Luteinizing Hormone-releasing Hormone Analogue Treatment Research Articles

Subcapsular orchiectomy versus total orchiectomy and LHRH analogue in the treatment of hormone-sensitive metastatic prostate cancer: a different perspective in evaluation of the psychosocial effects.

We aimed to compare total orchiectomy, subcapsular orchiectomy, and luteinizing hormone-releasing hormone (LHRH) analogue treatment in patients with hormone-sensitive metastatic prostate cancer in terms of efficacy of androgen deprivation treatment (ADT), patient satisfaction, health-related quality of life (HRQoL), development of phantom testis syndrome (PTS), and post-traumatic stress disorder (PTSD). Among 272 patients treated between July 2015 and January 2019, 189 patients were enrolled in this prospective, cohort study and the patients were divided into three groups: group I, bilateral total orchiectomy (n 66); group II, bilateral subcapsular orchiectomy (n 63); and group III, LHRH analogue treatment (n 60). The adequacy of ADT was routinely monitored every 3months and clinical parameters were evaluated. After 6 to 36months following ADT, questionnaires were used to evaluate PTS, PTSD, and HRQoL during outpatient visits. The patient satisfaction was questioned as yes/no. Adequate castration was provided with all three treatments, while the presence and frequency of PTS and severity of PTSD were lower, and patient satisfaction related to ADT and all components of HRQoL were better in patients undergoing subcapsular orchiectomy than those undergoing total orchiectomy. All findings except for PTS were similar in patients undergoing subcapsular orchiectomy and LHRH analogue treatment. In analysis of all patients, total incidence of PTS was 43.4% and PTSD was reported to be 48.7%. A strong relationship was found between PTSD and phantom testis pain (r 0.621, p < 0.001). Subcapsular orchiectomy has less psychosocial side effects than total orchiectomy and is similar to LHRH analogue treatment. It can be a reliable, cheaper, and fast-acting alternative to LHRH analogue treatment.

Effect of cimicifuga racemosa on menopausal syndrome caused by LHRH-a in breast cancer

Ethnopharmacological relevanceCimicifuga racemose is previously proved effective on nature menopausal syndrome (MPS). However, its clinical value in treating with MPS induced by luteinizing-hormone releasing hormone analogue (LHRH-a) therapy of pre-/peri-menopausal breast cancer patients is still unknown. Aim of studyThis perspective randomised-design study is to investigate the effect and safety of cimicifuga racemosa on MPS induced by LHRH-a in breast cancer (clinical trial registered: NCT03339882). Materials and methodsBreast cancer patients planning for LHRH-a treatment were randomly divided into 2 groups. The control group which was being treated with the standard treatment of LHRH-a. The other group was being treated with Remifemin, the commercialized product of cimicifuga racemose extract, combined with LHRH-a, called Remifemin group. Our main endpoint was Kupperman menopause index (KMI). Hormone levels in peripheral blood and gynecological complications were also evaluated. ResultsTotally, 85 patients (42 in Remifemin group and 43 in control group) were enrolled in Zhejiang Cancer Hospital. At the 4th, 8th and 12th week after using LHRH-a, the KMI were all significantly lower in Remifemin group than in control group (P < 0.01), while the hormone levels, including estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were similar in the two groups. In addition, the incidence of cervical cyst in Remifemin group was higher than that in control group (P = 0.02), and there was no significant difference in the other gynecological complications, including endometrial thickening, ovarian cyst or uterine fibroid (P > 0.05). ConclusionsCimicifuga racemose is effective, oncological safe and reliable for treatment of MPS caused by LHRH-a in breast cancer.

Abstract P1-11-11: Cimicifuga racemosa extract prevents menopausal syndrome in LHRHa treatment of breast cancer: A prospective randomized research

