Short-term Hormone Therapy Research Articles

How the Addition of Hormones Improves Outcome: Hormone Therapy and Radiotherapy

The rationale for the use of neoadjuvant hormone therapy in combination with radiation therapy is that it reduces tumour volume and therefore the amount of radiation therapy that is needed to treat the tumour. To maximise tumour regression, for the first month of NHT at least it is likely that an antiandrogen would also be needed as part of the treatment regimen. It has been found that 3–4 months of hormonal therapy reduces prostate volume by 25–54%. Intermediate-risk patients treated with NHT and concomitant hormonal therapy have been found to have a 94% freedom from biochemical failure after 4 years, suggesting that this group is the ideal patient population to receive short-term hormonal therapy in combination with brachytherapy. For high-risk patients, the conclusions drawn from recent clinical studies suggest that it is necessary to take multimodal approach using a combination of agents. Long-term studies are necessary with radiation therapy to truly determine which patients are failing and how best to manage them.

Hormonal Therapy and Radiotherapy for Localized Prostate Cancer: Who, Where and How Long?

The results from recent randomized trials were used to identify subpopulations of patients most likely to benefit from long versus short-term hormonal therapy with external beam radiotherapy. Radiation Therapy Oncology Group study 9413 included 1,323 men with prostate cancer and a risk of lymph node involvement greater than 15%. In this study the hypotheses tested were that whole pelvis radiotherapy would improve progression-free survival (PFS) compared to prostate only radiotherapy and that neoadjuvant and concurrent hormone therapy (N&CHT) with radiotherapy would improve PFS compared to radiotherapy with adjuvant hormone therapy. The conclusions of this study were compared to other studies using long-term hormonal therapy. At a median followup of almost 5 years, when all 4 treatment arms from study 9413 were compared, the group receiving whole pelvis radiotherapy plus N&CHT had a significant PFS advantage (p = 0.008). Intermediate risk patients should receive N&CHT in combination with external beam radiotherapy while high risk patients require the addition of long-term adjuvant hormone therapy.

Hormone therapy adjuvant to external beam radiotherapy for locally advanced prostate carcinoma: a complication-adjusted number-needed-to-treat analysis.

Hormone therapy commonly is used to treat metastatic, locally advanced, and localized prostate carcinoma. The objective of the current investigation was to determine, using the number-needed-to-treat (NNT) method, the effect of using hormone therapy to treat locally advanced disease, with consideration given to both the complications and the known advantages associated with hormone therapy. A literature review was performed to determine 1) the absolute benefit, based on available clinical endpoints, associated with the addition of hormone therapy to external beam radiotherapy for locally advanced prostate carcinoma; 2) the incidence of side effects of short-term and long-term hormone therapy; and 3) the stepwise progression from biochemical failure to death. A model was constructed to estimate the complication/utility-adjusted survival detriment resulting from the side effects of short-term (</= 6 months) and long-term (> 6 months) hormone therapy, and the absolute/unadjusted and complication-adjusted NNTs for the addition of short-term and long-term hormone therapy were computed. In all cases, the magnitudes and signs of the NNTs obtained were used to gauge the effect of hormone therapy. The unadjusted NNTs were positive and in most cases had relatively small magnitudes (the greater the NNT, the smaller the benefit) for both short-term and long-term hormone therapy; these results were expected, and they suggested that there is a strong benefit associated with the use of hormones adjuvant to radiotherapy for locally advanced disease. Adjusted NNTs remained positive and had relatively small magnitudes even after the introduction into the analysis of complications of short-term and long-term hormone therapy. This finding, although weak with respect to the effect of short-term hormone therapy on cause-specific survival, remained robust over the range of values for utility impairment expected from short-term and long-term hormone therapy. The benefits of short-term and long-term hormone therapy for locally advanced prostate carcinoma appear to be significant and to outweigh the associated side effects. Long-term therapy appears to be better than short-term therapy in terms of virtually all endpoints studied, even when the increased incidence of side effects is considered. The current investigation was successful in the use of the complication-adjusted NNT method for oncologic and radiotherapeutic scenarios in which the results of randomized trials could be summarized, adjusted for treatment toxicity, and individualized to a given patient.

