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Hormonal Treatment (hormonal + treatment)
Selected AbstractsNew and emerging treatments in dermatology: acneDERMATOLOGIC THERAPY, Issue 2 2008A. Katsambas ABSTRACT:, Topical retinoids, benzoyl peroxide, azelaic acid, and topical and oral antibiotics remain the milestone of treatment for mild to moderate acne vulgaris. Oral isotretinoin is useful for the treatment of severe nodular acne, treatment-resistant acne, and acne with a risk of physical or psychological scarring. Hormonal treatment in female acne is useful in resistant or late-onset acne. With increasing concerns regarding teratogenicity of isotretinoin and increasing antibiotic resistance, there is a clear need for therapeutic alternatives to these long-used treatments. Research in the pathogenesis of acne has allowed for new therapies and future perspectives regarding acne to evolve. They include low-dose long-term isotretinoin regimens, insulin-sensitizing agents, 5,-reductase type 1 inhibitors, topical photodynamic therapy, new combination formulations, dietary interventions, and antiinflammatory agents such as lipoxygenase inhibitors. [source] Expression of Pit2 sodium-phosphate cotransporter during murine odontogenesis is developmentally regulatedEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 6 2006Dawei Zhao Different sodium-dependent inorganic phosphate (Pi) uptake mechanisms play a major role in cellular Pi homeostasis. The function and detailed distribution patterns of the type III Na+ -phosphate cotransporter, PiT-2, in different organs during development are still largely unknown. We therefore examined the temporospatial expression patterns of Pit2 during murine odontogenesis. Odontoblasts were always devoid of Pit2 expression, whereas a transient, but strong, expression was detected in young secretory ameloblasts. However, the stratum intermedium and, later on, the papillary layer and cells of the subodontoblastic layer, exhibited high levels of Pit2 mRNA, which increased gradually as the tooth matured. Hormonal treatment or Pi starvation of tooth germs in vitro did not alter Pit2 levels or patterns of expression, indicating mechanisms of regulation different from those of PiT-1 or other cell types. PiT-2 also functions as a retroviral receptor, and functional membrane-localized protein was confirmed throughout the dental papilla/pulp by demonstrating cellular permissiveness to infection by a gammaretrovirus that uses PiT-2 as a receptor. The distinct pattern of Pit2 expression during odontogenesis suggests that its Pi -transporter function may be important for homeostasis of dental cells and not specifically for mineralization of the dental extracellular matrices. The expression of viral receptors in enamel-forming cells and the dental pulp may be of pathological significance. [source] Intracytoplasmic sperm injection as a complement to gonadotrophin treatment in infertile men with hypogonadotrophic hypogonadismINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 4 2005BRANKO ZORN Summary In this study we sought to determine whether intracytoplasmic sperm injection (ICSI) could improve the efficacy of treatment with gonadotrophins in gonadotrophin-deficient men in terms of pregnancy. A series of six adult men (aged 26,47 years) with hypogonadotrophic hypogonadism (HH) is reported: four men with prepubertal isolated idiopathic HH (IIHH) and two adult-onset HH, as part of hypopituitarism secondary to surgical treatment of a pituitary tumour. All were azoospermic. To restore spermatogenesis, all received hormonal treatment with intramuscular human menopausal gonadotrophins (HMG) and human chorionic gonadotrophin (HCG) for 2 to 23 months. High basal serum inhibin B was predictive of rapid and complete recovery of spermatogenesis. In the two adult-onset HH, a natural pregnancy was achieved within 3 months. The four men with IIHH underwent ICSI because of poor sperm quality. ICSI using fresh or frozen-thawed ejaculated spermatozoa was performed after 6,23 months of gonadotrophin treatment. ICSI provided good clinical results in terms of fertilization and embryo quality, and resulted in three pregnancies that ended in three term deliveries. In men with oligozoospermia related to prepubertal IIHH, ICSI shortens the hormonal treatment and enhances the chances of pregnancy. [source] Suppression of testosterone stimulates recovery of spermatogenesis after cancer treatmentINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2003Marvin L. Meistrich Summary It is important to develop methods to prevent or reverse the infertility caused by chemotherapy or radiation therapy for cancer in men. Radiation and some chemotherapeutic agents kill spermatogonial stem cells, but we have shown that these cells survive in rats, although they are unable to differentiate. There is evidence that this phenomenon also occurs in men. The block to spermatogonial differentiation in rats is caused by some unknown change, either in the spermatogonia or the somatic elements of the testis, such that testosterone inhibits spermatogonial differentiation. In the rat, the spermatogenesis and fertility lost following treatment with radiation or some chemotherapeutic agents can be restored by suppressing testosterone with gonadotropin releasing hormone (GnRH) agonists or antagonists, either before or after the cytotoxic insult. The applicability of this procedure to humans is still unknown. Some anticancer regimens may kill all the stem cells, in which case the only option would be spermatogonial transplantation. However, in some cases stem cells survive and there is one report of stimulation of recovery of spermatogenesis with hormonal treatment. Clinical trials should focus on treating patients with hormones during or soon after anticancer treatment. The hormone regimen should involve suppression of testosterone production with minimum androgen supplementation used to improve the diminished libido. [source] Peroxisome proliferator-activated receptor delta expression and regulation in mouse uterus during embryo implantation and decidualizationMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2003Nai-Zheng Ding Abstract The aim of this study was to examine the expression and regulation of peroxisome proliferator-activated receptor (PPAR) PPAR, gene in mouse uterus during early pregnancy by in situ hybridization and immunohistochemistry. PPAR, expression under pseudopregnancy, delayed implantation, hormonal treatment, and artificial decidualization was also investigated. There was a very low level of PPAR, expression on days 1,4 of pregnancy. On day 5 when embryo implanted, PPAR, expression was