OBJECTIVE: The aim of this study was to evaluate the use of novel estradiol metered-dose transdermal spray (EMDTS) in the treatment of acute climacteric syndrome. METHODS: A multicenter open-label trial was conducted with a 24-week intervention. EMDTS 1.53 mg was given to symptomatic menopausal women. The Menopause Rating Scale (MRS) was used to assess the climacteric syndrome severity. The Friedman non-parametric test and a post-hoc test with Bonferroni correction were used for statistical evaluation. RESULTS: A total of 132 women were enrolled in 20 centers, of whom 123 (93.2%) completed the study. The average age of patients was 53.8 years (37-65 years). The study was discontinued by 6.8% of women. The patients were checked at the beginning of the study, and after 12 and 24 weeks. There was a statistically significant drop (p < 0.001) in MRS values both after 12 and 24 weeks of therapy. The average MRS values improved by 66.2% between the first and the third visits. The most significant improvement was manifested in patients with initial moderate climacteric syndrome (70.9%). CONCLUSION: This study confirms that application of EMDTS offers a novel treatment option for climacteric symptoms.

• Klíčová slova
• Menopause, climacteric syndrome, estradiol metered-dose transdermal spray, vaginal dryness,
• MeSH
• aplikace kožní MeSH
• dospělí MeSH
• estradiol aplikace a dávkování   MeSH
• estrogenní substituční terapie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• menopauza účinky léků   MeSH
• návaly farmakoterapie   MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• estradiol MeSH

The key mechanisms responsible for achievement of full reproductive and developmental capability in mammals are the differentiation and transformation of granulosa cells (GCs) during folliculogenesis, oogenesis, and oocyte maturation. Although the role of 17 beta-estradiol (E2) in ovarian activity is widely known, its effect on proliferative capacity, gap junction connection (GJC) formation, and GCs-luteal cells transformation requires further research. Therefore, the goal of this study was to assess the real-time proliferative activity of porcine GCs in vitro in relation to connexin (Cx), luteinizing hormone receptor (LHR), follicle stimulating hormone receptor (FSHR), and aromatase (CYP19A1) expression during short-term (168 h) primary culture. The cultured GCs were exposed to acute (at 96 h of culture) and/or prolonged (between 0 and 168 h of culture) administration of 1.8 and 3.6 μM E2. The relative abundance of Cx36, Cx37, Cx40, Cx43, LHR, FSHR, and CYP19A1 mRNA was measured. We conclude that the proliferation capability of GCs in vitro is substantially associated with expression of Cxs, LHR, FSHR, and CYP19A1. Furthermore, the GC-luteal cell transformation in vitro may be significantly accompanied by the proliferative activity of GCs in pigs.

• MeSH
• buněčná diferenciace účinky léků   genetika   MeSH
• estradiol aplikace a dávkování   MeSH
• folikulární buňky účinky léků   metabolismus   MeSH
• IVM techniky MeSH
• lidé MeSH
• oocyty účinky léků   růst a vývoj   MeSH
• oogeneze účinky léků   genetika   MeSH
• prasata MeSH
• proliferace buněk účinky léků   MeSH
• receptory FSH biosyntéza   genetika   MeSH
• receptory LH biosyntéza   genetika   MeSH
• rodina 19 cytochromů P450 biosyntéza   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• estradiol MeSH
• receptory FSH MeSH
• receptory LH MeSH
• rodina 19 cytochromů P450 MeSH

OBJECTIVE: To show possibilities of new application method of estrogen replacement therapy - mettered-dose transdermal spray. DESIGN: Review articleResults: Transdermal spray contains 1.53 mg estradiol in one dose. It gives possibility of individual aproach in estradiol application 1, 2 or 3 doses daily. About 85% of patients showed the significant reduction of hot flushes. Perfect safety profile is predicted especially in cardiovascular point.

