Luteinizing Hormone-releasing Hormone Therapy Research Articles

Effectiveness of surgical castration by bilateral subcapsular orchiectomy as monotherapy for the treatment of advanced prostate cancer.

Prostate cancer is the most common malignancy in men and the second cause of death due to cancer [1]. Treatment of prostate cancer has been a field of many progresses, but the discovery of the role of androgen in the genesis of prostate cancer by Hugins and Hodges is really a milestone in the treatment of advanced prostate cancer [2]. In patients with advanced prostate cancer, options for androgen ablation include bilateral orchiectomy, therapy with luteinizing hormone-releasing hormone (LHRH) analogues and antagonists, and combined androgen blockade (typically a LHRH analogue plus a first-generation anti-androgen). Although orchiectomy remains the historical gold standard for androgen ablation, LHRH therapy is considered to be equivalent therapeutically. Medical castration has the advantage to induce less psychological effects comparatively to the surgery, reason why in developed countries patients are managed with medical therapy [3]. However, LHRH agonists cannot induce a complete castration levels of testosterone in some patients [4]. Instead, surgical castration can completely eliminate remaining testosterone produced by the Leydig cells in testes [5]. According to the latest recommendations of the European Association of Urology (EAU), androgen deprivation therapy (ADT) is the firstline indication in patients with advanced and metastatic PCa [6]. This first line is made of LHRH agonists, surgical castration representing the second line [7] And Several techniques of surgical castration have been described with comparable results in terms of patient survival and quality of life, but the sub-capsular technique of preserving testicular albuginea and epididymis is the most commonly used [8]. The relatively high cost of chemical castration is a constraint in the therapeutic choice in developing countries [9]. Therefore, surgical castration is an interesting alternative because of its simplicity and affordability in patients, most of whom have no health insurance. In Togo, most patients diagnosed with prostate cancer are at the metastasis stage, and surgical castration is often used as first-line treatment [10]. The aim of this study was to assess the biological and clinical effectiveness of surgical castration as the sole treatment in patients with advanced prostate cancer.

6-month Formulations of Androgen Deprivation Therapy for Advanced Prostate Cancer: Effectiveness and Rationale for Extended Dosing

Background: Luteinizing hormone-releasing hormone (LHRH) agonists and GnRH antagonists are the most widely used androgen deprivation therapy to achieve castration levels of serum testosterone (T). Adherence to dosing schedules is important to avoid treatment failure. A recent analysis found a high non-adherence rate of 84% for LHRH agonist injections based on dosing schedules used in pivotal trials. Method: Narrative review of LHRH therapy and evaluation of which offers optimal efficacy, safety, and practicality. Results: 6-month LHRH agonist formulations require fewer appointments for injections than shorter-acting formulations. Therefore, the frequency of late/missed doses and overall non-adherence may be reduced compared to options requiring frequent dosing (e.g., oral therapies and shorter-acting injections). This flexibility may be preferable for patients who live in multiple locations throughout the year, live long distances from clinics, and/or lack access to reliable transportation. 6-month formulations may also have cost benefits compared to shorter-acting doses. Despite similar levels of T suppression during the labeled dosing period, individual 6-month LHRH agonist formulations appear to have unique profiles, e.g., 6-month subcutaneous leuprolide acetate (LA) results in lower T escape rates compared to 6-month intramuscular LA, if dosing is late. Conclusion: The efficacy and practicality offered by 6-month LHRH formulations suggest these could reduce opportunities for late injections by requiring fewer office visits and provide greater confidence that efficacy will be maintained should there be extenuating circumstances leading to delays in therapy administration, as experienced during the recent pandemic.

