PURPOSE: Docetaxel-based chemotherapy (DTX) improves overall survival (OS) of men with metastatic castration-resistant prostate cancer (mCRPC). Considering the potential existence of androgen receptors that remain active at this stage, we aimed to assess the impact of the combined use of androgen deprivation therapy (ADT) with DTX for mCRPC. MATERIALS AND METHODS: We performed a single-institutional retrospective analysis of patients with mCRPC who received either DTX alone (DTX group, n=21) or concurrent DTX and ADT (DTX+ADT group, n=26) between August 2006 and February 2014. All patients received DTX doses of 75 mg/m2 every three weeks for at least three cycles. In the DTX+ADT group, all patients used luteinizing hormone releasing hormone agonist continuously as a concurrent ADT. RESULTS: The median follow-up period was 24.0 months (interquartile range 12.0-37.0) for the entire cohort. The median radiographic progression-free survival (rPFS) was 9.0 months and 6.0 months in the DTX+ADT and DTX groups, respectively (log-rank p=0.036). On multivariable Cox regression analysis, concurrent administration of ADT was the only significant predictor of rPFS [hazard ratio (HR)=0.525, 95% confidence intervals (CI) 0.284-0.970, p=0.040]. The median OS was 42.0 and 38.0 months in the DTX+ADT and DTX groups, respectively (log-rank p=0.796). On multivariable analysis, hemoglobin level at the time of DTX initiation was associated with OS (HR=0.532, 95% CI 0.381-0.744, p<0.001). CONCLUSION: In chemotherapy-naive patients with mCRPC, the combined use of ADT with DTX improved rPFS. Our result suggests that the concurrent administration of ADT and DTX is superior to DTX alone.
Adenocarcinoma/blood/*drug therapy/secondary ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Disease-Free Survival ; Gonadotropin-Releasing Hormone/administration & dosage/agonists ; Hemoglobins/metabolism ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms, Castration-Resistant/blood/*drug therapy/pathology ; Retrospective Studies ; Survival Rate ; Taxoids/administration & dosage

Long-term gonadotropin-releasing hormone agonist (GnRHa) administration before in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in infertile women with endometriosis or adenomyosis significantly enhanced the chances of pregnancy in both fresh and frozen embryo transfer cycles. We hypothesized that long-term GnRHa treatment might also be beneficial for the idiopathic repeated implantation failure (RIF) patients. In the 21 patients receiving GnRHa and hormone replacement therapy (G-HRT) protocols for frozen embryo transfer, their data were compared with those of the 56 of frozen/fresh cycles they had previously undergone (previous protocols). Comparison showed that the finial results were significantly better with G-HRT protocols than with their previous protocols, with pregnancy rate, clinical pregnancy rate, implantation rate and on-going pregnancy rate being 70%, 60%, 40% and 38% respectively with G-HRT protocols, against 17%, 11%, 6.3% and 5% with previous protocols. The results showed that hormonally controlled endometrial preparation with prior GnRHa suppression could be used for patients who had experienced repeated failures of IVF treatment despite having morphologically optimal embryos, and the treatment may help increase the receptivity of the endometrium in these patients.
Adult ; Embryo Implantation ; drug effects ; Embryo Transfer ; methods ; Female ; Gonadotropin-Releasing Hormone ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Hormone Replacement Therapy ; methods ; Humans ; Pituitary Gland ; drug effects ; Pregnancy ; Sperm Injections, Intracytoplasmic ; methods

The effects of fluoride exposure on the functions of reproductive and endocrine systems have attracted widespread attention in academic circle nowadays. However, it is unclear whether the gene-environment interaction may modify the secretion and activity of hypothalamus-pituitary- ovarian (HPO) axis hormones. Thus, the aim of this study was to explore the influence of fluoride exposure and follicle stimulating hormone receptor (FSHR) gene polymorphism on reproductive hormones in Chinese women. A cross sectional study was conducted in seven villages of Henan Province, China during 2010-2011. A total of 679 women aged 18-48 years were recruited through cluster sampling and divided into three groups, i.e. endemic fluorosis group (EFG), defluoridation project group (DFPG), and control group (CG) based on the local fluoride concentration in drinking water. The serum levels of gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were determined respectively and the FSHR polymorphism was detected by real time PCR assay. The results provided the preliminary evidence indicating the gene-environment interaction on HPO axis hormones in women.
Adolescent ; Adult ; Age Factors ; Asian Continental Ancestry Group ; China ; Cross-Sectional Studies ; Estradiol ; blood ; Female ; Fluoridation ; adverse effects ; Fluorides ; administration & dosage ; adverse effects ; urine ; Follicle Stimulating Hormone ; blood ; Gene-Environment Interaction ; Gonadotropin-Releasing Hormone ; blood ; Humans ; Hypothalamus ; physiology ; Luteinizing Hormone ; blood ; Middle Aged ; Ovary ; physiology ; Pituitary Gland ; physiology ; Polymorphism, Single Nucleotide ; Receptors, FSH ; genetics ; Tobacco Smoke Pollution ; Young Adult