Abstract BACKGROUND Menopausal syndrome (MPS) is common in pre/peri-menopausal breast cancer patient receiving luteinizing-hormone releasing hormone analogue (LHRHa). According to the results of TEXT &amp; SOFT study, it could affect patients' life quality seriously and even caused 8%˜23% treatment break. Cimicifuga racemosa (Remifemin) is previously proved effective for MPS in nature menopause patients. We aim to design a prospective randomized research for investigating the effect of Remifemin on MPS which caused by LHRHa in breast cancer (NCT03339882). METHODS The pre/peri-menopausal patients diagnosed as early breast cancer planning for LHRHa were identified and randomly divided into two groups after surgery and chemotherapy if necessary: the Remifemin group (Remifemin 20mg twice a day for 12 weeks) and the control group. The primary endpoint is Kupperman menopause index (KMI). The estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH) levels in blood were also evaluated. RESULTS From January 2017 to December 2017, totally 85 patients (42 in Remifemin group and 43 in control group) were enrolled in Zhejiang Cancer Hospital and there were no significant differences in baseline characteristics including age, BMI, tumor stage, ER, PR, HER2, KMI and hormone levels between two groups (Table 1). At the time of 4, 8, 12 weeks after treatment, the KMI of Remifenmin group were all significantly lower than control group (Table 2, P&amp;lt;0.01) while no significant difference in E2, FSH and LH levels between the two groups (Table 2, P&amp;gt;0.05).There was no significant difference in endometrial thickness, ovarian cyst and Uterine fibroids except cervical cyst (P=0.02). CONCLUSION The use of Remifemin is oncological safe and reliable in preventing MPS which caused by LHRHa in breast cancer. The clinical characteristics of two groups Remifemin groupControl groupP n=42n=43 N(%)N(%) Age(years) 37.74±6.6037.16±6.280.68BMI (body mass index) 21.90±2.8321.65±3.010.69T stage02(4.76)2 (4.65)0.16 113 (30.95)22 (51.16) 227 (64.29)19 (44.19) N stage021 (50.00)24 (55.82)0.63 110 (23.81)12 (27.91) 26 (14.29)5 (11.63) 35 (11.90)2 (4.65) ERPositive30 (71.43)35 (81.40)0.28 Negative12 (28.57)8 (18.60) PRPositive30 (71.43)32 (74.42)0.76 Negative12 (28.57)11 (25.58) HER2Positive8 (19.05)10 (23.26)0.64 Negative34 (80.95)33 (76.74) Category of LHRHaGoserelin32 (76.19)28 (65.12)0.26 Leuprorelin10 (23.81)15 (34.88) Category of endocrine drugNone10 (23.81)6 (13.95)0.20 SERM5 (11.90)11 (25.58) AI27 (64.29)26 (60.47) The endpoints of two groups Remifemin groupControl groupP n=42n=43 KMI*Base line2.45±1.452.30±1.360.62 4th week3.83±1.868.37±4.19&amp;lt;0.01 8th week4.21±1.8011.00±4.48&amp;lt;0.01 12th week4.67±2.1611.98±4.93&amp;lt;0.01E2Base line134.24±64.14143.49±84.190.57 4th week20.26±14.8125.24±13.310.11 8th week13.55±8.1415.65±8.020.23 12th week10.83±7.3512.53±6.350.26FSHBase line8.88±11.4010.17±9.910.58 4th week8.23±9.935.40±6.450.12 8th week4.83±8.496.53±11.500.44 12th week3.65±7.557.28±16.010.19LHBase line6.77±6.319.62±10.590.14 4th week9.08±4.877.93±4.830.28 8th week11.76±11.8210.18±12.210.55 12th week7.27±4.956.90±4.380.72*Wilcoxon test Citation Format: Yu X, Wang C, Liang C, Xuan H, Yang H. Cimicifuga racemosa extract prevents menopausal syndrome in LHRHa treatment of breast cancer: A prospective randomized research [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-11.

566 ANAMEM: Prospective and observational study to evaluate cognitive changes in prostate cancer patients undergoing luteinizing hormone-releasing hormone analogue treatment

INTRODUCTION AND OBJECTIVES: The effect of androgen suppression on cognitive performance (CP) in prostate cancer (PCa) patients is unclear. To date, only 6 small case reports and controlled studies plus 5 cohort studies have been conducted, with inconclusive results. Patient numbers for these studies ranged from 18 to 57 with follow up between 1 and 12 months. This study evaluates changes in cognitive function in a large cohort of PCa patients during their first 6 months of treatmentwith luteinizinghormone-releasinghormone (LHRH)analogues. METHODS: An observational, prospective, multicentre, openlabel study was designed, evaluating CP at baseline and after 6 months of treatment with LHRH analogues. All patients received bicalutamide 50 mg/d 2 weeks before and after the first LHRH analogue administration. CP was evaluated using 5 tests: Digit Subtest of the Wechsler Adult Intelligence Scale (WAIS III-1); Matrices (WAIS III-2); Visual memory test; Line orientation test (Woodward et al.; abridged version); Mental Rotation of tridimensional objects. Improvement (or worsening) of CP tests was statistically significant when corresponding change score was above (or below) the study population upper (or lower) 95% CI bounds. Number and percentage of patients with 1 CP test showing improvement were calculated (overall and subgroups). RESULTS: A cohort of 404 patients was initially screened, 384 received LHRH analogues and 308 completed the study. Median age of patients was 71 years. Overall, in the completer population, 245 patients (79.5%) were unchanged. Of the patients who had changes in CP, the majority were in one test only, for which 59 patients (19.2%) showed improvements and 57 patients (18.5%) showed worsening. Results for individual tests are summarised in the table. Correlations between baseline and 6 months measurements for each test were found to be moderate to strong and statistically significant. No differences in CP in the subgroups studied were observed. CONCLUSIONS: In the ANAMEM study, CP status of patients with PCa is not adversely affected by androgen suppression with LHRH analogues over a period of 6 months.