Abiraterone acetate plus LHRH therapy versus abiraterone acetate while sparing LHRH therapy in patients with progressive, metastatic and chemotherapy-na\xefve, castration-resistant prostate cancer (SPARE): study protocol for a randomized controlled trial

BackgroundThe value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Argumentation for cessation of LHRH therapy is the prolonged suppression of testosterone levels after the withdrawal of LHRH analogues and the fact that disease progression occurs despite castration levels of testosterone. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase (Cyp17)-inhibitor, abiraterone, which has the ability to further suppress testosterone serum levels over LHRH therapy alone, continuation of LHRH therapy seems to be negligible. However, the proven increase of luteinizing hormone levels after LHRH withdrawal, which is even further increased by abiraterone, may counteract the effects of abiraterone by the induction of enzymes of steroidogenesis. Therefore, cessation of LHRH therapy when starting treatment with abiraterone in CRPC may display an unpredictable hazard to the patients. This study will explore the role of continuation of LHRH therapy when starting treatment with abiraterone in patients with asymptomatic or mildly symptomatic, chemotherapy-naïve CPRC.Methods/designThe trial will assess radiographic progression-free survival after 12 months of treatment with abiraterone/prednisone in patients who will be randomized to receive continuing LHRH therapy versus LHRH withdrawal at the time of starting abiraterone therapy.DiscussionThis multicenter, prospective, randomized, exploratory phase-II trial will bring about new data regarding the efficacy and safety of abiraterone/prednisone treatment with or without continuation of LHRH therapy. In addition, further insight into the complex hormonal changes under treatment will be gained and the results of this trial may give rise to a larger phase-III trial to examine the possibility of withdrawing LHRH therapy in patients with CRPC.Trial registrationClinicalTrials.gov, ID: NCT02077634. Registered on 9 December 2013.

A systematic review and meta-analysis of comparative studies assessing the efficacy of luteinizing hormone-releasing hormone therapy for children with cryptorchidism.

To assess the efficacy of intranasal luteinizing hormone-releasing hormone (LHRH) therapy for cryptorchidism. Eligible studies were identified by two reviewers using PubMed, Embase, and Web of Science databases. Primary outcomes were complete testicular descent rate, complete testicular descent rate for nonpalpable testis, and pre-scrotal and inguinal testis. Secondary outcomes included testicular descent with different medicines strategy and a subgroup analysis. Pooled data including the 1255 undescended testes showed that complete testicular descent rate was 20.9 % in LHRH group versus 5.6 % in the placebo group, which was significantly different [relative risk (RR) 3.94, 95 % confidence interval (CI) 2.14-7.28, P < 0.0001]. There was also a significant difference in the incidence of pre-scrotal and inguinal position testis descent, with 22.8 % in the LHRH group versus 3.6 % in the placebo group (RR 5.79, 95 % CI 2.94-11.39, P < 0.00001). However, side effects were more frequent in the LHRH group (RR 2.61, 95 % CI 1.52-4.49, P = 0.0005). There were no significant differences for nonpalpable testes. LHRH had significant benefits on testicular descent, particularly for inguinal and pre-scrotal testes, which was also accompanied by temporary slight side effects.

Efficacy of degarelix in prostate cancer patients following failure on luteinizing hormone-releasing hormone agonist treatment: results from an open-label, multicentre, uncontrolled, phase II trial (CS27).

To evaluate the efficacy of second-line degarelix in patients with prostate cancer (PCa) after treatment failure with a luteinizing hormone-releasing hormone (LHRH) agonist. This 1-year exploratory, multicentre, open-label phase II trial was performed in 2 patient cohorts (Cohort 1, n = 25; Cohort 2, n = 12) in Germany. Patients with castrate-resistant PCa after primary hormonal treatment received degarelix 240 mg, followed by 11 monthly maintenance doses of 80 mg. The primary endpoint was the proportion of patients with decreasing/stable prostate-specific antigen (PSA) (relative change ⩽+10% of baseline PSA) after 3 months. At Month 3, the response rate (intention-to-treat, last observation carried forward analysis) was 16.7% [95% confidence interval (CI): 4.74-37.38] in Cohort 1 and 33.3% (95% CI: 9.92-65.11) in Cohort 2. The probability of completing 12 months without PSA progression was 8.8% (95% CI: 1.51-24.3) in Cohort 1 and 8.3% (95% CI: 0.5-31.1) in Cohort 2. Degarelix was well tolerated; the most frequently reported adverse events were local injection-site reactions. In PCa patients who failed LHRH therapy, degarelix was well tolerated and achieved a limited PSA response. Phase III trials show that disease control benefits with degarelix versus agonists are more clearly demonstrated as first-line therapy.