exclusively observed in the subluminal stroma surrounding the implanting blastocyst. No corresponding signals were seen in the uterus on day 5 of pregnancy. There was no detectable PPAR, signal under delayed implantation. Once delayed implantation was terminated by estrogen treatment and embryo implanted, a strong level of PPAR, expression was induced in the subluminal stroma surrounding the implanting blastocyst. Estrogen treatment induced a moderate level of PPAR, expression in the glandular epithelium, while progesterone treatment had no effects in the ovariectomized mice. A strong level of PPAR, expression was seen in the decidua on days 6,8 of pregnancy. PPAR, expression was also induced under artificial decidualization. These data suggest that PPAR, expression at implantation sites require the presence of an active blastocyst and may play an essential role for blastocyst implantation. Mol. Reprod. Dev. 66: 218,224, 2003. © 2003 Wiley-Liss, Inc. [source] Epigenetic chromatin modifiers in barley: I. Cloning, mapping and expression analysis of the plant specific HD2 family of histone deacetylases from barley, during seed development and after hormonal treatmentPHYSIOLOGIA PLANTARUM, Issue 3 2009Kyproula Demetriou Epigenetic phenomena have been associated with modifications of chromatin structure. These are achieved, in part, by histone post-translational modifications including acetylations and deacetylations, the later being catalyzed by histone deacetylaces (HDACs). Eukaryotic HDACs are grouped into three major families, RPD3/HDA1, SIR2 and the plant-specific HD2. HDAC genes have been analyzed from model plants such as Arabidopsis, rice and maize and have been shown to be involved in various cellular processes including seed development, vegetative and reproductive growth and responses to abiotic and biotic stress, but reports on HDACs from other crops are limited. In this work two full-length cDNAs (HvHDAC2-1 and HvHDAC2-2) encoding two members of the plant-specific HD2 family, respectively, were isolated and characterized from barley (Hordeum vulgare), an agronomically important cereal crop. HvHDAC2-1 and HvHDAC2-2 were mapped on barley chromosomes 1H and 3H, respectively, which could prove useful in developing markers for marker-assisted selection in breeding programs. Expression analysis of the barley HD2 genes demonstrated that they are expressed in all tissues and seed developmental stages examined. Significant differences were observed among tissues and seed stages, and between cultivars with varying seed size, suggesting an association of these genes with seed development. Furthermore, the HD2 genes from barley were found to respond to treatments with plant stress-related hormones such as jasmonic acid (JA), abscisic acid (ABA) and salicylic acid (SA) implying an association of these genes with plant resistance to biotic and abiotic stress. The expression pattern of HD2 genes suggests a possible role for these genes in the epigenetic regulation of seed development and stress response. [source] Second Oestrus Synchronization and Precocious Embryo Viability after Puberty Induction in Gilts by the Use of Gonadotrophin TreatmentREPRODUCTION IN DOMESTIC ANIMALS, Issue 2 2005V Do Lago Contents The use of exogenous gonadotrophins in puberty inducement and ovulation synchronization is a technique that has a positive influence on the management of swine. The purpose of this study was to verify the effects of a second gonadotrophin treatment [equine chorionic gonadotrophin (eCG) and luteinizing hormone (LH), intramuscularly (i.m.)] upon the second oestrus synchronization and fertility in gilts. Seventy-one NAIMAź (Pen Ar Lan) gilts had their first oestrus (puberty inducement) induced by a hormonal treatment (eCG and LH). Then, they were randomly distributed into two treatments, with (T1) and without (C) gonadotrophin treatment at the second oestrus. The animals were fed with a single ration (16% of crude protein and 3286.73 kcal ME/kg), and timed artificial insemination performed at the second oestrus. Gilts were slaughtered for embryo recovery and ovary examination about 5 days after insemination. There was no evidence of a difference in the percentage of the second oestrus expression (T1 , 90.90% and C , 86.84%), the duration of the oestrus cycle (T1 , 19.62 ± 0.82 days and C , 19.67 ± 4.14 days), the percentage of follicular cysts (T1 , 15.15% and C , 18.42%) and number of ovulations (T1 , 14.60 ± 5.7 and C , 13.23 ± 4.8) between treatments (p > 0.05). However, the hormonal treatment (T1) showed minor oestrus dispersion and embryo viability (T1 , 8.4 ± 5.6 and C , 11.2 ± 4.6) (p < 0.05). These results indicate that the better synchronization and expression of the second oestrus when using gonadotrophins (eCG and LH) is followed by a lower embryo viability, which is probably the consequence of the heterogeneous follicle recruitment during the injection of eCG. [source] Ovum Pick-up in Cycling and Lactating Postpartum Swamp Buffaloes (Bubalis bubalis)REPRODUCTION IN DOMESTIC ANIMALS, Issue 2 2005A Promdireg Contents The objective of this study was to evaluate the efficiency of Ovum Pick Up (OPU) in cycling (n = 5) and lactating, postpartum, swamp buffaloes (n = 6) with and without gonadotropin stimulation. The OPU was performed every two weeks in all groups of animals, for a total of six sessions. Thirty collections were performed in five cycling buffaloes and 36 collections in six lactating postpartum buffaloes. Buffaloes that received hormonal stimulation were given a total of 400 mg, follicle stimulating hormone (FSH), administered twice daily over 3 days in decreasing doses, together with 100 ,g of GnRH, 24 h after the last FSH injection. Following a resting period of 1 month, the two groups of buffaloes, were subjected to the same OPU regimen, but without any hormonal treatment for an additional six OPU sessions. The number of aspirated follicles recorded from the hormonal stimulated, cycling animals and lactating, postpartum buffaloes was not significantly different, 7.2 ± 3.7 and 9.0 ± 3.2, respectively (p > 0.05). Recovered oocytes collected from the two groups of hormonally stimulated animals were also not statistically different: 3.7 ± 2.7 in the cycling and 5.9 ± 3.5 in the lactating postpartum group (p > 0.05). In the two groups of buffaloes not receiving hormonal stimulation, the number of aspirated follicles was not significantly different: 2.1 ± 1.4 and 1.4 ± 0.7 in cycling and lactating postpartum buffaloes respectively (p > 0.05). Recovered oocytes in the non-treated groups were also similar: 1.4 ± 1.3 vs 0.7 ± 0.8 in cycling and lactating buffaloes (p > 0.05). Among stimulated