Use of Channel Catfish, Ictalurus punctatus, Pituitary as a Spawning Aid: Influence of Seasons and Preparations on Efficacy

Channel catfish, Ictalurus punctatus, pituitary powder (CP) was prepared and administered to determine the effect of pituitary preparation, head selection criteria, and season of collection on the biological potency of this gonadotropic preparation. Pituitaries were harvested from three catfish processing plants throughout the months of December, February, March, and April to investigate the effect of season on CP potency. Gravid female channel catfish were injected intraperitoneally (IP) with priming (2 mg/kg) and resolving doses (8 mg/kg) of CP treatments, luteinizing hormone-releasing hormone analog (LHRHa), or saline. Pharmaceutical grade Carbopol 971P resin (CAR) was tested as a 1% aqueous dispersion in physiological saline and administered with CP (10 mg/kg) as a IP single injection at a final volume of 2 mL per kg as a slow-release vehicle. Individual females were hand-stripped, and eggs were fertilized with freshly harvested blue catfish, Ictalurus furcatus, spermatozoa. Pituitaries processed with either acetone or ethanol/acetone resulted in significantly different ovulation rates of 35 and 73%, respectively (P≤ 0.01). Ovulation success was not significantly different among CP and LHRHa treatment groups. Ovulation rates were not significantly different among treatment groups of CP collected in April (74%) or December (67%), or collected from male (69%), or small individuals (55%). The shortest latency period among CP treatment was from CP collected in December and from males at 39.1 ± 0.7 and 38.5 ± 0.4 h, respectively. The CAR vehicle treatment performed poorly resulting in an average ovulation rate of 19.0%, with 3.3% viable embryos at 36 h post-fertilization. Pituitaries collected from channel catfish potentially represent a viable spawning aid for the production of hybrid channel × blue catfish.

Effects of age, weight, hormones, and hibernation on breeding success in boreal toads ( Bufo boreas boreas)

The goals of this study were to test the effects of exogenous hormones and hibernation on breeding behavior and gamete release by boreal toads ( Bufo boreas boreas). Each year, a subset of 77 toads was hibernated and then paired with hibernated or nonhibernated mates and treated with luteinizing hormone releasing hormone analogue (LHRHa), human chorionic gonadotropin (hCG), or left untreated. Amplexus and egg and sperm production were recorded. At 1 yr of age, only 19% of pairs exhibited amplexus, and no sperm or eggs were produced. At 2 and 3 yr of age, most male toads treated with LHRHa exhibited amplexus (56.9% and 100%, respectively). Among 2-yr-old males, amplexus was more prevalent (P < 0.05) in those that were hibernated than in those that were nonhibernated (54.0% and 33.3%, respectively), but most males in each group (93.3% and 75%, respectively) produced sperm in response to LHRHa treatment. Only one 2-yr-old and two 3-yr-old females produced eggs. At 4 yr of age, eight females produced eggs, but two died from egg retention. More nonhibernated than hibernated females developed eggs (7 of 10 vs. 1 of 10, P < 0.05). Mean (±SD) weight of female toads producing eggs (58.9 ± 11.9 g) was greater (P < 0.05) than that of nonproducing females (43.6 ± 7.0 g). Similarly, four of seven nonhibernated females (58.8 ± 8.3 g) produced eggs at 5 yr of age. All eggs were produced by females treated once with LHRHa. Number of eggs per female varied (141 to 3307), and development to tadpoles was low (0 to 36.5%), although tadpoles did become toadlets. In conclusion, male and female boreal toads matured at 2 and 4 yr of age, respectively, and heavier females were more likely to produce eggs. To enhance breeding success, males should be hibernated and treated with LHRHa. In contrast, female productivity was enhanced by improving their body condition instead of subjecting them to hibernation prior to LHRHa treatment.