The objective of this study was to investigate factors that influence the success of resynchronization protocols for bovines with and without progesterone supplementation. Cow synchronized and not found pregnant were randomly assigned to two resynchronization protocols: ovsynch without progesterone (P4) supplementation (n = 66) or with exogenous P4 administered from Days 0 to 7 (n = 67). Progesterone levels were measured on Days 0 and 7 of these protocols as well as 4 and 5 days post-insemination. Progesterone supplementation raised the P4 levels on Day 7 (p < 0.05), but had no overall effect on resynchronization rates (RRs) or pregnancy per artificial insemination (P/AI). However, cows with Body Condition Score (BCS) > 3.5 had increased P/AI values while cows with BCS < 2.75 had decreased P/AI rates after P4 supplementation. Primiparous cows had higher P4 values on Day 7 than pluriparous animals (p = 0.04) and tended to have higher RRs (p = 0.06). Results of this study indicate that progesterone supplementation in resynchronization protocols has minimal effects on outcomes. Parity had an effect on the levels of circulating progesterone at initiation of the protocol, which in turn influenced the RR.
Animals ; Cattle/*physiology ; Dinoprost/administration & dosage/*pharmacology ; Estrus Synchronization/*drug effects/methods ; Female ; Fertility Agents/administration & dosage/pharmacology ; Gonadotropin-Releasing Hormone/administration & dosage/*pharmacology ; Insemination, Artificial/veterinary ; Ovulation/drug effects ; Pregnancy ; Progesterone/administration & dosage/*pharmacology ; Tromethamine/administration & dosage/*pharmacology

BACKGROUNDAs a Chinese Traditional Medicine product, Kuntai capsule could improve the peri-menopausal symptoms in postmenopausal women. But it is still not clear whether Kuntai capsule has a good effect on alleviating peri-menopausal symptoms induced by gonadotropin releasing hormone agonist (GnRH-a) treatment. The purpose of this study was to investigate the clinical effectiveness and safety of Kuntai capsule, on peri-menopausal symptoms in endometriosis (EMS) patients, with postoperative GnRH-a treatment.

METHODSNinety EMS ovarian cyst women with postoperative GnRH-a administration were enrolled in the study, and were randomly divided into Kuntai group, Tibolone group, or blank Control group. The therapeutic strategy in Kuntai group was 4 Kuntai capsules tid,po for 12 weeks after the first GnRH-a injection, while Tibolone 2.5 mg qd, po for 12 weeks in Tibolone group. There was no drug addition in Control group. Climacteric complaints were evaluated by Kupperman menopausal index (KMI) and hot flash/sweating score. Liver and renal functions, lipid profile, serum sex hormone levels and endometrial thickness were measured, and the frequency of adverse events in Kuntai and Tibolone groups was recorded.

RESULTS(1) Before GnRH-a therapy, the baseline parameter results were comparable in the three groups (P > 0.05). (2) After GnRH-a therapy, KMI and hot flash/sweating scores in all the three groups increased significantly (P < 0.05). At the 4 th week after GnRH-a therapy, KMI and hot flash/sweating score results were as follows: Control group > Kuntai group > Tibolone group (P < 0.05); at the 8 th and 12 th week after GnRH-a therapy, KMI and hot flash/sweating score in Control group were significantly higher than the other two groups (P < 0.05), and no significant difference was identified between Kuntai and Tibolone group (P > 0.05). (3) No statistical change took place in the liver and renal functions and lipid profile in all the three groups after the treatment (P > 0.05). (4) The posttherapeutic serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) level and endometrial thickness decreased significantly in all the three groups (P < 0.05). After therapy, serum E2 level in Tibolone group was obviously higher than the other two groups (P < 0.05), while FSH and LH levels were obviously lower (P < 0.05). (5) The incidence of vaginal bleeding, breast distending pain in Tibolne group was obviously higher than Kuntai group (P < 0. 05).

CONCLUSIONSKuntai capsule is effective on the peri-menopausal symptoms induced by postoperative GnRH-a administration to EMS patients, although its clinical effect might be a few weeks later than Tibolone. Kuntai capsule might be a little safer than Tibolone tablet.

Adult ; Double-Blind Method ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; therapeutic use ; Endometriosis ; drug therapy ; Endometrium ; drug effects ; pathology ; Female ; Gonadotropin-Releasing Hormone ; agonists ; Goserelin ; therapeutic use ; Humans ; Norpregnenes ; therapeutic use ; Young Adult

OBJECTIVETo evaluate the effect of combined use of stanazolol (ST) on the final adult height (FAH) in girls with idiopathic central precocious puberty (ICPP) and apparently decreased linear growth during gonadotropin-releasing hormone analog (GnRHa) therapy.