• Klíčová slova
• hormone replacement therapy, mettered-dose transdermal spray, perimenopausal symptoms, tromboembolic desease.,
• MeSH
• aerosoly MeSH
• aplikace kožní MeSH
• estradiol aplikace a dávkování   MeSH
• estrogenní substituční terapie metody   MeSH
• klimakterium účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• návaly farmakoterapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• aerosoly MeSH
• estradiol MeSH

PURPOSE: To compare overall survival (OS) for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for advanced breast cancer. PATIENTS AND METHODS: The Fulvestrant First-Line Study Comparing Endocrine Treatments (FIRST) was a phase II, randomized, open-label, multicenter trial. Postmenopausal women with estrogen receptor-positive, locally advanced/metastatic breast cancer who had no previous therapy for advanced disease received either fulvestrant 500 mg (days 0, 14, 28, and every 28 days thereafter) or anastrozole 1 mg (daily). The primary end point (clinical benefit rate [72.5% and 67.0%]) and a follow-up analysis (median time to progression [23.4 months and 13.1 months]) have been reported previously for fulvestrant 500 mg and anastrozole, respectively. Subsequently, the protocol was amended to assess OS by unadjusted log-rank test after approximately 65% of patients had died. Treatment effect on OS across several subgroups was examined. Tolerability was evaluated by adverse event monitoring. RESULTS: In total, 205 patients were randomly assigned (fulvestrant 500 mg, n = 102; anastrozole, n = 103). At data cutoff, 61.8% (fulvestrant 500 mg, n = 63) and 71.8% (anastrozole, n = 74) had died. The hazard ratio (95% CI) for OS with fulvestrant 500 mg versus anastrozole was 0.70 (0.50 to 0.98; P = .04; median OS, 54.1 months v 48.4 months). Treatment effects seemed generally consistent across the subgroups analyzed. No new safety issues were observed. CONCLUSION: There are several limitations of this OS analysis, including that it was not planned in the original protocol but instead was added after time-to-progression results were analyzed, and that not all patients participated in additional OS follow-up. However, the present results suggest fulvestrant 500 mg extends OS versus anastrozole. This finding now awaits prospective confirmation in the larger phase III FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy Naïve Advanced Breast Cancer) trial (ClinicalTrials.gov identifier: NCT01602380).

• MeSH
• anastrozol MeSH
• antagonisté estrogenového receptoru aplikace a dávkování   MeSH
• dospělí MeSH
• estradiol aplikace a dávkování   analogy a deriváty   MeSH
• fulvestrant MeSH
• hormonální protinádorové látky aplikace a dávkování   MeSH
• inhibitory aromatasy aplikace a dávkování   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu farmakoterapie   patologie   MeSH
• nitrily aplikace a dávkování   MeSH
• přežití bez známek nemoci MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• triazoly aplikace a dávkování   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• anastrozol MeSH
• antagonisté estrogenového receptoru MeSH
• estradiol MeSH
• fulvestrant MeSH
• hormonální protinádorové látky MeSH
• inhibitory aromatasy MeSH
• nitrily MeSH
• triazoly MeSH

BACKGROUND: At the time of the initial analysis of overall survival (OS) for the Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) randomized, double-blind, phase III trial, approximately 50% of patients had died. A final analysis of OS was subsequently planned for when 75% of patients had died. METHODS: Patients were randomly assigned 1:1 to fulvestrant 500 mg administered as two 5-mL intramuscular injections on days 0, 14, and 28 and every 28 (±3) days thereafter or fulvestrant 250 mg administered as two 5-mL intramuscular injections (one fulvestrant and one placebo [identical in appearance to study drug]) on days 0, 14 (two placebo injections only), and 28 and every 28 (±3) days thereafter. OS was analyzed using an unadjusted log-rank test. No adjustments were made for multiplicity. Serious adverse events (SAEs) and best response to subsequent therapy were also reported. All statistical tests were two-sided. RESULTS: In total, 736 women (median age = 61.0 years) were randomly assigned to fulvestrant 500 mg (n = 362) or 250 mg (n = 374). At the final survival analysis, 554 of 736 (75.3%) patients had died. Median OS was 26.4 months for fulvestrant 500 mg and 22.3 months for 250 mg (hazard ratio = 0.81; 95% confidence interval = 0.69-0.96; nominal P = .02). There were no clinically important differences in SAE profiles between the treatment groups; no clustering of SAEs could be detected in either treatment group. Type of first subsequent therapy and objective responses to first subsequent therapy were well balanced between the two treatment groups. CONCLUSIONS: In patients with locally advanced or metastatic estrogen receptor-positive breast cancer, fulvestrant 500 mg is associated with a 19% reduction in risk of death and a 4.1-month difference in median OS compared with fulvestrant 250 mg. Fulvestrant 500 mg was well tolerated, and no new safety concerns were identified.