Long‐term follow‐up of a neoadjuvant chemohormonal taxane‐based phase II trial before radical prostatectomy in patients with non‐metastatic high‐risk prostate cancer

To assess the feasibility and activity of a neoadjuvant treatment combining a luteinizing hormone-releasing hormone (LHRH)-analogue, estramustine and docetaxel before radical retropubic prostatectomy (RRP) in patients with high-risk prostate cancer. High-risk patients were defined as clinical stage > or =T3 and/or a prostate-specific antigen (PSA) level of > or =15 ng/mL, and/or biopsy a Gleason sum of > or =8. Patients received LHRH analogue treatment until the PSA nadir (a stable PSA level for two consecutive determinations) and then, continuing hormone therapy, a combined regimen of estramustine and docetaxel. Patients had RRP within a month of completing the neoadjuvant regimen. All patients were assessed for toxicity and surgical complications. A clinical response was defined as complete (CR, the disappearance of all palpable and radiological abnormalities and a decline in PSA level of > or =90%) or partial (PR, a decline in PSA level of half or more with stable or improved palpable and/or radiological abnormalities). A pathological response was defined as 'complete' (undetectable cancer), 'substantial' (residual cancer in < or =10% of the surgical specimen) or 'minimal' (residual cancer in >10% of the surgical specimen). The biomarkers p53, bcl-2, MIB1, erbB2 and factor VIII were also evaluated. Of 22 patients enrolled between March 1999 and January 2002, 21 (mean age 63 years; mean PSA level 61 ng/mL; median biopsy Gleason sum 8) completed the neoadjuvant therapy. The clinical stage was organ-confined in three patients (15%); five (25%) had pelvic lymphadenopathy on computed tomography. The neoadjuvant treatment was well tolerated, with only one grade 2 toxicity (Eastern Cooperative Oncology Group grading). All PSA values decreased by >90% from baseline after hormonal therapy only, and the mean reduction from before to after chemotherapy was statistically significant (P = 0.001). Three patients (15%) had a CR, 16 (80%) had a PR and one (5%), with sarcomatoid tumour, had progression; 19 had non-nerve-sparing RRP and there were no major complications during or after RRP. The pathological assessment showed that one patient (5%) had no tumour (pT0) and six (32%) had a 'substantial' response. The overall rate of organ-confined disease was 58%, vs a mean 8% predicted likelihood from the Kattan nomogram. Five patients (26%) had positive surgical margins and four (21%) had positive lymph nodes. At a median follow-up of 53 months, eight patients (42%) were disease-free. Organ-confined disease (P = 0.022), residual cancer at pathology in < or =10% of the surgical specimen (P = 0.007) and no seminal vesicle invasion (P = 0.001) correlated with disease-free survival. A neoadjuvant chemohormonal regimen before RRP is feasible and active in patients with high-risk prostate cancer. The rate of pathological organ-confined disease was higher than expected and responding patients had an 85% disease-free survival rate at 5 years.

Hormonally Induced Spawning, Embryonic Development, and Larval Rearing of the Southern Temperate Banded Morwong, Cheilodactylus spectabilis

Abstract Banded morwong (Cheilodactylus spectabilis) are of interest for marine finfish aquaculture in temperate southern Australia. To improve their ovulatory response, adult females were implanted during the autumn spawning season with slow‐release pellets containing 0–400 μg luteinizing‐hormone‐releasing hormone analogue (LHRHa)/kg body weight within 24 h of capture from the wild. Compared to the sham control group, animals treated with LHRHa produced significantly more eggs on each day after implantation for the following 7 d (91 ± 39 and 290 ± 38 mL) and a higher proportion ovulated (8/12 and 27/27). Of fish treated with LHRHa, 93% ovulated 2 d after implantation and 79% ovulated three times at 2‐d intervals, whereas control animals showed no cyclicity of ovulation and few ovulated more than once. Egg production was highest at the first ovulation after LHRHa treatment and declined at subsequent ovulations. In a second experiment investigating the range 100–400 μg LHRHa, there was no effect of dose rate on ovulation parameters, which additionally examined implantation either immediately after capture or after a 5‐d delay. Compared to immediate implantation, a delay resulted in a lower proportion of animals that could be stripped after implantation (100 and 50%, respectively) and the volume of eggs was lower (135 ± 15 and 107 ± 10 mL). The egg quality was poor following delayed implantation, resulting in no fertilization after artificial insemination compared with immediate implantation in which fertilization and hatch rates were higher for eggs collected on Day 2 after implantation (79 ± 8% and 58 ± 9%) than on Day 4 (23 ± 7% and 15 ± 6%). Thus, it is important to implant animals as soon as possible after capture to ensure optimum egg quality. Good‐quality eggs were buoyant and spherical and had a diameter of 1050 ± 25 μm with a single pigmented oil droplet of 190 ± 9 μm. When a separate large batch of eggs collected 2 d after implantation with 100 μg LHRHa was inseminated and cultured at 18 C, larvae hatched after 63 ± 2 h at a standard length of 2.6 ± 0.4 mm. Newly hatched larvae were buoyant and transparent with only a few melanophores, eyes were nonpigmented and jaws were nonfunctional. By the fourth day, jaws were functional and eyes were fully pigmented. Utilization of the endogenous yolk and oil was completed by Day 6, and swimming commenced with exogenous feeding. Larvae, initially fed lipid‐enriched rotifers followed by Artemia, reached 8.9 ± 0.7 mm length on Day 55, after which they metamorphosed to the postlarval paperfish stage of development, 22 ± 0.9 mm on Day 100, and 43 ± 1.0 mm at 6 mo of age. The results show that treatment of wild‐caught females with slow‐release pellets containing LHRHa is effective for the production of eggs for hatchery rearing.