METHODSixty-three girls with ICPP and decreased velocity of growth of height (HV<4 cm/yr) during GnRHa therapy were divided into 3 groups based on the following types of interventions:group 1 (n = 20), GnRHa+ST [25-30 µg/(kg·d) every 3-month followed by 3-month discontinuation], group 2 (n = 21), GnRHa+recombinant human growth hormone [rhGH, 1-1.1 U/(kg·w)], group 3 (n = 22), GnRHa alone.HV, the advancement of bone age (BA) for chronological age (CA) (ΔBA/ΔCA) and FAH were compared among groups.

RESULT(1)Total duration of ST combination therapy was (12.22 ± 3.62) months, while total duration of combination of rhGH was (13.22 ± 6.80) months. (2)HV increased significantly in both group 1 [ (2.79 ± 0.60) cm/yr vs. (6.27 ± 1.98) cm/yr, P < 0.01] and in group 2 [(2.80 ± 0.50) cm/yr vs. (6.25 ± 1.98) cm/yr, P < 0.01] during combined therapy, but maintained at low levels in group 3 [(3.95 ± 1.10) cm/yr vs. (3.34 ± 0.95) cm/yr, P > 0.05].No significant differences of ΔBA/ΔCA were found among the three groups [0.25(0.11∼0.28), 0.22(0.15∼0.31),0.19(0.10∼0.32), P > 0.05]. (3)FAH was significantly higher than predicted adult height (PAH) before combined therapy, as well as higher than target height (THt) in both group 1 [(156.25 ± 2.90) cm vs. (150.78 ± 3.70) cm, P < 0.01, (156.25 ± 2.90) cm vs. (153.94 ± 2.62) cm, P < 0.01], and in group2 [ (157.33 ± 4.69) cm vs. (152.61 ± 3.92) cm, P < 0.01, (157.33 ± 4.69) cm vs. (154.39 ± 4.72) cm, P = 0.01].In group 3, FAH was similar to PAH [(153.88 ± 2.6) cm vs. (152.54 ± 5.86) cm, P > 0.05], and was less than THt [(153.88 ± 2.6) cm vs. (155.60 ± 4.52) cm, P = 0.02]. (4)In girls treated with ST, no hirsutism, clitorism or hoarse voice was recorded.No polycystic ovary syndrome was found by B-mode ultrasound.

CONCLUSIONIntermittent combined use of low dose ST therapy can increase HV and thus improve FAH in girls with ICPP and apparently decreased linear growth during GnRHa therapy.

Body Height ; drug effects ; Bone Development ; Child ; Child Development ; drug effects ; Drug Therapy, Combination ; Female ; Gonadotropin-Releasing Hormone ; administration & dosage ; analogs & derivatives ; therapeutic use ; Growth Disorders ; drug therapy ; Human Growth Hormone ; administration & dosage ; therapeutic use ; Humans ; Puberty, Precocious ; drug therapy ; physiopathology ; Stanozolol ; administration & dosage ; therapeutic use ; Treatment Outcome

This paper was aimed to study the minimum dose of human chorionic gonadotropin (hCG) to effectively trigger maturation of oocytes and prevent ovarian hyperstimulation syndrome (OHSS) in a series of hyper-responders treated with a long gonadotropin releasing hormone agonist (GnRHa) protocol. Six women at high risk of developing severe OHSS in a long GnRHa protocol were enrolled into this study. Serum hormone levels on the day of and after hCG administration, antral follicle count, oocyte retrieval number and quality were determined. In total, 6 women aged between 29 and 36 years and at risk of developing severe OHSS, received 2000 U hCG. Five of them were treated with coasting for 1 day and the rest one for 4 days. The mean number of oocytes collected was 19 (range 14-27) and the fertilization rate per collected oocyte was 72.81%. Of the 6 women in the study, only one cancelled embryos transfer and all embryos were frozen, and then she delivered two health boys on term in the subsequent frozen-thawed embryo transfer (FET) cycle. Pregnancies and births were achieved in 3 patients out of 5 in vitro fertilization-embryo transfer (IVF-ET) cycles. No woman developed moderate or severe OHSS. Triggering with 2000 U hCG is feasible to prevent OHSS in unpredicted hyper-responders undergoing IVF in a long GnRHa protocol.
Adult ; Chorionic Gonadotropin ; administration & dosage ; adverse effects ; Dose-Response Relationship, Drug ; Female ; Fertility Agents, Female ; administration & dosage ; Gonadotropin-Releasing Hormone ; antagonists & inhibitors ; Humans ; Infertility, Female ; therapy ; Oocytes ; drug effects ; pathology ; Ovarian Hyperstimulation Syndrome ; etiology ; prevention & control ; Ovulation Induction ; adverse effects ; methods ; Treatment Outcome

OBJECTIVETo investigate the value of serum estradiol increment and serum estradiol/follicles on the day of hCG administration in predicting the clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET).