Editorial

With growing interest for screening, early detection and newer treatment options for prostate cancer, one may have the impression that benign prostatic hyperplasia (BPH) is a declining academic and clinical topic in our everyday practice. However, if one studies the demographics of the population across the world, aging stands out to be one of the most prominent health issues and cost makers. Symptoms related to BPH and bladder outlet obstruction (BOO) represent, therefore, a growing healthcare issue that needs further analysis, innovation and time adapted treatment and strategy. This section in Current Opinion in Urology summarizes the current research, recommendations and investigations of some of the finest leaders, including a nobel price laureate among others. From diagnosis to treatment, this issue covers indeed the newest trends. Bostanci et al. (pp. 5–10) review the correlation between inflammation and BPH and eventual consequences. Abdi et al. (pp. 11–16) summarize the current application of standard and new imaging techniques for patients with lower urinary tract symptoms due to BOO and BPH. Rick and Schally (pp. 17–24) reflect the view of an outstanding team of researchers around Dr Schally, a nobel price laureate, the ‘father’ of luteinizing hormone-releasing hormone therapy for prostate cancer. They report and investigate the role of hormonal manipulation in the pathophysiology but moreover in the treatment of BPH today. Lusuardi and Janetschek (pp. 25–29) review new emerging technologies for BPH. Marien and Shah (pp. 30–37) investigate BPH treatment options in the case of anticoagulation therapy, a growing source of concern in our everyday practice. Finally, Espinosa (pp. 38–41) covers an extremely attractive topic, namely, ‘The role of nutrition in treating patients with symptoms related to BOO and BPH’. Acknowledgements None. Conflicts of interest There are no conflicts of interest.

Incomplete testosterone suppression with luteinizing hormone‐releasing hormone agonists: does it happen and does it matter?

What's known on the subject? and What does the study add? Previous reports, with small numbers of patients, have described the problem of incomplete testosterone suppression (>1.1 or 1.7 nmol/L) with LHRH agonists. Various predisposing factors have been suggested: different drug agents and patient factors such as age, pretreatment testosterone levels and weight. Such incomplete testosterone suppression has been shown in one small report to be associated with increased PSA failure rates and in another report in those with metastases, with worse survival. This study used testosterone assays that are more accurate at low levels than those used in most previous reports in a large dataset of 2196 men, and confirmed incomplete testosterone suppression (breakthrough) rates >1.7 nmol/L of 3.4% and >1.1 nmol/L of 6.6%. We showed that younger age was strongly associated with the risk of breakthrough, with a minor effect of increasing body mass index. Repeated breakthroughs were more common (16%) in those who had already had one breakthrough. Interim measures of cancer control (PSA kinetics during LHRH therapy) were inferior in those with a breakthrough, and those with breakthroughs between 1.1 and 1.7 nmol/L had worse long-term biochemical control rates. • To describe breakthrough rates above castrate levels of testosterone, in a population-based series of men undergoing adjuvant luteinizing hormone-releasing hormone (LHRH) agonist therapy with curative radiation therapy. • To explore the predisposing factors for such breakthroughs and their impact on subsequent outcomes. • All men treated for prostate cancer between 1998 and 2007 with curative radiation in the province of British Columbia, Canada were potentially eligible (n= 11752). Of these, 2196 fulfilled the eligibility criteria. • Serial testosterone measurements were obtained during continuous LHRH therapy. • Breakthrough rates >1.1 nmol/L and >1.7 nmol/L were calculated for each LHRH injection and for each patient course. • Predisposing factors were identified, and early surrogates of oncological outcome (neoadjuvant nadir and post-treatment nadir) were determined. • The risk of a breakthrough >1.1 nmol/L was 6.6%, and >1.7 nmol/L was 3.4% per patient course and 5.4% and 2.2% per LHRH injection (inclusive ranges). • Repeated breakthroughs occurred in 16% of patients. • Younger men were more liable to breakthroughs (P < 0.001). • Early PSA kinetic surrogates of cancer control were inferior in those with breakthroughs. • Neither overall biochemical non-evidence of disease (bNED) nor survival were compromised, although subgroup analysis showed inferior 5-year bNED in those with breakthroughs of 1.1-1.7 nmol/L vs those without (58% vs 73%, respectively; P= 0.048). • Breakthroughs with LHRH agonists occur occasionally per injection, but occur commonly per patient course of treatment, and adversely affect early surrogate measures of outcome. • The monitoring of testosterone levels during therapy is therefore advised.