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• estradiol aplikace a dávkování   analogy a deriváty   MeSH
• fulvestrant MeSH
• hormonální protinádorové látky aplikace a dávkování   MeSH
• injekce intramuskulární MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• modulátory estrogenních receptorů aplikace a dávkování   MeSH
• nádory prsu farmakoterapie   metabolismus   mortalita   patologie   MeSH
• odds ratio MeSH
• přežití bez známek nemoci MeSH
• receptory pro estrogeny metabolismus   MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• estradiol MeSH
• fulvestrant MeSH
• hormonální protinádorové látky MeSH
• modulátory estrogenních receptorů MeSH
• receptory pro estrogeny MeSH

The objective is to present an overview of trials and appreciate the relevant data on the effect of steroids pretreatment (oral contraceptives, 17β-estradiol and estradiol valerate) in assisted reproduction cycles. The subject of the study is to evaluate the clinical characteristics during steroids pretreatment cycles focused on the prevention of ovarian cysts, the positive contraceptive effect on the onset of regular period during long gonadotropin releasing hormone agonist protocol. In gonadotropin releasing hormone antagonist protocol the review is interested in supporting ovarian stimulation in low responders, the idea of cycle scheduling and improving treatment outcomes. The method is a review from MEDLINE/Pubmed database between 1994 and July 2012. We identified 15 randomised controlled trials (n=3069 patients). One trail (n=83 patients) assessed GnRH agonist protocol with or without steroids pretreatment, 8 trials (n=1884 patients) assessed GnRH antagonist protocols with or without steroids pretreatment and 6 trials (n=1102 patients) assessed GnRH antagonist protocols versus agonist ones with steroid pretreatment. Data demonstrates that oral contraceptives offer the effective prevention of functional ovarian cysts, the predictable onset of period during desensitisation. Existing data suggest that pretreatment with oral contraceptive pills or estradiol valerate give no advantage concerning number of oocytes or pregnancy rate. Pretreatment with oral contraceptive pills aiming to avoid weekend oocytes retrievals has to be more elucidated. In low responders oral contraceptive pill pretreatment may be beneficial in improving ovarian responses by reducing the amount of gonadotropins and the number of days required for ovarian stimulation. Current research indicates that also 17β-estradiol may be encouraging pretreatment in low responders and in cycle scheduling. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.

• Klíčová slova
• 17β-Estradiol, 2PN, AMH, Assisted reproduction, Estradiol valerate, FSH, GnRH, ICSI, IVF, LH, MII, OHSS, Oral contraceptives, PCOS, RCT, Steroids pretreatment, anti Mullerian hormone, follicle stimulating hormone, gonadotropin releasing hormone, hCG, human chorionic gonadotropin, in vitro fertilisation, intracytoplasmic sperm injection, luteinising hormone, metaphase of the second meiotic division, ovarian hyperstimulation syndrome, polycystic ovary syndrome, randomised controlled trial, two pronucleate stage,
• MeSH
• asistovaná reprodukce * MeSH
• estradiol aplikace a dávkování   analogy a deriváty   MeSH
• hormon uvolňující gonadotropiny agonisté   antagonisté a inhibitory   fyziologie   MeSH
• kontraceptiva orální aplikace a dávkování   MeSH
• lidé MeSH
• ovariální cysty prevence a kontrola   MeSH
• randomizované kontrolované studie jako téma MeSH
• těhotenství MeSH
• úhrn těhotenství na počet žen v reprodukčním věku MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• estradiol MeSH
• hormon uvolňující gonadotropiny MeSH
• kontraceptiva orální MeSH