METHODSA retrospective analysis of the IVF-ET data was conducted involving 121 patients who received a long gonadotrophin-releasing hormone agonist (GnRHa) protocol. According to the increment of serum estradiol on the day of hCG administration (relative to the level on the day before hCG administration), the patients were divided into 3 groups (A1, A2 and A3) with a increment ratio below 30%, between 30% and 50%, and over 50%, respectively. In addition, according to the ratio of serum estradiol level on hCG day to mature follicle (diameter ≥ 14 mm) number, these patients were divided into three groups (B1, B2 and B3) with the ratio below 250 pg/ml, between 250 and 350 gp/ml, and over 350 pg/ml, respectively. The hormonal characteristics and clinical outcomes of the IVF-ET cycles were analyzed comparatively.

RESULTSBoth the clinical pregnancy rate (71.05%) and embryo implantation rate (52.63%) were significantly higher in group A3 than in groups A1 and A2 (P<0.05). The best clinical pregnancy rate (67.86%) and embryo implantation rate (49.14%) were significantly higher in group B2 than in groups B1 and B3 (P<0.05).

CONCLUSIONThe variation of serum estradiol shows an important impact on the clinical outcomes of IVF-ET in patients receiving long GnRH-a protocol. Favorable outcomes can be expected with a hCG day serum estradiol increment ratio above 50% and E(2)/follicle ratio between 250 and 350 pg/ml.

Embryo Transfer ; Estradiol ; blood ; Female ; Fertility Agents, Female ; administration & dosage ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone ; administration & dosage ; agonists ; Humans ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Treatment Outcome

Several case reports have indicated that a small subgroup of patients may develop ovarian hyperstimulation following the administration of gonadotropin-releasing hormone agonists (GnRHa) without gonadotropins. However, since only few such cases have been published, it is unclear what course to follow in subsequent cycles after ovarian hyperstimulation in the first cycle using only GnRHa. A 33-yr-old woman was referred to in vitro fertilization for oocyte donation. A depot preparation (3.75 mg) of tryptorelin without gonadotropins induced ovarian multifollicular enlargement with high estradiol level, and was followed by human chorionic gonadotropin administration and oocyte retrieval. In a subsequent cycle of the same patient, a low dose of tryptorelin (0.05 mg) did not induce ovarian hyperstimulation, and resulted in clinical pregnancy. This report shows potential management of ovarian hyperstimulation following the administration of GnRHa without gonadotropins.
Adult ; Chorionic Gonadotropin/administration & dosage ; Female ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone/*agonists ; Humans ; *Oocyte Donation ; Oocyte Retrieval ; Ovarian Hyperstimulation Syndrome/*chemically induced ; Ovary/*drug effects ; Ovulation Induction/methods ; Pregnancy ; Triptorelin Pamoate/*administration & dosage/adverse effects

OBJECTIVETo evaluate the effects of levonorgestrel-releasing intrauterine system (LNG-IUS) combined with GnRH analogue (GnRH-a) in the treatment of adenomyosis with uterine body enlargement.

METHODSTwelve women (mane age 40.3 years) with adenomyosis and uterine cavity depth over 11 cm received injections of GnRH-a every 4 weeks, and after the uterine cavity depth was reduced to below 10 cm, LNG-IUS was deployed. VAS pain score, PBAC bleeding score, uterine volume, and hemoglobin levels of the women were measured before the treatment and at 6 and 12 months after LNG-IUS placement.

RESULTSThe VAS pain score was significantly lowered at 6 and 12 month after LNG-IUS placement (P<0.05), and the PBAC bleeding score also showed significant reductions (P<0.05). The uterine volume decreased significantly at 6 and 12 months after LNG-IUS placement as compared with that before the treatment, but was significantly greater at 6 month in comparison with that at the time of LNG-IUS placement (P<0.05). Serum hemoglobin levels underwent significant increments after LNG-IUS placement (P<0.05).

CONCLUSIONLNG-IUS combined with GnRH analogue injection can be effective in the treatment of adenomyosis with dysmenorrhea and hypermenorrhea.

Adult ; Delayed-Action Preparations ; administration & dosage ; Drug Therapy, Combination ; Endometriosis ; drug therapy ; Female ; Gonadotropin-Releasing Hormone ; analogs & derivatives ; therapeutic use ; Humans ; Levonorgestrel ; administration & dosage ; Uterine Diseases ; drug therapy