Long-term, pulsatile, low dose, subcutaneous luteinizing hormone-releasing hormone administration in men with idiopathic oligozoospermia. Failure of therapeutic and hormonal response.

In four normal men with a history of long standing infertility, severely disturbed sperm qualities (determined in at least three spermiograms), normal serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels (measured over a time period of 90 minutes), and lack of evidence of further andrological or other obvious endocrine disorders the effectiveness of luteinizing hormone-releasing hormone (LH-RH) treatment was investigated. LH-RH was administered subcutaneously with a portable, comterized infusion pump (Zyclomat) for 3 months, with administration intervals of 90 minutes and bolus dosages of 5 micrograms (three patients) and 20 micrograms (one patient). Semen qualities during and after LH-RH treatment, as compared to pretreatment values, showed no improvement in volume of ejaculate, number of sperms per milliliter and motility. During or at the end of the treatment period no evident differences were observed in serum LH, FSH and testosterone levels (measured over a 90 minutes period) compared with hormonal values before LH-RH therapy, nor at the low-dose (5 micrograms) neither at the high-dose (20 micrograms) administration schedule. It is concluded that pulsatile subcutaneous LH-RH treatment in normogonadotropic, oligozoospermic men does not seem to improve the therapeutical arsenal.

Does Neoadjuvant Hormone Therapy for Early Prostate Cancer Affect Cognition? Results From a Pilot Study

OBJECTIVE: To examine, in a prospective study, the influence that temporary reversible medical castration for localized prostate cancer has on cognition, by assessing whether temporary 3-5 month treatment with a luteinizing-hormone releasing hormone (LHRH) agonist before radical radiotherapy had a short- or long-term affect on cognitive function. PATIENTS, SUBJECTS AND METHODS: Thirty-two patients with localized prostate cancer had cognitive assessments at baseline (T1) before the start of drug treatment, at 3 months (T2) or on completing drug treatment but before radiotherapy, and 9 months later (T3). Eighteen men with no prostate cancer (controls subjects) completed the cognitive tests at the same times. In addition, psychological functioning and quality of life were assessed at the same times, together with serum free and bound testosterone, beta-oestradiol and sex hormone-binding globulin levels. RESULTS: There was a significant cognitive decline (on at least one cognitive task) at T2 in 15 (47%) patients vs three (17%) of controls (odds ratio 4.412, P = 0.033). Most patients (nine of 15) who had a change in performance declined on tasks of spatial memory and ability. At T3 there was significant cognitive decline in 11 (34%) patients and five (28%) control subjects (odds ratio 1.37, P = 0.631). CONCLUSION: This pilot study suggests that short-term LHRH therapy for early-stage prostate cancer has modest short-term consequences on men's cognitive functioning; a larger prospective study is warranted.

Does neoadjuvant hormone therapy for early prostate cancer affect cognition? results from a pilot study

OBJECTIVE To examine, in a prospective study, the influence that temporary reversible medical castration for localized prostate cancer has on cognition, by assessing whether temporary 3–5 month treatment with a luteinizing-hormone releasing hormone (LHRH) agonist before radical radiotherapy had a short- or long-term affect on cognitive function. PATIENTS, SUBJECTS AND METHODS Thirty-two patients with localized prostate cancer had cognitive assessments at baseline (T1) before the start of drug treatment, at 3 months (T2) or on completing drug treatment but before radiotherapy, and 9 months later (T3). Eighteen men with no prostate cancer (controls subjects) completed the cognitive tests at the same times. In addition, psychological functioning and quality of life were assessed at the same times, together with serum free and bound testosterone, β-oestradiol and sex hormone-binding globulin levels. RESULTS There was a significant cognitive decline (on at least one cognitive task) at T2 in 15 (47%) patients vs three (17%) of controls (odds ratio 4.412, P = 0.033). Most patients (nine of 15) who had a change in performance declined on tasks of spatial memory and ability. At T3 there was significant cognitive decline in 11 (34%) patients and five (28%) control subjects (odds ratio 1.37, P = 0.631). CONCLUSION This pilot study suggests that short-term LHRH therapy for early-stage prostate cancer has modest short-term consequences on men's cognitive functioning; a larger prospective study is warranted.