buffaloes, most aspirated follicles were small in size (,5 mm), whereas they were mostly medium and large sizes in the non-treated buffaloes. The oocyte recovery rate in both the groups, cycling and lactating postpartum, were 51.6% and 69.5% in stimulated groups and 55.0% and 53.1% in non-stimulated groups (p > 0.05). The majority of recovered oocytes were single- and multi-layered, and the number was greater in the cycling than in the lactating, postpartum buffaloes. The number and quality of recovered oocytes was similar in all groups of buffaloes whether they were received or did not receive hormonal stimulation. Moreover no difference was found in multi- and single-layered oocytes between cycling and lactating, postpartum buffaloes. In conclusion, OPU can be performed successfully in swamp buffalo in different reproductive status and FSH administration was shown to increase the number of aspirated oocytes in both cycling and lactating, postpartum buffaloes. [source] Effect of Long-Term Testosterone Administration on the Endometrium of Female-to-Male (FtM) TranssexualsTHE JOURNAL OF SEXUAL MEDICINE, Issue 11 2009Anna Myriam Perrone MD ABSTRACT Introduction., Long term safety of testosterone (T) administration in women is still unknown. In particular few and discordant data exists on the effects of T on the endometrium. Aim., The aim of this study was to investigate the effects of long-term T treatment on endometrium histology and proliferation in female to male transsexual subjects (FtM). We compared these endometria with those of young women in the proliferative phase (PM) of the cycle and with those of post menopausal women (M). Method., Endometrial samples from 27 FtM treated with T (intramuscular injection of 100 mg Testoviron Depot /10 days for at least one year), 30 M undergoing vaginal hysterectomy, and 13 PM undergoing hysteroscopy for infertility problems were collected. Endometrial proliferation was evaluated on the basis of histopathology and expression of the proliferation marker Ki-67. Both M and PM women had not received any hormonal treatment for at least one year. Main Outcome Measure., Circulating total testosterone (TT), estradiol (E), progesterone (P), insulin and glucose levels were measured in FtM and PM subjects. Results., FtM had received T for 33.6 ± 21.3 months (mean ± SD). In FtM subjects, histological analysis found inactive endometrium similar to the atrophic menopausal endometrium. The expression of Ki-67 in the glands, stroma and glands and stroma together was significantly (p < 0.0005) lower in FtM than in PM women and was similar in the FtM and M groups. Small polyps were detected in 5 of the 27 FtM subjects. Conclusions., In conclusion our data suggest that exogenous T administration does not stimulate endometrial proliferation in FtM transsexuals and indeed may have atrophic effects. Perrone AM, Cerpolini S, Salfi NCM, Ceccarelli C, Badiali De Giorgi L, Formelli G, Casadio P, Ghi T, Pelusi G, Pelusi C, and Meriggiola MC. Effect of long-term testosterone administration on the endometrium of female-to-male (FtM) transsexuals. J Sex Med 2009;6:3193,3200. [source] Significance of preoperative HbA1c level in patients with diabetes mellitus and clinically localized prostate cancer,THE PROSTATE, Issue 8 2009Sung Kyu Hong Abstract INTRODUCTION We investigated potential relationships of history of diabetes mellitus (DM) and glycemic control, represented by hemoglobin A1c (HbA1c) level, with characteristics of tumor among patients who received radical prostatectomy (RP) for clinically localized prostate cancer. METHODS We reviewed data of 740 patients who underwent RP for clinically localized prostate cancer between 2004 and 2008 without receiving preoperative radiation or hormonal treatment. Univariate and multivariate logistic regression analyses addressed the associations of history of DM and HbA1c level with known prognostic variables of prostate cancer. RESULTS No significant differences were observed in various preoperative and pathological parameters between those with (n,=,89) and without DM (n,=,651). When only the subjects with DM were divided into two groups (group 1 and 2) according to HbA1c level (<6.5% vs. ,6.5%), group 2 demonstrated significantly higher rate of extraprostatic extension of tumor (P,=,0.043) and high (,7) pathological Gleason score (P,=,0.005) than group 1. Also among those with DM, HbA1c level was observed to be an independent predictor for high pathologic Gleason score (P,=,0.010) and extraprostatic extension of tumor (P,=,0.035), respectively in multivariate analyses. CONCLUSION Although simple history of having DM may not be a significant factor regarding aggressiveness of clinically localized prostate cancer, the glycemic control, as represented by HbA1c level, may be a useful preoperative predictor of aggressive tumor profile among patients with DM who are also diagnosed with clinically localized prostate cancer. Prostate 69: 820,826, 2009. © 2009 Wiley-Liss, Inc. [source] Regulation of urogenital smooth muscle patterning by testosterone and estrogen during prostatic inductionTHE PROSTATE, Issue 7 2006Holly Chrisman Abstract Background Smooth muscle (SM) has been proposed to play an important role in controlling prostate organogenesis by regulating signaling between inductive mesenchyme and developing epithelial prostatic buds. Methods We have examined the effects of testosterone and estrogen upon SM patterning in the embryonic rat urogenital tract (UGT) using in vitro organ cultures, immunohistochemistry, and Western blotting. Results We observed that testosterone elicited a sexually dimorphic difference in SM structure of embryonic UGTs, in cultures grown with testosterone. The addition of estrogen led to an increase in the rate of SM closure, in both males and females. To quantify the effects of steroids upon SM we used Western blotting of SM actin, which showed that estrogen stimulated SM content, while testosterone reduced SM content. Finally, we examined the expression of ER,, ER,, PR, and SM actin under different hormonal treatments of UGTs grown in vitro. The expression patterns of ER, and ER, were largely unchanged by hormonal treatment, while PR showed a much broader expression pattern in response to estradiol. Conclusions Our results indicate that testosterone can directly regulate SM patterning and content in the UGT, and that SM is sensitive to both androgens and estrogens. © 2006 Wiley-Liss, Inc. [source] Elevated serum progastrin-releasing peptide (31,98) in metastatic and androgen-independent prostate cancer patients,THE PROSTATE, Issue 2 2002Masahiro Yashi Abstract BACKGROUND Increases in neuroendocrine phenotype