Recovery of serum testosterone after neoadjuvant androgen deprivation therapy and radical radiotherapy in localized prostate cancer

To prospectively evaluate the time-course of recovery of serum testosterone levels after a short course of luteinizing hormone-releasing hormone analogue (LHRHa) and radical radiotherapy to the prostate. Testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were sequentially measured prospectively in 59 men who received short-course LHRHa treatment and radiotherapy for localized prostate cancer. Measurements were made before treatment (baseline), during LHRHa treatment, and at 6, 12, 18, 24 and >40 weeks after the last LHRHa injection. The median (range) time from the first to last LHRHa injection was 116 (54-194) days. The mean (95% confidence interval) testosterone levels (in nmol/L) at baseline, during treatment and at 6, 12, 18, 24 and >40 weeks afterward were 12.0 (10.8-13.1), 0.6 (0.5-0.7), 1.4 (0.6-2.2), 11.4 (9.7-13), 12.2 (10.5-14), 10.4 (8.9-12) and 11.7 (10.5-13). Four men had low baseline testosterone levels (<6.1 nmol/L). At 6 weeks after the last LHRHa injection, no men had testosterone levels in the 'normal' range; 35% were in the normal range at 12 weeks, 85% at 18 weeks, 89% at 24 weeks, and 96% at 1 year. After LHRHa treatment and radiotherapy, the testosterone levels of most men had recovered to normal by 18-24 weeks after the last LHRHa injection.

Immunohistochemical demonstration of gonadotropin-releasing hormone receptors in prostate carcinoma

The antiandrogen and gonadotropin-releasing hormone (Gn-RH) analogue treatment of prostate carcinoma is based on decreased proliferative and increased apoptotic activity of tumor cells, induced by androgen ablation. Gn-RH analogues decrease the serum level of androgens by breaking the pituitary-gonadal axis, but increasing evidence points to the direct effect of Gn-RH analogues on tumor cells. Immunohistochemical demonstration of Gn-RH receptors recently became possible. Cryostat and paraffin sections of prostate biopsy samples of 10 untreated patients with prostate carcinoma (T2−T3, Gleason score 5−8) were investigated for Gn-RH receptors (Gn-RHR) and androgen receptors, respectively, using the immunoperoxidase method. Membrane bound, focal Gn-RHR positivity was found in 5 samples. Nuclear androgen receptor positivity appeared in 7 samples. No correlation between Gn-RHR and androgen receptor positivity was found, neither receptor status and tumor-nodes-metastasis stage nor Gleason score could be related to each other. Correlation between Gn-RHR positivity and response to luteinizing hormone-releasing hormone analogue treatment will be investigated further.

Broodstock Rearing and Controlled Reproduction of Reeves Shad Tenualosa reevesii

AbstractReeves shad Tenualosa reevesii is one of China's best known anadromous fish, but is presently on the verge of extinction. There is an urgent need for conservation of this species through artificial reproduction and culture. In this study, shad broodstock were held in captivity then were induced to spawn with serial injections of luteinizing hormone‐releasing hormone analogue (LHRHa) following GtH priming by implantations of 17‐methytestosterone (T) combined with environmental manipulations. Induced maturation of 4, 5, and 6‐year‐old females reached 83.3%, 87.5%, and 100%, respectively, while fish in control treatments remained immature. During the gonadal development priming period, mean serum 17‐estradiol levels in the T treatment were significantly higher than the LHRHa treatment and control fish. Gonadal development of females was suppressed when their mesenteric fat index was below 1.5% by April. The effective accumulating temperatures for female and male maturation were 3,995 ± 31.4 C/d and 2,278 ± 8.9 C/d, respectively. Two injections of LHRHa in combination with domperidone (DOM) and environmental regulations were effective in inducing ovulation. About 800,000 fertilized ova were obtained (fertilization 75%) in 1995, and 5,000 fry were hatched in 1996. These results are an important step to develop shad culture and save this endangered species.