PARENTERAL MEDROXYPROGESTERONE FOR THE MANAGEMENT OF LUTEINIZING HORMONE RELEASING HORMONE INDUCED HOT FLASHES IN MEN WITH ADVANCED PROSTATE CANCER

Luteinizing hormone releasing hormone (LHRH) agonist therapy for advanced prostate cancer can manifest significant side effects affecting quality of life, most notably hot flashes. This study evaluated the effectiveness of parenteral medroxyprogesterone acetate (MPA) in reducing the frequency and severity of these hot flashes. A multi-institutional retrospective review of hot flashes from LHRH therapy for prostate cancer was conducted. The hot flashes were quantified and the severity was graded (3-point analogue scale) before and after treatment with MPA. Two doses of MPA (400 or 150 mg intramuscularly) were administered. Statistical analysis (Student's t test) evaluated the quantity of hot flashes, the quality of hot flashes, and dose effectiveness. A total of 48 men (40 at 400 mg, 8 at 150 mg) with a mean age of 71.4 years (range 54 to 87) from 3 institutions were evaluated. There were 91% with symptomatic improvement with MPA, and half (46%) had a complete response defined as total elimination of hot flashes. The median number of the hot flashes per day decreased from 4 to 1 and the median severity score decreased from 2 to 1 (p <0.05). Significance was not achieved comparing the 2 doses. Complete responders were not noted with the 150 mg dose. Anticipated response to MPA did not correlate with the number or severity of the hot flashes. This study is the first multi-institutional evaluation of hot flashes demonstrating significant reduction in quantity and severity with MPA. Based on these data we now manage hot flashes associated with LHRH analogues with 400 mg of MPA.

Does neoadjuvant hormone therapy for early prostate cancer affect cognition? Results from a pilot study

To examine, in a prospective study, the influence that temporary reversible medical castration for localized prostate cancer has on cognition, by assessing whether temporary 3-5 month treatment with a luteinizing-hormone releasing hormone (LHRH) agonist before radical radiotherapy had a short- or long-term affect on cognitive function. Thirty-two patients with localized prostate cancer had cognitive assessments at baseline (T1) before the start of drug treatment, at 3 months (T2) or on completing drug treatment but before radiotherapy, and 9 months later (T3). Eighteen men with no prostate cancer (controls subjects) completed the cognitive tests at the same times. In addition, psychological functioning and quality of life were assessed at the same times, together with serum free and bound testosterone, beta-oestradiol and sex hormone-binding globulin levels. There was a significant cognitive decline (on at least one cognitive task) at T2 in 15 (47%) patients vs three (17%) of controls (odds ratio 4.412, P = 0.033). Most patients (nine of 15) who had a change in performance declined on tasks of spatial memory and ability. At T3 there was significant cognitive decline in 11 (34%) patients and five (28%) control subjects (odds ratio 1.37, P = 0.631). This pilot study suggests that short-term LHRH therapy for early-stage prostate cancer has modest short-term consequences on men's cognitive functioning; a larger prospective study is warranted.