Effect of short-term hormone therapy on oxidative stress and endothelial function in African American and Caucasian postmenopausal women

Objective In postmenopausal women (PMW), the effect of a short-term course of estrogen/progestin HT on free radical oxidative stress was evaluated. In addition, HT’s effect on plasma nitric oxide (NO) activity was determined as a measure of vascular endothelial function. We investigated the relationship of these markers and HT across race and the cardiovascular risk factors of smoking, diabetes and hypertension. Design A prospective, observational study comparing preintervention and postintervention. Setting Academic research center. Patient(s) Twenty-seven (14 African American and 13 Caucasian) PMW volunteers. Intervention(s) Six weeks of continuous, combined estrogen/progestin HT. Main outcome measure(s) Plasma concentrations of free 8-epi-prostaglandin F 2α (8-isoprostane) before and after HT were compared as a measure of oxidative stress. Nitrite, the stable oxidation metabolite of NO, was measured by the Greiss reaction after nitrate reduction to nitrite with cadmium. Results Plasma levels of free 8-isoprostane decreased significantly after 6 weeks of HT. Although almost all subjects benefited from the reduction in free 8-isoprostane, PMW with at least one cardiovascular risk factor (n = 19) demonstrated higher free 8-isoprostane than did subjects with no risk factors. Plasma levels of nitrite increased after 6 weeks of HT, but the difference was not statistically significant. Caucasian PMW demonstrated a greater increase in plasma levels of nitrite after 6 weeks of HT as compared with African American subjects, who exhibited almost no change. Conclusion(s) Short-term administration of HT significantly reduces oxidative stress in PMW and is consistent across race. However, there was an observed racial difference in endothelial NO response to HT between African American and Caucasian PMW.

Race and Survival of Men Treated for Prostate Cancer on Radiation Therapy Oncology Group Phase III Randomized Trials

We assessed the impact of race on survival in men treated with external beam radiotherapy with or without hormonal therapy for localized prostate cancer in Radiation Therapy Oncology Group randomized trials. Between 1975 and 1992, 2,048 men were treated for clinically localized prostate cancer in 1 of 4 consecutive prospective phase III randomized trials. After excluding nonblack and nonwhite men 2,012 remained for analysis. Patients were included in this analysis if they were deemed evaluable and eligible for the trial, and followup information and centrally reviewed pathological results were available. Short-term hormonal therapy consisted of goserelin acetate and flutamide administered 2 months before and during radiotherapy. Long-term hormonal therapy consisted of adjuvant goserelin acetate, which was generally given for 2 years or more. Pretreatment prostate specific antigen (PSA) findings were available in 430 cases (21%), including 213 treated with radiotherapy alone, 60 treated with short-term hormonal therapy and 157 on long-term hormonal therapy. Mean pretreatment PSA was 68.8 and 35.2 ng./ml. in black and white patients, respectively. Cox proportional hazards models were used to identify the impact of previously defined risk groups on overall and disease specific survival. Multivariate analysis was done for the significance of race using a stratified Cox model. Median followup in patients treated in early and late studies exceeded 11 and 6 years, respectively. On univariate analysis black race was associated with lower overall and disease specific survival (p = 0.04, RR = 1.24 and p = 0.016, RR = 1.41, respectively). After adjusting for risk group and treatment type (with or without short-term or long-term hormonal therapy) race was no longer associated with outcome (p >0.05). The trend for a persistent difference in survival was likely due to the higher tumor burden in black men, as reflected in higher PSA. As previously reported, tumor grade (Gleason score), palpation T stage, lymph node status, pretreatment PSA and treatment type are major predictors of overall and disease specific survival. We noted no evidence that race has independent prognostic significance in patients treated for prostate cancer in Radiation Therapy Oncology Group prospective randomized trials.

Is long term hormonal therapy needed with dose escalation in high risk prostate cancer? Results of treatment with 9 months of hormonal therapy, brachytherapy and 3D conformal external beam irradiation

Purpose: Recent trials have shown that long-term (2 years) hormonal therapy (HT) is superior to short term hormonal therapy in high risk prostate cancer when standard doses of external beam radiation therapy (EBRT) are delivered. The need for long-term HT when dose escalation is used is not known. To address this issue, PSA failure rates following a regimen of 9 months of HT, and dose escalation with brachytherapy and 3D conformal EBRT were calculated to determine the efficacy of this treatment and to see if there exits a subgroup of high risk patients whose outcomes were suboptimal and who might benefit from long-term HT.

A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease.