Estrogens play a crucial role in spermatogenesis and estrogen receptor α knock-out male mice are infertile. It has been demonstrated that estrogens significantly increase the speed of capacitation in vitro; however this may lead to the reduction of reproductive potential due to the decreased ability of these sperm to undergo the acrosome reaction. To date the in vivo effect of estrogens on the ability of sperm to capacitate has not been investigated. Therefore, in this study, we exposed mice (n=24) to 17β-estradiol (E2) at the concentration of 20 ng/ml either during puberty from the fourth to seventh week of age (n=8), or continuously from birth for a period of 12 weeks (n=8) at which age the animals from both groups were killed. The capacitation status of epididymal and testicular sperm was analysed by tyrosine phosphorylation (TyrP) antibody (immunofluorescence and western blot) and chlortetracycline (CTC) assay. According to our results, in vivo exposure to increased E2 concentrations caused premature sperm capacitation in the epididymis. The effect of E2, however, seems reversible because after the termination of the exposure premature epididymal sperm capacitation is decreased in animals treated during puberty. Furthermore the changes in epididymal sperm capacitation status detected by TyrP and CTC positively correlate with plasma levels of E2 and the expression of the estrogen-dependent trefoil factor 1 (Tff1) gene in testicular tissue. Therefore, our data implicate that in vivo exposure to E2 under specific conditions leads to the premature capacitation of mouse sperm in epididymis with a potential negative impact on the sperm reproductive fitness in the female reproductive tract.

• MeSH
• biologické markery metabolismus   MeSH
• časové faktory MeSH
• chlortetracyklin metabolismus   MeSH
• epididymis účinky léků   metabolismus   patologie   MeSH
• estradiol aplikace a dávkování   krev   MeSH
• faktor TFF1 MeSH
• fluorescenční protilátková technika MeSH
• fosforylace MeSH
• kapacitace spermií účinky léků   MeSH
• myši MeSH
• peptidy genetika   metabolismus   MeSH
• rozvrh dávkování léků MeSH
• sexuální vývoj MeSH
• spermie účinky léků   metabolismus   patologie   MeSH
• testis účinky léků   metabolismus   patologie   MeSH
• tyrosin MeSH
• věkové faktory MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• chlortetracyklin MeSH
• estradiol MeSH
• faktor TFF1 MeSH
• peptidy MeSH
• Tff1 protein, mouse MeSH Prohlížeč
• tyrosin MeSH

OBJECTIVE: The objective of this article is to review the recent information about luteal support in the IVF/ET programme. DESIGN: Review article. CONCLUSIONS: The luteal phase support is a necessary part of treatment in stimulated cycles for IVF/ET.

• MeSH
• choriogonadotropin aplikace a dávkování   MeSH
• estradiol aplikace a dávkování   MeSH
• fertilizace in vitro * MeSH
• indukce ovulace * MeSH
• lidé MeSH
• luteální fáze účinky léků   MeSH
• přenos embrya * MeSH
• progesteron aplikace a dávkování   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• choriogonadotropin MeSH
• estradiol MeSH
• progesteron MeSH