The role of luteinizing hormone-releasing hormone therapy in locally advanced prostate cancer and biochemical failure: considerations for optimal use

Background: More patients are being diagnosedwith prostate cancer at an earlier age with earlier stage disease because of advances in screening and detection. Investigators continue to explore the use of hormone therapy, particularly luteinizing hormone-releasing hormone (LHRH) analogues, earlier in the course of disease. Objective: This review summarizes clinical evidenceregarding the safety and efficacy of LHRH analogues in the treatment of locoregional disease or following biochemical failure. Methods: Relevant information from clinical studieswas identified through a MEDLINE search of the medical literature published in English in the last 5 years (search terms: LHRH and prostate cancer). The search included prospective and retrospective clinical studies on LHRH therapy in locally advanced prostate cancer. Additional relevant publications published before 1999 were identified from citations in the resulting articles. Results: The available clinical evidence suggeststhat the use of LHRH analogues as adjuvant or neoadjuvant therapy in conjunction with radiation therapy may improve survival outcomes. Few studies have evaluated the use of LHRH analogues after biochemical failure. However, several related studies indicate that initiating hormone therapy earlier rather than later may provide some clinical benefit. When considering early initiation of LHRH therapy, the potential risks of long-term treatment must be considered. Physiologic changes, such as deterioration of body composition and bone quality, may have important effects on the risk of developing cardiovascular disease and osteoporosis. Conclusions: Although some clinical evidence supportsthe use of LHRH analogues as adjuvant or neoadjuvant therapy or following biochemical failure, further study is needed. In the meantime, clinicians should carefully weigh the potential benefits and risks of early hormone therapy when making treatment decisions.

103Pd brachytherapy versus radical prostatectomy in patients with clinically localized prostate cancer: A 12-year experience from a single group practice

Purpose In an effort to shed light on the continuing debate over the best treatment options for patients with localized prostate cancer, we present a retrospective review of patients from a single group community urology practice. Methods and materials Data from 1707 patients were reviewed. These patients, with T1 or T2 adenocarcinoma of the prostate, were treated from 1992 to 2004 with either brachytherapy or radical retropubic prostatectomy (RRPP); 81% were aged over 65 years. Patients were classified into risk groups based on initial prostate-specific antigen (PSA) and Gleason score. Time to PSA-indicated recurrence was used as the measure of disease control and cure. Results Time to PSA-indicated recurrence was used as a measure of efficacy. Brachytherapy with 103Pd exclusively and RRPP were found to provide equivalent control (<0.4 ng/mL for prostatectomy and <3 successive rises in PSA as defined by the American Society for Therapeutic Radiology and Oncology [ASTRO]) in low-risk groups (89% seeds vs. 94% RRPP). In intermediate (89% seeds vs. 58% RRPP) and high-risk (88% seeds vs. 43% RRPP) groups, brachytherapy patients had better control rates. The addition of external radiation, with or without luteinizing hormone-releasing hormone therapy, improved biochemical control rates in intermediate and high-risk brachytherapy groups. Conclusion The results failed to show any superiority of prostatectomy over brachytherapy with 103Pd (TheraSeed; Theragenics Corp., Buford, GA) regarding time until relapse as indicated by PSA level increase (>0.4 ng/mL for prostatectomy and >3 successive rises in PSA as defined by ASTRO). We recently reviewed our techniques and improved equipment from 1995 to present and found major gains with both brachytherapy and surgery. Low risk brachytherapy resulted in 99% freedom from PSA failure while surgery showed results of 97%. Brachytherapy and prostatectomy should be offered without bias to all men with stage T1 and T2 organ-confined prostate cancer.

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.

Bilateral or Unilateral KTP Laser Ovarian Drilling in Polycystic Ovarian Disease

Bilateral or Unilateral KTP Laser Ovarian Drilling in Polycystic Ovarian Disease

Prospective determination of the hormonal response after cessation of luteinizing hormone-releasing hormone agonist treatment in patients with prostate cancer