Most primary prevention studies have found that long-term users of postmenopausal hormone therapy are at lower risk for coronary events, but numerous questions remain. An adverse influence of hormone therapy on cardiovascular risk has been suggested during the initial year of use; however, few data are available on short-term hormone therapy. In addition, the cardiovascular effects of daily doses of oral conjugated estrogen lower than 0.625 mg are unknown, and few studies have examined estrogen plus progestin in this regard. To investigate duration, dose, and type of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Prospective, observational cohort study. Nurses' Health Study, with follow-up from 1976 to 1996. 70 533 postmenopausal women, in whom 1258 major coronary events (nonfatal myocardial infarction or fatal coronary disease) and 767 strokes were identified. Details of postmenopausal hormone use were ascertained by using biennial questionnaires. Cardiovascular disease was established by using a questionnaire and was confirmed by medical record review. Logistic regression models were used to calculate relative risks and 95% CIs, adjusted for confounders. When all cardiovascular risk factors were considered, the risk for major coronary events was lower among current users of hormone therapy, including short-term users, compared with never-users (relative risk, 0.61 [95% CI, 0.52 to 0.71]). Among women taking oral conjugated estrogen, the risk for coronary events was similarly reduced in those currently taking 0.625 mg daily (relative risk, 0.54 [CI, 0.44 to 0.67]) and those taking 0.3 mg daily (relative risk, 0.58 [CI, 0. 37 to 0.92]) compared with never-users. However, the risk for stroke was statistically significantly increased among women taking 0.625 mg or more of oral conjugated estrogen daily (relative risk, 1.35 [CI, 1.08 to 1.68] for 0.625 mg/d and 1.63 [CI, 1.18 to 2.26] for >/=1.25 mg/d) and those taking estrogen plus progestin (relative risk, 1.45 [CI, 1.10 to 1.92]). Overall, little relation was observed between combination hormone therapy and risk for cardiovascular disease (major coronary heart disease plus stroke) (relative risk, 0.91 [CI, 0.75 to 1.11]). Postmenopausal hormone use appears to decrease risk for major coronary events in women without previous heart disease. Furthermore, 0.3 mg of oral conjugated estrogen daily is associated with a reduction similar to that seen with the standard dose of 0.625 mg. However, estrogen at daily doses of 0.625 mg or greater and in combination with progestin may increase risk for stroke.

Predicting long-term survival, and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials

Purpose: To assess the impact of short-term and long-term androgen suppression on the disease-specific and overall survival of 2200 men treated with radiotherapy on one of 5 prospective randomized trials when stratified by prognostic risk groups. Methods and Materials: Between 1975 and 1992, 2742 men were treated for clinically localized prostate cancer on one of 5 consecutive prospective Phase III randomized trials. Patients were selected for this analysis if they were deemed evaluable and eligible for the trial, and if follow-up information was available. For this analysis patients were stratified into four previously described prognostic risk groups: Group 1 patients had a Gleason score (GS) = 2–6, and T1–2Nx; Group 2: GS = 2–6, T3Nx; or GS = 2–6, N+, or GS = 7, T1–2Nx; Group 3: T3Nx, GS = 7; or N+, GS = 7, or T1–2Nx, GS = 8–10; and Group 4 patients were T3Nx, GS = 8–10, or N+, GS = 8–10. The median pretreatment prostate-specific antigen (PSA) was 25 ng/ml for the 434 evaluable patients for whom this information was available. The median follow-up times for patients treated on early studies exceeded 11 years, and for more recent studies 6 years. Results: Risk group 2 patients with “bulky” or T3 disease appeared to have a disease-specific survival benefit at 8 years with the addition of 4 months of goserelin and flutamide. Group 3 and 4 patients were noted to have an approximately 20% higher survival at 8 years with the addition of long-term hormonal therapy ( p ≤ 0.0004). Conclusions: Based on this meta-analysis of RTOG trials, subsets of patients can be identified who either do not appear to benefit from the use of hormonal therapy, benefit from short-term hormonal therapy, or who benefit only from long-term hormonal therapy. These observations should be confirmed by prospective randomized trials before they can be considered conclusive. In the meantime, however, these observations provide rational guidelines for deciding who should receive hormonal therapy and for how long.

Short-Term Hormonal Replacement Therapy in Postmenopausal Women: Effect on Weight, Caloric Intake, and Metabolic Parameters

LEARNING OBJECTIVE: To determine whether institution of hormonal replacement therapy is associated with alterations in weight. A common perception among postmenopausal women (PMW) is that hormonal replacement therapy (HRT) causes weight gain. Healthy PMW aged 45-55 years (n=9) arid 70-80 years (n=7) were enrolled. Subjects were studied at baseline, after 1 month of estrogen (estraderm 50 mcg) followed by a further month of estrogen at the same dose with progesterone (100 mg per vagina bid) for the final 7 days. Food and activity questionnaires, anthropometric measures, and indirect calorimetry were performed at each visit. Fat mass was estimated by bioimpedance and by skinfold measurements. These parameters were compared across the 3 visits using paired t-test. Serum estradiol level increased from 22.1±1 pg/ml to 80.4±11 pg/ml, while progesterone increased from 0.6 ng/ml to 11.9±2 ng/ml after replacement. No significant change in weight across the 3 visits was observed in the group as a whole (66.1-66.5-66.6 kg) or in the older PMW (68.8-68.9-68.6 kg); however when the young were considered separately there was a significant but small increase after 2 months of HRT (64.0-64.7-65.1 kg, p<0.05 between visits 1 and 3). Mean BMI, caloric intake, and activity level were unchanged in either group. Basal and measured resting energy expenditure remained unchanged, % body fat was stable as assessed by skinfolds and bioimpedance as well as the total body water (TBW) in both groups. There was no effect of short-term HRT on body weight in older postmenopausal women, however there was a significant, but small (1.1±0.5 kg) increase in young postmenopausal women, a change that was too small to be reflected in changes in BMI. Thus, short-term HRT is not associated with appreciable changes in body weight in normal women.