and secretory products are closely correlated with tumor progression and androgen independence in prostate cancer. In this study, we explored this correlation using serum progastrin-releasing peptide (ProGRP), a carboxy-terminal region common to three subtypes of precursors for gastrin-releasing peptide (GRP), which is released from the neuroendocrine phenotype to act as a growth factor. METHODS In 60 patients with benign prostatic hyperplasia (BPH) and 200 with prostate cancer, serum ProGRP levels were determined with an enzyme-linked immunosorbent assay (ELISA) kit and evaluated in relation to clinical stage, hormonal treatment, and prostate-specific antigen (PSA) values. Fourteen randomly selected patients were entered in the follow-up study. Additionally, expression of ProGRP as determined by immunohistochemical analysis was compared to that of chromogranin-A (CgA) in tissue samples from several subjects. RESULTS We found a positive correlation between PSA and ProGRP in patients with untreated prostate cancer; no correlation was found in the treated groups. The increases in the ProGRP value and in the percentage of patients with higher than normal values were significant (P,<,0.0001), especially in the androgen-independent group (P,<,0.0001). A longitudinal study showed that, in a subset of patients, the ProGRP values tended to increase transiently when the cancer became androgen independent, but remained unchanged or decreased at the androgen-dependent stage. Positive staining for ProGRP occurred in a different distribution in neuroendocrine tissues than that of staining for CgA. CONCLUSIONS The clinical results demonstrated the existence of a regulatory mechanism for GRP, which to date had only been observed in cell lines. These findings suggest that GRP is a growth factor potentially upregulated by androgen but that does not rely principally on androgen modulation. The large overlap in levels of ProGRP among the groups limits the use of this value as a monitoring tool. Measurement of ProGRP, however, does have potential as an independent parameter to evaluate androgen-independent progression and to facilitate a new therapeutic strategy that may compensate for current limitations of diagnosis based on PSA alone. Prostate 51: 84,97, 2002. © 2002 Wiley-Liss, Inc. [source] CHARGE syndrome as unusual cause of hypogonadism: endocrine and molecular evaluationANDROLOGIA, Issue 5 2010L. Foppiani Summary Coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies (CHARGE) syndrome is a genetic syndrome in which hypogonadism is a frequent feature. A causative mutation within the chromodomain helicase DNA-binding protein-7 gene, which plays an important role in the embryonic development, is present in 2/3 of affected patients. We describe the clinical, hormonal and molecular characteristics of a young man from Ecuador who was diagnosed as having CHARGE syndrome at an adult age. The patient showed several phenotypic features of the syndrome, associated with a prepubertal state and cryptorchidism; hypogonadotrophic hypogonadism with undetectable testosterone levels not responsive to hCG testing and severe osteoporosis were ascertained. Molecular evaluation of the CHD7 gene showed the novel frameshift truncating heterozygous mutation p.Tyr1046Glyfs*23 in exon 12. Magnetic resonance imaging revealed mild hypoplasia of the pituitary gland and hypoplasia of the posterior cranial fossa. Parenteral testosterone therapy led to sexual development over time and, in combination with diphophonate therapy and calcium,vitamin D supplementation, significantly improved bone mineralisation. Early proper hormonal treatment of hypogonadism in patients with complex genetic syndromes is important to achieve normal sexual maturation, improve quality of life and avoid significant comorbidities, such as osteoporosis. [source] Increase in milt production by hormonal treatment in the pejerrey fish Odontesthes bonariensis (Valenciennes 1835)AQUACULTURE RESEARCH, Issue 15 2005Leandro A Miranda Abstract In spite of interest in the cultivation of the pejerrey fish Odontesthes bonariensis (Cuvier & Valenciennes 1835), there are few studies on subjects required to advance this activity. One of the problems is the synchronization of female and male maturation to provide eggs and sperm for larval production. The low volume of expressible milt, either in wild or culture fish, is a major problem. The aim of this work was to study the effectiveness of the administration of different hormones on sperm production in pejerrey. Milt production was enhanced by the injection of human chorionic gonadotropin (hCG) (16.7-fold increase, 625 IU kg,1), carp pituitary extracts (13.5-fold increase, 30 mg kg,1), salmon pituitary extracts (12.8-fold increase, 30 mg kg,1), salmon-type gonadotropin-releasing hormone analogue (GnRH) (16.7-fold increase, 10 ,g kg,1) and mammalian-type GnRH analogue (10.8-fold increase, 20 ,g kg,1). Sperm concentration, motility and the fertilization rate were not statistically different compared with control groups. It was also demonstrated that sperm could be obtained off-season. Taken together, hCG is recommended to stimulate pejerrey spermiation because it is effective in low doses is inexpensive and is widely available. [source] Chronic cystic ovarian disease in a Holstein cowAUSTRALIAN VETERINARY JOURNAL, Issue 1-2 2005AM PADULA Cystic ovarian follicles are commonly found during rectal examination of early postpartum dairy cows, usually presenting with anoestrus and occasionally nymphomania. Most cases self cure with time, or respond to exogenous hormonal treatment. This case report describes a refractory case in a Holstein cow in which a novel treatment approach was used. A gonadotrophin releasing hormone agonist implant was inserted for 180 d in an attempt to suppress pituitary gonadotrophin output, arrest abnormal ovarian follicle growth and prevent steroidogenesis. Frequent serial blood samples were collected before and after implant insertion to monitor changes in pulse release of luteinising hormone. Follow up ultrasound scans and blood samples were done to monitor ovarian structures; progesterone and oestradiol were collected at various times over the 180 d period. A normal, cycling herdmate was enrolled as a control. Prior to implant insertion, high frequency and low amplitude luteinising hormone pulses were detected in the cystic cow. Insertion was followed by a sustained surge in the release of luteinising hormone in both cows, but ovulation was not induced in the cystic cow. Plasma oestradiol levels remained consistently elevated and signs of oestrous behaviour were observed. Long term gonadotrophin