Objectives. To determine the hormonal (luteinizing hormone [LH] and testosterone) and biochemical (serum prostate-specific antigen [PSA]) response to withdrawal of luteinizing hormone-releasing hormone (LHRH) agonists in patients who received more than 2 years of LHRH therapy for advanced prostate cancer.Methods. Fourteen patients with clinical Stage T3 or higher prostate cancer and no evidence of clinical or biochemical progression, who had received 2 years or more of LHRH therapy, were enrolled at the time of their scheduled 3-month depot injection. Patients underwent history, physical examination, and measurement of serum PSA, LH, and testosterone at baseline, monthly for 3 months, and then every 3 months for 1 year following LHRH withdrawal.Results. The mean age of patients was 70.3 years (range 56 to 84). Patients previously received LHRH agonist for a mean of 38.6 months (range 25 to 82). All patients had castrate levels of testosterone (median 10.0 ng/dL) and suppressed LH levels (median 0.1 mIU/mL) at baseline. Median baseline PSA was 0.15 ng/mL. On multiple groupwise comparison, there was no significant change (compared with baseline) in LH or testosterone until 6 months after withdrawal and no change in PSA throughout the duration of the study (median PSA at 12 months 0.30 ng/mL). Despite significant increases in LH and testosterone when compared with baseline beginning at 6 months, both LH and testosterone remained markedly suppressed, with median testosterone remaining in the castrate range at both 6 and 9 months and significantly below the lower limit of normal at 12 months (median 111.0 ng/dL). Despite no statistically significant change for the entire cohort in serum PSA, a rising PSA was noted in 4 patients between 3 and 9 months, and LHRH therapy was reinitiated. The remaining patients continued to have suppressed LH and testosterone, with 4 patients remaining in the castrate range at 12 months.Conclusions. The recovery of function of the hypothalamic-pituitary-testicular axis after prolonged LHRH administration is variable. Castrate levels of testosterone and suppressed LH may persist even up to 1 year after discontinuing LHRH. These results have significant implications regarding the interpretation of clinical trials incorporating neoadjuvant and adjuvant hormonal therapy. Further studies are needed to expand on these preliminary observations and should also address the feasibility of incorporating LHRH withdrawal into clinical practice.

Unexpected borderline malignant and malignant smooth muscle cell tumors of the uterine corpus in women treated with LH-RH analogues

In this report, two cases of uterine smooth muscle cell tumors, one of uncertain malignant potential and one clearly malignant, are described in women treated for prolonged periods with luteinizing hormone-releasing hormone (LH-RH) analogues. Due to lengthy monitoring of LH-RH therapy, surgical intervention and histologic classification of these tumors was late in the course of disease, resulting in a delay in definite treatment. The risk to these women is discussed. The effects of LH-RH analogue therapy on fibroids is reviewed. Suggestions are put forward for monitoring LH-RH analogue therapy.

Patient compliance in treatment of prostate cancer with luteinizing hormone-releasing hormone (LHRH) agonist

Luteinizing hormone-releasing hormone (LHRH) agonist therapy is commonly used as a form of hormonal ablative therapy in patients with advanced prostate cancer. It is important to administer LHRH agonist every four weeks. Any delay of more than two weeks is associated with the risk of disease flare. A retrospective review of two groups of patients were compared. Twenty-five patients treated at the Veterans Administration Medical Center, Louisville, Kentucky, showed that 44 percent missed one or more injections and 24 percent had a delay of more than two weeks after the scheduled time for another injection. Twenty-three patients were treated by a private practice group in Louisville, Kentucky. There were no problems with compliance. An office nurse kept a separate register for patients receiving LHRH agonist therapy and their appointments. For LHRH therapy to be effective, we believe that the level of compliance one could expect from an individual should be determined before instituting LHRH agonist therapy. If good compliance is not assured, alternative forms of hormone ablative therapy may be preferable for patients with advanced prostate cancer.

Overview of Current Status of Total Androgen Deprivation in Metastasized Prostate Cancer

The incidence and methods available for the diagnosis of metastatic prostate cancer, together with the development and efficacy of various treatments, are discussed. In patients with good prognostic characteristics, maximal androgen deprivation, with blockade of both testicular and adrenal androgens, seems to be the favored approach. Surgical castration, although effective, seems inferior to depot luteinizing hormone-releasing hormone therapy with respect to patients’ acceptance and preference. Nonsteroidal antiandrogens, such as flutamide, have advantages over steroidal compounds both in efficacy and side effects. Recent studies have demonstrated that combination therapy may be superior in terms of progression-free survival and overall survival in patients with metastatic prostate cancer.