Determining dosing intervals for luteinizing hormone releasing hormone agonists based on serum testosterone levels: a prospective study

PURPOSE: Long acting luteinizing hormone releasing hormone agonists are the predominant form of androgen suppression in the treatment of prostate cancer with the goal of maintaining castrate levels of testosterone. Current dosing of luteinizing hormone releasing hormone agonists does not include monitoring the end organ response of serum testosterone. Recent evidence suggests standard dosing regimens fail to achieve castrate levels of testosterone in some patients while in other patients testosterone can remain at castrate levels longer than the manufacturer recommended dosing interval. We prospectively evaluated patients with prostate cancer receiving luteinizing hormone releasing hormone agonist hormonal therapy to determine the length of time that serum testosterone remains at or below castrate levels. MATERIALS AND METHODS: A 3-month dose of 22.5 mg leuprolide was administered to all patients as a first dose followed by a second dose 3 months later. Serum testosterone and prostate specific antigen were measured prospectively before starting hormonal therapy, after the first dose (12 weeks) and again following the second dose (24 weeks) to assess if castrate levels of testosterone (50 ng/dl or less) had been reached. At 24 weeks if patient serum testosterone was 50 ng/dl or less, then 22.5 mg leuprolide were not administered, and serum testosterone and prostate specific antigen were checked monthly. When serum testosterone was greater than 50 ng/dl a subsequent dose of 22.5 mg leuprolide was given. Serum testosterone and prostate specific antigen were then checked 3 months later and monthly thereafter until testosterone was greater than 50 ng/dl. Thus, the time that testosterone remained at castrate levels could be accurately established. RESULTS: From February 2003 to August 2005, 42 patients were treated in this manner with a median followup of 18 months (range 10 to 30). Average patient age was 77 years. Median Gleason grade was 7 (range 6 to 9). Median pretreatment prostate specific antigen was 15.1 ng/ml (range 0.6 to 433) and median posttreatment prostate specific antigen was 0.74 (less than 0.1 to 120). The median dosing interval was 6 months (range 5 to 12). Three patients had an increase in prostate specific antigen while receiving treatment despite castrate levels of testosterone. No patient required more frequent dosing than every 5 months. CONCLUSIONS: Testosterone based luteinizing hormone releasing hormone agonist therapy makes empirical sense. It represents continuous androgen ablation based on the patient physiological end point, namely testosterone. Early data suggest that using serum testosterone to guide luteinizing hormone releasing hormone dosing is safe, efficacious and cost-effective. By following end organ response, patients receive individualized care and more accurate androgen suppression therapy.     

Prostate cancer in men using testosterone supplementation

PURPOSE: Although an association between testosterone supplementation and the development of prostate cancer is unproven, a recent increase in the use of this therapy has reopened the debate about its safety in men at risk for prostate cancer. To increase awareness of this risk, we report on a series of patients in whom clinically significant prostate cancer developed and was presumed to be related to exogenous testosterone use. MATERIALS AND METHODS: The medical records of 6 urology practices were reviewed to identify men undergoing testosterone supplementation for sexual dysfunction or "rejuvenation " who were found to have prostate cancer after initiation of exogenous testosterone supplementation. Cases were analyzed to determine clinical and pathological parameters characterizing the presentation of prostate cancer. RESULTS: A total of 20 men were diagnosed with prostate cancer after initiation of testosterone therapy. Prostate cancer was detected within 2 years of testosterone initiation in 11 men (55%) and from 28 months to 8 years in the remainder. The tumors were of moderate and high grade, being Gleason sum 6, 7 and 8 to 10 in 9 (45%), 6 (30%) and 5 (25%) men, respectively. Median serum prostate specific antigen (PSA) concentration at diagnosis tended to be low at 5.1 ng/ml (range 1.1 to 329.0) and digital rectal examination generally proved more sensitive than PSA assays in detecting the cancer. Patients seen by nonurologist physicians were monitored less often for prostate cancer during testosterone use than those followed by urologists. CONCLUSIONS: Prostate cancer may become clinically apparent within months to a few years after the initiation of testosterone treatment. Digital rectal examination is particularly important in the detection of these cancers. Physicians prescribing testosterone supplementation and patients receiving it should be cognizant of this risk, and serum PSA testing and digital rectal examination should be performed frequently during treatment.     

Failure to maintain the suppressed level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer

A 75-year-old man with metastatic prostate cancer had been treated with goserelin acetate, and prostate specific antigen (PSA) had decreased, but 11/2 years after beginning the treatment of goserelin acetate, PSA was markedly elevated and serum testosterone was at normal level. After castration the serum testosterone was at castrate level and PSA decreased. In the present case, leuprorelin acetate 1-month depot suppressed the luteinizing hormone level in 1 month, even after the patient underwent castration.     