releasing hormone agonist treatment failed to suppress either ovarian steroid production or cause regression of the cysts by 180 d. [source] Effect of age and single versus multiple dose pharmacokinetics of letrozole (Femaraź) in breast cancer patientsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5 2001Christian U. Pfister Abstract Letrozole (trademark Femaraź) is a new orally active, potent and selective aromatase inhibitor for the hormonal treatment of advanced breast cancer in postmenopausal women. The pharmacokinetics of letrozole and the suppression of peripheral estrogens were studied in 28 breast cancer patients after a single dose and at steady state. The pharmacokinetics of two distinct age groups (,50, ,65, N=15 and ,70 years old, N=9) were compared. There were no significant differences in area under the curve (AUC) or terminal half-life between the two age groups neither after a single dose nor at steady state. However, when comparing steady state to single dose kinetics, half-life and AUC increased significantly by 42% (90% CI: 1.13, 1.78) and 28% (90% CI: 1.12, 1.47), respectively. This deviation from linearity was probably due to a partial saturation or auto-inhibition of the dominant metabolic clearance mechanism of letrozole. At steady state, approximately 70% of the administered dose was excreted in urine as unchanged letrozole (6.0±3.8%) or as the glucuronide of the major, pharmacologically inactive metabolite CGP44645 (64.2±22.7%). A single dose of letrozole caused suppression of serum estrogen levels close to the quantification limit of the assay. No difference between single dose suppression and suppression at steady state could be detected. Copyright © 2001 John Wiley & Sons, Ltd. [source] Efficacy of low-dose dexamethasone in castration-refractory prostate cancerBJU INTERNATIONAL, Issue 4 2008Ramachandran Venkitaraman OBJECTIVE To evaluate the prostate-specific antigen (PSA) response rate and duration of PSA response to dexamethasone in patients with castration-refractory prostate cancer (CRPC), as corticosteroids are frequently used as second-line hormonal treatment of CRPC and there is little published evidence concerning the efficacy of low-dose dexamethasone in this setting. PATIENTS AND METHODS In all, 102 patients with progressive CRPC received oral dexamethasone (0.5 mg daily) between January 2003 and October 2006. The median pretreatment PSA level was 83 ng/mL. The main endpoint was the PSA response rate according to the PSA Working Group criteria. RESULTS In all, 50 patients (49%) had a confirmed PSA response. The median (range) time to PSA progression for the entire cohort was 7.4 (1,28) months. In responders, the median duration of the PSA response was 11.6 (1,24) months. CONCLUSION Low-dose dexamethasone has significant activity in CRPC. Subject to validation with more clinically meaningful endpoints, dexamethasone could become the corticosteroid of choice in the management of CRPC, and its potential for use in combination with novel agents should be explored. [source] Relationship between adult dark spermatogonia and secretory capacity of Leydig cells in cryptorchidismBJU INTERNATIONAL, Issue 5 2007Dragana Zivkovic In a paper from Switzerland, the authors describe the relationship between adult dark spermatogonia and the secretory capacity of Leydig cells in cryptorchidism. OBJECTIVE To examine whether hormonal therapy before orchidopexy affects the histology of the testis and to assess the responsiveness of the Leydig cells, as it has been shown that although basal plasma testosterone levels are within the ,normal' range in cryptorchid boys there is an insufficient increase of testosterone after a human chorionic gonadotrophin (hCG) stimulation in ,,30% of cryptorchid boys. PATIENTS AND METHODS In all, 55 boys (aged 1,7 years) with a unilateral undescended testis were included in the study and divided into two groups. Group I (32 boys) received hormonal therapy before orchidopexy; 17 boys received a long-acting LHRH analogue (buserelin) administered as a nasal spray in doses of 20 ”g/day for 28 days, followed by 1500 IU hCG intramuscularly (i.m.) once a week for 3 weeks, and the remaining 15 received 1500 IU hCG i.m. once a week for 3 weeks. Group II (33 boys) had orchidopexy alone. During orchidopexy biopsies were taken from the undescended and contralateral descended testes of the boys in both groups for histological analyses. Variations in the number of adult dark (Ad) spermatogonia per tubule (Ad/T) were assessed and testosterone levels were measured during the course of the hormonal therapy (before treatment, 14 days after initiation of buserelin administration, 24 h after each hCG injection, and 3 months after cessation of therapy). RESULTS In group I, 17 boys (53%) had a ,normal' Ad/T after hormonal treatment vs only six (18%) in group II after orchidopexy alone (P = 0.019). In the hormonally treated boys (group I) we compared the testosterone values 24 h after the second injection of hCG (when the response was most pronounced). Those with a normal Ad/T had a mean (sd) testosterone level of 199.5 (97.6) ng/dL vs 99.6 (85) ng/dL in those with an inadequate Ad/T response to hormonal therapy (P < 0.003). CONCLUSION We have confirmed that there are two subgroups of cryptorchid boys. Patients with a sufficient Leydig cell secretory capacity will have normal testicular histology and Ad spermatogonia count after hormonal treatment. While those with a suboptimal Leydig cell capacity will have a low Ad spermatogonia count and consequently poor prognosis for future fertility, despite successful surgery. As to whether different types and durations of the hormonal therapy in patients with impaired Leydig cell response could lead to improved testicular histology and consequently improved prognosis for future fertility, remains to be answered. [source] Systematic review of early vs deferred hormonal treatment of locally advanced prostate cancer: a meta-analysis of randomized controlled trialsBJU INTERNATIONAL, Issue 6 2007Gregory Boustead OBJECTIVE To compare the effectiveness of hormonal treatment (luteinizing hormone-releasing hormone agonists and/or antiandrogens) as an early or as a deferred intervention for patients with locally advanced prostate cancer (LAPC), as radiotherapy is currently the standard treatment for LAPC, with hormonal treatment considered a reserve option. METHODS We systematically reviewed randomized controlled trials (RCTs) in patients with LAPC treated with standard care (radical prostatectomy, radiotherapy, and/or watchful waiting) or standard care plus hormonal treatment. Outcomes assessed were mortality and objective disease