A clinical and pathological study of radical prostatectomy for prostate cancer

Thirty-one patients with prostate cancer underwent radical prostatectomy and simultaneous pelvic lymphadenectomy at Matsumoto National Hospital between 1988 and 1994. Prognostic factors are discussed from their clincopathological findings. The patients ranged from 54 to 80-year-old, with an average age of 69.9 years. The median follow-up period was 44 months. The diagnosis was confirmed by needle biopsy or transurethral resection of the prostate. All the patients received short-term endocrine therapy preoperatively, and only noncuratively resected patients underwent adjuvant therapy postoperatively. At initial diagnosis, the tumor grades were well, moderately, and poorly differentiated adenocarcinoma in 9, 12, and 10 patients, respectively. The clinical stage was defined as A2, B, C, D1, and D2 in 12, 4, 6, 3, and 6 patients, respectively. A difference of tumor grade was found between the initial diagnosis and the final diagnosis based on the resected prostate in 8 patients (26%), with 7 of them (88%) showing an increase in grade in the final diagnosis. Also revealed was that 11 of the 25 patients (44%) in stage A2, B, C, or D1 had been understaged preoperatively. The five-year actuarial survival rates were 100%, 92%, and 51% for patients with well, moderately, and poorly differentiated adenocarcinoma, respectively, with a significant difference noted between well and poorly differentiated adenocarcinoma (p = 0.03). Recurrence only developed in patients with pathological stage D tumors. However, the presence or absence of lymph node metastasis did not affect the crude 5-year survival rate. Several stage D patients were successfully treated by radical prostatectomy and adjuvant therapy, achieving long survival. These results indicate that patients in clinical stage C have tumors which exhibit differing biological behavior. These patients should be analyzed and classified more precisely so that the most appropriate therapy can be chosen.

Orthopedic aspects of skeletal dysplasia in children.

Significant advances in the management of skeletal dysplasia have occurred during the past year. A revision of the Paris classification of constitutional disorders of bone has been proposed. New mutations have been identified in several disorders that confirm genetic heterogeneity within similar phenotypes. New clinical data of growth, fracture rates, and incidence of major skeletal and extraskeletal changes as well as the natural history and treatment of spinal deformities in osteogenesis imperfecta have been reported. Pilot studies of short-term growth hormone therapy in patients with achondroplasia and hypochondroplasia and nasal-osteocalcin therapy in osteogenesis imperfecta patients has been described, but the long-term effectiveness of these treatments remains to be determined. Extensive limb lengthening continues to be an important part of the treatment of patients of short stature in Europe, but complication rates continue to be very high. Both the current and future roles for this type of therapy are highly controversial. The potential for enzyme replacement therapy and retrovirus-mediated gene transfer in a variety of mucopolysaccharidosis disorders has been given new meaning by studies with cultured fibroblasts, which suggest that active enzymes can enter into and be synthesized in abnormal cells resulting in normalization of substrate turnover.

Scanning electron microscopy of the effect of short-term hormonal therapy on postmenopausal endometrium.

A scanning electron microscopic study of the endometrial surface was made in postmenopausal women, both untreated and after short-term hormonal therapy. In the untreated women the endometrial surface was characterized by slightly bulging cell surfaces with few, short microvilli. The surface area of the cells varied. Often a single kinocilium was observed.After administration of estrogen alone the epithelial cells showed a uniform surface area. The cell surfaces were bulging and possessed numerous fairly long microvilli, which often formed tuft-like structures. The length of the microvilli seemed to depend upon the potency of the estrogen used.After sequential administration of estrogen followed by a gestagen, the uterine surface was characterized by microvilli and apical protrusions. The microvilli were long and numerous when the priming estrogen was estradiol + estriol, while they were shorter when estradiol valerate was given. The apical protrusions were larger and more numerous after administration of ...

Short-term hormone therapy; its effect in active rheumatic carditis of varying duration.

IN 1949 when ACTH became available, we considered that we could best evaluate hormone therapy by selecting patients observed at the onset of carditis before irreversible damage was sustained, and that the duration of therapy should be significantly less than the usual duration of this self-limited disease.1 In a previous report of the effect of short-term hormone therapy in 55 patient attacks of active carditis of three to twenty-one days' duration, it was demonstrated that in the majority of patients, early adequate therapy for an average period of seven days resulted in no overt residual cardiac damage. Patients were ambulatory . . .