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpression increases the aggressiveness of breast cancer cells resulting in poorer prognosis. Patients with HER2-positive disease are less responsive to endocrine therapies. Trastuzumab monotherapy results in objective responses in only approximately 15% of patients. Fulvestrant retains activity in cells overexpressing HER2 that are resistant to other endocrine treatments. This retrospective study evaluated response to fulvestrant treatment among HER2-positive patients with advanced breast cancer (ABC). PATIENTS AND METHODS: Clinical experience data from 10 treatment centres were pooled. Postmenopausal patients with predominantly hormone receptor-positive and HER2-positive disease were included. Clinical benefit (CB) was defined as the proportion of patients achieving a response to treatment (partial or complete) or stable disease lasting >/=6 months. RESULTS: Data for 102 patients were analysed. Fulvestrant resulted in an overall CB rate of 42% (43/101) in HER2-positive patients and 40% (25/63) in patients with visceral disease. Median duration of treatment was 14.5 months (range 6-44 months). Fulvestrant showed activity up to the fourth line of endocrine therapy and up to the seventh line of overall therapy. CONCLUSIONS: Results indicate that fulvestrant may be a suitable treatment option in extensively pre-treated patients with HER2-positive, hormone receptor-positive ABC. Further exploration of its use in this patient population is warranted.

• MeSH
• adjuvantní chemoterapie MeSH
• biologické modely MeSH
• dospělí MeSH
• estradiol aplikace a dávkování   škodlivé účinky   analogy a deriváty   farmakologie   terapeutické užití   MeSH
• fulvestrant MeSH
• hormonální protinádorové látky aplikace a dávkování   škodlivé účinky   farmakologie   terapeutické užití   MeSH
• karcinom farmakoterapie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu farmakoterapie   metabolismus   MeSH
• neoadjuvantní terapie MeSH
• progrese nemoci MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• receptor erbB-2 metabolismus   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• upregulace MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ERBB2 protein, human MeSH Prohlížeč
• estradiol MeSH
• fulvestrant MeSH
• hormonální protinádorové látky MeSH
• receptor erbB-2 MeSH

Ovariectomized mice on a high fat diet represent a model of diet-induced obesity during estrogen deficiency. Here, we tested the hypothesis that sensitivity to centrally administered leptin in ovariectomized mice with diet-induced obesity could be restored by estrogen supplementation. Ovariectomized C57BL/6 female mice were fed either a standard or high fat diet until they were 27 weeks old. Ovariectomized mice on a high fat diet developed extreme obesity and hyperleptinemia and moderate hyperinsulinemia compared to those on a standard diet. For the last 4 weeks, 17beta-estradiol-3-benzoate or its vehicle was administered subcutaneously in a 4-day cyclic regimen. Finally, leptin or saline was injected into the third ventricle, and food intake and body weight were measured for 36 h. In ovariectomized mice fed a standard diet, the decrease in food intake and body weight was significant and was pronounced in 17beta-estradiol-3-benzoate-supplemented mice. The response to centrally injected leptin in ovariectomized mice on a high fat diet was insignificant, whereas in 17beta-estradiol-3-benzoate-supplemented mice, the effect was significant, particularly with respect to body weight. We showed for the first time that central insensitivity to leptin in ovariectomized diet-induced obese mice was restored with 17beta-estradiol-3-benzoate supplementation, which also attenuated most of the parameters of metabolic syndrome. Only circulating adiponectin, a peripheral insulin sensitivity marker, was lowered following 17beta-estradiol-3-benzoate administration in both high fat and standard diet-fed ovariectomized mice, despite of decreased or unchanged glycemia, respectively.

• MeSH
• dieta * MeSH
• dietní tuky aplikace a dávkování   farmakologie   MeSH
• estradiol aplikace a dávkování   farmakologie   MeSH
• hmotnostní přírůstek účinky léků   MeSH
• leptin aplikace a dávkování   farmakologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• obezita metabolismus   MeSH
• ovarektomie * MeSH
• potravní doplňky * MeSH
• stravovací zvyklosti účinky léků   MeSH
• tělesná hmotnost účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dietní tuky MeSH
• estradiol MeSH
• leptin MeSH