased intracellular PSA, in parallel with a 42% decrease in AR expression. In comparison with cells maintained with CS-FBS, estradiol induced substantial increases in both intracellular PSA and AR, whereas PC-SPES resulted in a smaller increase i