Is the flare phenomenon clinically significant?

Objectives: The existing luteinizing hormone–releasing hormone (LHRH) analogs have been the preferred method of inducing androgen deprivation for prostate cancer for over a decade. These agents are well known to cause a surge in serum testosterone levels during the first week of therapy. However, there are wide discrepancies in reports of the frequency and severity of acute clinical progression or clinical flare that might result from the testosterone surge. Also, there is not a clear consensus as to whether antiandrogens should be routinely given to all patients during the first month of LHRH therapy to prevent flare responses. Methods: Clinical trials involving LHRH analog therapy for prostate cancer were reviewed, and the frequency of clinical flare responses noted. Particular attention was given to the kinds of clinical problems associated with the flare response. The use of LHRH analog therapy in treatment of patients with prostate cancer for indications other than overt metastatic disease is discussed, because this is becoming a much more common use of these agents. This article analyzes 2 placebo-controlled, double-blind trials testing the effectiveness of existing antiandrogens in ameliorating flare responses. Results: The use of LHRH analogs for patients with stage D2 disease can be associated with clinical flare in approximately 10% of D2 patients. In addition to bone pain, cord compression, and bladder outlet obstruction, another potentially severe side effect is cardiovascular risk arising presumably from hypercoagulability associated with a rapid increase in tumor burden. In clinical series involving D2 patients, the frequency of clinical flare greatly varies, probably because of the level of scrutiny of the investigator and/or the prostate-cancer tumor burden present at the initiation of therapy. Concomitant antiandrogen therapy reduces, but does not totally eliminate, the flare responses in patients at high risk for flare. Treating prostate cancer in the D0 stage or in the neoadjuvant setting will result in biochemical evidence of testosterone surge, but these patients are at very little risk for clinical flare responses. Conclusions: There is a wide variation in the reported frequency of clinical flare responses from LHRH analogs during the initial treatment of patients with stage D2 disease. The risk-to-benefit ratio, especially in patients with symptomatic bone metastasis, would dictate routine use of antiandrogen therapy for the first month of LHRH analog treatment. For patients at risk for cord compression, other means of ablating testosterone might be considered, such as ketoconazole, orchiectomy, or LHRH antagonists. Clinical flare responses, as opposed to biochemical flare responses, are very rare during LHRH analog therapy for stage D0 disease and/or in the setting of neoadjuvant hormonal therapy.

Longstanding survival without cancer progression in a patient affected by endometrial carcinoma treated primarily with leuprolide

We report here a case of a patient affected by endometrial cancer and treated primarily with leuprolide, the surgical approach being unfeasible due to her compromised conditions. The therapy was continued for more than 6 years, and no progression of the disease was observed. During this period, some histological and immunohistochemical evaluations of the tumour (morphology, grading, proliferation and apoptotic index, E-cadherin expression) were performed. Furthermore, the expression of m-RNA for luteinizing-hormone releasing hormone (LHRH) receptors was determined. The results showed a discrepancy between some biological parameters of the tumour and its clinical characteristics. In fact, despite features suggestive of a progression of the cancer (such as the increase of both tumour grading and proliferating capacity (MIB-1), and a fall in the reparative process (appearance of mutated p53, reduced expression of both bcl-2 and c-erb-2) being detected, neither local invasion nor metastatic lesions were clinically observed. This discrepancy might be due to the maintenance of high levels of E-cadhezin. Moreover, since this tumour was shown to express mRNA for LHRH receptors, new evidence is provided about the favourable impact of LHRH analogue treatment in patients affected by endometrial cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com

Effects of androgen deprivation on prostatic morphology and vascular permeability evaluated with mr imaging.