progression. The meta-analysis used a fixed-effects model. RESULTS Of the 108 trials identified, seven met the inclusion criteria and were of sufficient quality to be included in the analysis. Early intervention with hormonal treatment significantly reduced all-cause mortality compared with deferred treatment (relative risk, RR, 0.86; 95% confidence interval, CI, 0.82,0.91; P < 0.001). Similarly, early vs deferred use of hormonal treatment significantly reduced: prostate cancer- specific mortality (RR 0.72; 95% CI 0.65,0.79); overall progression (RR 0.74; 0.69,0.78); local progression (RR 0.65; 0.57,0.73); and distant progression (RR 0.67; 0.61,0.74; all P < 0.001). Results were robust to changes in inclusion/exclusion criteria and use of a random-effects model for the meta-analyses. Heterogeneity and publication bias had no significant effect on the analyses. CONCLUSIONS Early intervention with hormonal treatment for patients with LAPC provides significantly lower mortality and objective disease progression than deferring their use until standard care has failed. [source] Comparison of the clinical outcome after hormonal therapy for prostate cancer between Japanese and Caucasian menBJU INTERNATIONAL, Issue 6 2006TAKASHI FUKAGAI OBJECTIVE To investigate the impact of race on the effectiveness of hormonal therapy in patients with prostate cancer, by comparing the outcomes of Caucasian men (CM) and Japanese-American men (JAM) treated with hormonal therapy at one institution. PATIENTS AND METHODS Fifty-nine CM and 105 JAM with prostate cancer were treated with hormonal therapy at The Queen's Medical Center in Honolulu. Age, stage, Gleason score, race, and pretreatment PSA levels were abstracted. The Kaplan,Meier method was used to construct overall and cause-specific survival curves, which were compared using log-rank statistics. These factors were assessed as to their interdependence and correlation with the clinical course using a Cox proportional hazards regression model. RESULTS Although there were no statistical differences in patient background, JAM who had received hormonal treatment had a better outcome than CM for overall and cause-specific survival rate (P = 0.001 and 0.036, respectively). Race was one of the significant prognostic factors in the multivariate analysis (P = 0.03). The findings suggest a difference in the effectiveness of hormonal therapy for prostate cancer in JAM living in Hawaii compared to CM. CONCLUSIONS There were marked racial differences in clinical outcome after hormonal therapy between JAM and CM. A prospective study with more patients might be necessary to elucidate the differential effectiveness of hormonal therapy for prostate cancer in different races, especially between Japanese and Caucasians. [source] Infertility despite surgery for cryptorchidism in childhood can be classified by patients with normal or elevated follicle-stimulating hormone and identified at orchidopexyBJU INTERNATIONAL, Issue 7 2003D. Cortes OBJECTIVE To analyse infertility despite orchidopexy in childhood. PATIENTS AND METHODS The study comprised patients with cryptorchidism (70 bilateral and 65 unilateral) who had a simultaneous biopsy taken at orchidopexy in childhood, and in adulthood had analyses of semen and FSH. In adulthood 42 formerly bilateral cryptorchid boys had repeat testicular biopsies taken. Infertility was suspected in men with < 5 million sperm/mL in the best sample of semen and concomitant poor sperm motility, and who were classified by follicle-stimulating hormone (FSH) values. At orchidopexy the number of spermatogonia/tubule and the germ cell differentiation were measured. In adulthood the percentage of tubules with complete spermatogenesis, spermatogenic arrest and Sertoli-cell only status was assessed. RESULTS Infertility was suspected in 38 of 70 (54%) of formerly bilateral and six of 65 (9%) formerly unilateral cryptorchid patients. High FSH values were expected in these suspected infertile patients, but 15 of 38 (59%) formerly bilateral and five of six formerly unilateral cryptorchid patients had normal FSH values. These patients were identified in childhood at orchidopexy; those with bilateral cryptorchidism generally presented with germ cells, but the mean number of spermatogonia per tubule was < 30% of the lowest normal value, and the germ cells were seldom normally differentiated, whereas those with unilateral cryptorchidism generally lacked germ cells in the biopsies. No patients had a decreased FSH value. CONCLUSION Despite surgery for cryptorchidism, infertility was probable in a third (44 of 135) of the patients. We expected high FSH values in these patients, but in 45% (20/44) the FSH values were normal. These patients may have relative FSH deficiency. At orchidopexy these patients were identified to be bilaterally cryptorchid with few germ cells and those unilaterally cryptorchid had none in the biopsy. After orchidopexy in childhood, additional hormonal treatment, e.g. recombinant FSH or buserelin, may be indicated in these patients. [source] Gender change and its impact on the course of multiple sclerosisACTA NEUROLOGICA SCANDINAVICA, Issue 5 2006D. Reske We report the case of a 22-years old genotypic women suffering from a relapsing-remitting multiple sclerosis (MS) according to the Poser criteria. In this patient, a gender change had been performed by androgen-supplementation and surgical intervention. During gender change, the patient experienced further relapses. Different immunomodulatory and immunosuppressive treatment strategies did not stabilise the course of MS in this patient. Actually, an escalating therapy with mitoxantrone has been initiated. During the observation period the patient received long-term testosterone-supplementation. Testosterone levels were elevated in the serum of this genotypic female MS patient under such a hormonal treatment compared to normal ranges before. The clinical course of the patient is presented in this case. As there are several studies investigating an immunomodulatory impact of hormones on the course of MS or experimental allergic encephalomyelitis, we discuss the presented case and a possible influence of androgens in this patient. [source] Bipolar disorder in women: reproductive events and treatment considerationsACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2005M. P. Freeman Objective:, Bipolar disorders are prevalent in women. Women with bipolar disorder often present with different clinical features than men. Reproductive events and hormonal treatments may impact the course of bipolar disorder. Our main objectives are to i) assess the impact of reproductive events on the course of the disorder, and