To assess magnetic resonance (MR) measures of vascular permeability of prostate cancer treated with androgen deprivation and to correlate these with morphologic appearances and serum prostate-specific antigen (PSA) levels. MR examinations in 56 consecutive patients with prostate cancer were performed before and after luteinizing hormone-releasing hormone analog treatment. T2-weighted and contrast medium-enhanced T1-weighted MR images were obtained. Pre- and posttreatment comparisons of morphologic features, glandular volume, and enhancement-related parameters (capillary permeability, leakage space, gadolinium accumulation) were made. Fifty-five tumors were seen before treatment; 42, after treatment. Signal intensity in the peripheral zone and seminal vesicles decreased on T2-weighted images in 42 (75%) and 25 (45%) patients, respectively. Median volume in tumor decreased by 65% (95% CI: 55%, 76%); in central gland, by 30% (95% CI: 25%, 35%). Reductions in tumor permeability (P <.001) and changes in washout patterns were observed (P <.001). Tumor permeability reductions coincided with a decrease in serum PSA levels in 91% of patients. A weak correlation between tumor permeability and volume change was seen (r = 0.55, P =.04). Reductions in peripheral zone (P <.001) and central gland (P =.009) permeability were noted. Androgen deprivation decreases tumor volume and vascular permeability and impairs detection of prostate cancers. Use of MR estimates of permeability may be an additional way of assessing prostatic tumor response to antiandrogen treatment.

Miomectomía histeroscópica. Valoración del tratamiento previo con agonistas LHRH

ObjectiveTo evaluate the utility of prior treatment with luteinizing hormone-releasing hormone (LHRH) we performed a prospective study of 62 hysteroscopic myomectomies Material and methodSixty one myomectomies were performed in 50 patients between January 1995 and December 1998. The patients were divided into two homogeneous groups according to whether they had received prior treatment with analogues. The drug was administered in alternate years. A follow-up protocol was carried out in the gynecology outpatient department ResultsThe mean number of myomas detected was 1.12 ± 0.07. Mean size was 26.16 ± 14.9 mm. The majority (27 (54%)) were type I (Wamsteker). Treatment was successful in 46 patients (92%) and was unsuccessful in 4 (8%). Of these 4 patients, the techniques was incorrectly indicated in 3 (polimyomatous uterus). There were not intraoperative complications. One patient developed postoperative complications (urinary infection). Length of hospital stay after surgery was 1 day. Comparison between groups revealed no significant differences in the technical data or in most of the clinical symptomatology ConclusionHysteroscopic myomectomy is an effective treatment method. The rate of cure is high and morbidity is low. In our experience, the routine use of LHRH analogue treatment before surgery provided no significant benefits. It did not improve the clinical results but did increase the cost of the process. Nevertheless, its selective use in certain cases cannot be excluded

How long should we treat porphyric patients?

Journal Article How long should we treat porphyric patients? Get access I Yamamori I Yamamori Department of Internal Medicine, The Japanese Red Cross Nagoya First Hospital, 3–35 Michishita-cho, Nakamura-ku, Nagoya 453–8511, Japan Correspondence should be addressed to Ikuo Yamamori; Email: yamamori@nagoya-1st.jrc.or.jp Search for other works by this author on: Oxford Academic Google Scholar European Journal of Endocrinology, Volume 142, Issue 2, February 2000, Page 208, https://doi.org/10.1530/eje.0.1420208 Published: 01 February 2000 Article history Received: 11 October 1999 Accepted: 04 November 1999 Published: 01 February 2000

Tumor cell proliferation in prostate cancer after 3 months of neoadjuvant LHRH analogue treatment is a prognostic marker of recurrence after radical prostatectomy

Objectives. To evaluate tumor cell proliferation in relation to histopathologic regressive changes and failure after radical prostatectomy after a 3-month course of neoadjuvant luteinizing hormone-releasing hormone (LHRH) analogue treatment. Methods. We evaluated slides from 103 radical prostatectomy specimens of the 111 patients participating in a randomized trial of a 3-month course of neoadjuvant LHRH analogue treatment before radical retropubic prostatectomy (n = 50) versus surgery alone (n = 53). The histopathologic regressive changes in the specimens were scored by two pathologists. Sections were stained with the anti-Ki-67 monoclonal antibody MIB-1. The proliferation index (PI) was defined as the proportion of Ki-67-positive cells in a random cell count. The patients were followed up until treatment failure or for a mean of 39 months among those without failure. Results. In the neoadjuvant group, increasing histopathologic regressive changes correlated with a decrease in capsular penetration, positive surgical margins, and tumor cell proliferation but did not correlate with Gleason score in biopsies. Treatment failure was not related to the histopathologic regressive changes. In the neoadjuvant treatment group, progression-free survival was longer in the subgroup of patients with tumors with a PI less than 1.2% compared with those with tumors with a PI greater than 1.2% ( P = 0.02). Multivariate analysis of PI and histopathologic and clinical features showed the PI ( P = 0.002) and the pretreatment serum prostate-specific antigen level ( P = 0.003) to be significant prognostic markers of failure in the neoadjuvant group. Conclusions. Tumor cell proliferation after 3 months of neoadjuvant hormonal treatment is a prognostic marker of failure after radical prostatectomy without correlation to Gleason score or the histopathologic regressive changes resulting from hormonal treatment.

Relationship of Serum Testosterone Level with Proliferating Cell Nuclear Antigen and nm23 Protein in Human Prostatic Carcinoma Tissue

To elucidate the biological significance of proliferating cell nuclear antigen (PCNA) and nm23 immunoreactivity in prostatic carcinoma (PC) tissue, both expressions were immunohistochemically analyzed, and the results were compared with the change of the serum testosterone (T) level. The paraffin-embedded materials obtained from 49 untreated PC and 16 hormonally refractory PC (hr-PC) were used. Of the 49 untreated PC, 35 received luteinizing hormone-releasing hormone (LH-RH) analogue treatment, while 14 received a cisplatin-based chemotherapy. The immunohistochemistry of PCNA and nm23 protein was performed using an anti-PCNA monoclonal antibody (PC-10) and an antihuman nm23 polyclonal antibody (OA-11-890), respectively. The serum T level was measured by means of radioimmunoassay. In both untreated PC and hr-PC, the immunoreactivity of nm23 protein significantly correlated with the PCNA expression. Both PCNA expression and nm23 protein immunoreactivity were higher in poorly differentiated PC than those observed in well-differentiated PC, while no significant difference in the serum T level was observed between poorly and well-differentiated PCs. On the other hand, both PCNA expression and nm23 protein immunoreactivity were significantly higher in hr-PC than those observed in untreated PC, whereas the serum T level was significantly lower in hr-PC. In 35 PCs treated with LH-RH analogue, no significant difference in both PCNA expression and nm23 protein immunoreactivity was found between those specimens obtained before and at 3 months after the treatment, while a significant reduction of the serum T level was noted at 3 months after the treatment. Similarly, in 14 PCs treated with a cisplatin-based chemotherapy, the same change of PCNA expression and nm23 protein immunoreactivity as observed in LH-RH analogue treatment was found, while no significant difference of the serum T level was found. These findings appear to indicate that (1) nm23 protein immunoreactivity is interrelated with cellular proliferation in PC tissue and (2) alteration of the serum T level during a short period was not enough to explain the essential change of cellular proliferation of PC tissue, but might reflect other aspects of tumor growth such as apoptosis.

Management of hormonal treatment effects

Androgen ablation is an effective palliative treatment of advanced carcinoma of the prostate. A variety of drugs with diverse mechanisms of action, effectiveness, and side effects are used to treat patients with this disease. This paper discusses the management of the most common side effects that result from treatment with luteinizing hormone-releasing hormone (LHRH) agonists, antiandrogens, ketoconazole, estrogens, and progestational agents. The most common side effects are loss of libido and impotence, hot flushes, gynecomastia, the flare phenomenon (LHRH agonists), nausea and vomiting, liver toxicity, and thromboembolic events (estrogens). The flare phenomenon associated with LHRH analog treatment is prevented best by pretreatment with antiandrogens or estrogens. Progestational agents can reduce hot flashes markedly. Gynecomastia may be prevented by preliminary breast irradiation. Erectile dysfunction is the most problematic side effect and possible treatments for this condition are discussed. Cancer 1995 ;75 : 1983-6.

Growth velocity and serum aminoterminal propeptide of type III procollagen in precocious puberty during gonadotropin‐releasing hormone analogue treatment

Growth velocity and serum aminoterminal propeptide of type III procollagen (P-III-NP) were evaluated in 11 girls (age 3.8-8.5 years) with central precocious puberty during luteinizing hormone releasing hormone (LH-RH) analogue treatment (D-Trp6-LH-RH, 60 micrograms/kg im for 28 days, n = 7; D-ser(TBU)6-LH-RH, 1600 micrograms/day intranasally, n = 4). Before treatment, growth velocity (10.2 +/- 1.9 cm/year) and P-III-NP concentrations (12.8 +/- 4.3 micrograms/l) were in the pubertal range. During therapy, growth velocity significantly decreased to the prepubertal levels. P-III-NP concentrations decreased significantly after six months of therapy (7.9 +/- 3.7 micrograms/l, p < 0.001). Three girls with low growth velocity ( < 4 cm/year), stimulated growth hormone peak < 10 micrograms/l, and altered 12-h nocturnal growth hormone secretion at 12 and/or 18 months of treatment, had a more marked decrease in P-III-NP concentrations (patient 3: -65.9%; patient 5: -58.7%; patient 10: -61.0%) after 6 months of therapy. Our results suggest that LH-RH analogue treatment in central precocious puberty may impair growth. In these cases, measurement of serum P-III-NP levels may be an additional marker to monitor growth.