ii) to discuss the relationships between reproductive events and psychiatric treatments. Method:, A literature search was conducted of MEDLINE journals from 1965 to present. Manual literature searches were also conducted. We review the presentation, clinical course, and treatment considerations of bipolar disorder in women, with emphasis on treatment considerations in the context of reproductive events. Treatment-related issues such as teratogenicity, breastfeeding, polycystic ovarian syndrome, weight gain and obesity, and medication interactions with oral contraceptives are reviewed. Results:, Women with bipolar disorder may be more vulnerable to mood episodes in the context of reproductive events, particularly postpartum. In women of reproductive age, mood stabilizers must be selected with teratogenic risks in mind, with the highest reported risks in pregnancy with valproate, and the greatest concern during breastfeeding with lithium use. In the areas of the perimenopause and polycycstic ovarian syndrome, more data are needed to advise treatment decisions. Conclusion:, We urgently need further study in these areas to deliver care that is appropriate to women with bipolar disorder. [source] Steroid hormone receptors and coregulators in endocrine-resistant and estrogen-independent breast cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 4 2006Nanna Sarvilinna Abstract Resistance to hormonal therapy is often a problem in the treatment of breast cancer patients. It has been suggested that resistance could be explained by altered nuclear hormone receptor or coregulator levels or inappropriately increased agonist activity of selective estrogen receptor modulator (SERM). To test these hypotheses, we have established novel MCF-7 cell line-derived in vitro models of anti-estrogen- and progestin-resistant and estrogen-independent breast cancer by long-term culture in the presence of toremifene and medroxyprogesterone acetate (MPA) and in the absence of estradiol, respectively. Using cell growth and multiprobe ribonuclease protection assays, the expression of 5 nuclear hormone receptors and 9 coregulators as well as the alterations in the cell proliferation and target gene transcription in response to hormonal treatments were studied. Progesterone receptor (PR) expression was decreased and silencing mediator for retinoid acid and thyroid hormone receptors (SMRT) and amplified in breast cancer-1 (AIB1) expression increased in anti-estrogen-resistant cells. Estrogen caused PR and ER, upregulation in all cell lines, but we did not observe increased agonist activity of anti-estrogen measured by regulation of these estrogen target genes. Basal ER, levels and estrogenic growth response were decreased and p300/CBP-associated factor (pCAF) and AIB1 upregulated by estrogen in progestin-resistant cells, but coregulator levels were unchanged. Estrogen-independent cells were still estrogen-responsive and PR, nuclear receptor corepressor (N-CoR) and SMRT expression was increased whereas steroid receptor coactivator-1 (SRC-1a) and CBP-related protein p300 (p300) expression decreased. Their growth was inhibited by toremifene, but estradiol was able to abrogate this effect, which might have interesting clinical implications concerning the use of postmenopausal hormone replacement therapy. © 2005 Wiley-Liss, Inc. [source] Age-related histopathological lesions in the Mongolian gerbil ventral prostate as a good model for studies of spontaneous hormone-related disordersINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2008Silvana Gisele Pegorin Campos Summary The Meriones unguiculatus (Mongolian) gerbil has demonstrated significant prostatic responses to hormonal treatments, and to drugs against human prostatic hyperplasia Spontaneous neoplasia develops in the older animals. Thirty gerbils (age 18 months) were divided into non-affected and prostatic lesion bearers and the prostate lesions were evaluated morphologically, immunohistochemically and quantitatively. The most frequent changes were in epithelial sites and, namely prostatic intraepithelial neoplasias, microinvasive carcinomas and adenocarcinomas. In the stromal compartment, cellular hyperplasia, when verified, was always associated with the sites of anomalous epithelium. Additionally, larger deposition of collagen fibrils, generating stromal fibrosis, was found in all the old gerbils analysed. The quantitative analysis showed that prostatic tissue proportions differed in altered areas, being specific for each lesion type. Isolated nuclear and nucleolar parameters were not effective in diagnosing the malign potential of lesions. However, the cellular proliferation and death indexes indicated larger cellular turnover in invasive lesions such as carcinomas. With these analyses, it could be verified that old gerbils present high propensity to develop spontaneous prostate changes and this may aid in a better understanding of the biological behaviour of human prostate cancer. [source] Effect of Oxygen Saturation in Water on Reproductive Performances of Pacu Piaractus brachypomusJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 4 2003Konrad Dabrowski Broodstock pacu Piaractus brachypomus as well as their eggs during their embryonic development were exposed to either normoxia (5.5,7.5 mg O2/L) or hypoxia (2.0,4.5 mg O2/L) conditions. The plasma concentrations of 11-ketotestosterone in males and estradiol-17, in females, as well as that of their precursor testosterone (T) were significantly (P < 0.01) higher in fish maintained under normoxic conditions than in fish exposed to hypoxia. After ovulation and spermiation induced by hormonal treatments, the plasma concentrations of T and 17,20,-dihydroxy-4-pregnen-3-one (17,20,P) significantly (P 0.05) increased in both sexes under both normoxic and hypoxic conditions. The plasma levels of T and 17,20,P achieved under normoxic conditions were higher than the ones recorded under hypoxia, except for those of 17,20,P in males. Males responded positively to the hormonal treatments, and the concentration of spermatozoa was 10.5 ± 0.8 109/mL under both oxygen conditions. Hypoxia resulted in significantly lower survival of embryos (17.3 ± 28%) in comparison to normoxic conditions (68.5 ± 25%). Moreover, larval deformities were found when exposed to hypoxia (91.6 ± 6%). During embryonic development of this species 4 mg/L of oxygen is tolerated at 26,27 C without negative impact. We conclude that despite the highly adaptable nature of adult pacu to environmental hypoxia, oxygen concentrations below 4 mg/L severely impacted survival of embryos. [source] Differential expression and activation of Stat3 during mouse embryo implantation and decidualizationMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 1 2004Chun-Bo Teng Abstract Signal transducer and activator of transcription (STATs) can be activated by many cytokines and growth factors. Stat3, a member of STAT family, is essential for embryonic development. Stat3 is specifically activated during mouse embryo implantation. This study was to investigate the expression, activation, and regulation of Stat3 in mouse uterus during early pregnancy, pseudopregnancy, delayed implantation, artificial decidualization, and hormonal treatments using in situ hybridization and immunohistochemistry. There was a strong level of Stat3 phosphorylation in the luminal epithelium only at the midnight of day 4 pregnancy, which coincides with attachment reaction between the blastocyst and luminal epithelium. However, there was no detectable Stat3 phosphorylation at the corresponding period during pseudopregnancy. On day 5 of pregnancy, Stat3 phosphorylation was strongly observed in the luminal epithelium and the stroma surrounding the implanting blastocyst at implantation sites, but not at the inter-implantation sites. Stat3 phosphorylation was also not detected on day 5 of pseudopregnancy. Stat3 phosphorylation was at a high level in the decidual cells on days 6,8 of pregnancy. Under artificial decidualization, Stat3 was also phosphorylated in the decidual cells. In the ovariectomized mice, there was no Stat3 expression and activation in the uterus. Progesterone had no obvious effects. However, Stat3 mRNA expression and phosphorylation were significantly stimulated by estrogen treatment. Our data suggest that Stat3 phosphorylation may be important for mouse embryo implantation and decidualization, and may also be regulated by maternal estrogen. Mol. Reprod. Dev. 69: 1,10, 2004. © Wiley-Liss, Inc. [source] Developmental Changes in Effect of Cytokinin and Gibberellin on Shoot K+ and Na+ Accumulation in Salt-Treated Sorghum PlantsPLANT BIOLOGY, Issue 4 2001G. N. Amzallag Abstract: The effect of cytokinin (CK) and/or gibberellin (GA) treatments on shoot accumulation of Na+ and K+ was investigated in Sorghum bicolor exposed to 150 mM NaCl. These hormonal treatments modified the shoot content of Na+ and K+, but the effect varied throughout development. Comparison of ion concentration versus ion content in shoots indicates that regulation of shoot concentration of K+ is modified during a transition period of development. This change is concomitant with reorganization of the regulation network for meristem activity, an event also involving changes in sensitivity to CK and GA. This evidence suggests a strong interdependency between dynamic changes in a between-organ network of relations and control of accumulation of monovalent ions in the shoot. Moreover, a new pattern of regulation of shoot Na+ concentration emerges during the transition period. During this process GA appears progressively involved in regulation of Na retranslocation, while CK is rather controlling the root uptake of Na+. Accordingly, the spontaneous emergence of Na-includer and Na-excluder individuals observed from an initially homogeneous population is interpreted as related to variations in sensitivity to GA and CK during differentiation of this newly emerging pathway of regulation. [source] Procedure for Maximizing Oocyte Harvest for In Vitro Embryo Production in Small RuminantsREPRODUCTION IN DOMESTIC ANIMALS, Issue 4 2007A Gibbons Contents Possible effects of repeated hormonal treatments and laparoscopic ovum pick-up (LOPU) on the efficiency of oocyte recovery rate and quality were determined in sheep and goats. In six adult Merino sheep and five Criolla goats, ovarian status was synchronized by a prostaglandin F2, analogue and the insertion of an intravaginal sponge 48 h later. Follicle development was stimulated by a single dose of FSH (60 mg NIH-FSH-P1) plus a single dose of equine chorionic gonadotrophin (eCG; 300 UI). The first FSH/eCG doses were administered 48 h after the sponge insertion, being repeated every 4 days to complete a total of four treatments in sheep and three in goats. Follicles in both ovaries were categorized according to their diameter and follicular fluid was aspirated under laparoscopic observation without a vacuum pump. In sheep, during a 12-day-period, a total of 347 follicles were aspirated with a recovery rate of 46.9%. In goats, during an 8-day-period, 219 follicles were aspirated with a recovery rate of 45.6%. In both species, there were no significant differences in the number of aspirated follicles, oocyte recovery rate and good quality oocyte recovery rate. However, in sheep the oocyte recovery rate was higher for large follicles, whereas in goats no such effect was detected. In summary, current results indicate that retrieval of oocytes can be maximized, without affecting oocyte quality, by repeating ,oneshot' FSH/eCG regimes and LOPUs at intervals as short as 4 days. [source] Oestradiol Induced Inhibition of Neuroendocrine Marker Expression in Leydig Cells of Adult RatsREPRODUCTION IN DOMESTIC ANIMALS, Issue 3 2006HH Ortega Contents The objectives of this work were to determine the changes in the expression of neuroendocrine markers in Leydig cell by oestradiol treatment, and to determine whether testosterone is able to recover partially the effects of hormonal suppression induced by oestradiol. Adult male rats were injected daily with either 50 ,g of oestradiol or oestradiol plus testosterone propionate (25 mg every 3 days) for 15 days. The animals were sacrificed and testicles were dissected and processed by routine histological protocols. FSH and LH serum levels were determined by radioimmunoassay. The visualization of antigens was achieved by the streptavidin-peroxidase immunohistochemical method. Antibodies against chromogranin A (CrA), S-100 protein (S-100), P substance (PS), synaptofisin (SYN), neurofilament protein (NF), gliofibrillary acidic protein (GFAP) and neuron specific enolase (NSE) were used. The mean LH and FSH serum concentrations were consistently suppressed with hormonal treatments. Intermediate filaments (NF and GFAP) showed no difference in their expression. The expression of S-100, NSE and SYN was significantly lower in both hormone-treated groups. In oestradiol-treated rats, the immunoreactivity of CrA and SP decreased significantly but was restored after testosterone supplementation. Although the nature and functions of many of these substances in Leydig cells remain unknown, these results are consistent with the hypothesis that the expression of some neuroendocrine markers is hormonally controlled. [source] | ||||||||||||||||||||||||||||||||||