Androgen Replacement Therapy After Prostate Cancer Treatment

Historically, testosterone supplementation has been avoided in men with a history of prostate cancer because of concern about prostate cancer progression or recurrence. However, recently published data suggest that this concern may not be well founded. The recurring presence of prostate-specific antigen in men with hypogonadism being treated with testosterone after prostatectomy is far less than the expected natural recurrence rate of the disease. There are many theories (including the prostate saturation theory) that may help us understand why testosterone may be safely administered in men with hypogonadism after surgical treatment of prostate cancer. Finally, because patients with hypogonadism already may be at a significant disadvantage in recovering their erectile function after prostatectomy, they perhaps should receive special consideration as candidates for androgen replacement therapy.     

Testosterone administration to men with testosterone deficiency syndrome after external beam radiotherapy for localized prostate cancer: preliminary observations

OBJECTIVE

To assess the effects of testosterone supplementation in men with testosterone deficiency syndrome (TDS) after external beam radiotherapy (EBRT) for localized prostate cancer.

PATIENTS AND METHODS

Five men with significant signs of TDS after treatment for localized prostate cancer with EBRT were treated with testosterone once their prostate‐specific antigen (PSA) level had reached the nadir.

RESULTS

The mean (range) level of testosterone before supplementation was 5.2 (1.1–9.2) nmol/L and the duration of follow‐up while on supplementation was 14.5 (6–27) months. At the last visit, the testosterone levels were 17.6 (8.5–32.4) nmol/L. One of the five patients had a transitory increase in PSA level but none had levels of >1.5 ng/mL. All patients reported a marked response in the manifestations of TDS, i.e. four each reported decreased hot flushes, decreased fatigue and improved libido, and two reported improved erectile function.

CONCLUSION

Men with TDS after EBRT for localised prostate cancer are candidates for testosterone therapy. The patients must be aware of the advantages and disadvantages of the treatment. PSA levels must have reached a nadir before starting treatment and the follow‐up must be particularly close. In these few patients there were no adverse effects from testosterone supplementation. There is a need for more information about the safety and efficacy of testosterone therapy in men successfully treated for localized prostate cancer, because there is evidence indicating hypogonadism in these patients, compromising their quality of life and longevity, independent of the cancer.     

The interpretation of serum prostate specific antigen in men receiving 5alpha-reductase inhibitors: a review and clinical recommendations

PURPOSE: We reviewed the effects of 5alpha-reductase inhibitors on prostate specific antigen and clarified the adjustments that should be made to compensate for these effects to ensure that the usefulness of prostate specific antigen for detecting prostate cancer is maintained. MATERIALS AND METHODS: We reviewed articles published in the scientific literature with relevance to the effects of 5alpha-reductase inhibitors on the usefulness of prostate specific antigen for detecting prostate cancer. RESULTS: A total serum prostate specific antigen of 4.0 ng/ml has traditionally been used as the threshold for triggering prostate biopsy. However, clinical trials of finasteride and dutasteride have shown that 5alpha-reductase inhibitors decrease serum prostate specific antigen in patients with and without prostate cancer. To compensate, the doubling rule has been applied in clinical trials and clinical practice. However, doubling serum prostate specific antigen may overestimate actual prostate specific antigen in some patients receiving 5alpha-reductase inhibitors for up to 6 to 9 months, accurately estimate prostate specific antigen from 1 to 3 years and underestimate it thereafter. An increase in prostate specific antigen of 0.3 ng/ml from nadir as a trigger for biopsy maintains 71% sensitivity for prostate cancer in men receiving dutasteride with 60% specificity, similar to the 4.0 ng/ml prostate specific antigen cutoff using placebo. CONCLUSIONS: We propose that a prostate specific antigen increase from nadir of 0.3 ng/ml or greater could represent an alternative to the doubling rule for monitoring prostate specific antigen in patients on 5alpha-reductase inhibitors. The prostate specific antigen increase from nadir appears to be a more accurate cancer indicator than a doubled value in some patients.     

An implant releasing the gonadotropin hormone-releasing hormone agonist histrelin maintains medical castration for up to 30 months in metastatic prostate cancer

PURPOSE: The administration of gonadotropin hormone-releasing hormone agonists is well established for treating metastatic prostate cancer. In an ongoing study we evaluated the effect of a long acting implant that releases the gonadotropin hormone-releasing hormone agonist histrelin ([ImBzl]D-His6,Pro9-Net) in 15 patients with disseminated prostate cancer. MATERIALS AND METHODS: The 2.6 cm. implant releasing 60 microg. histrelin daily is inserted subcutaneously into the upper arm using local anesthesia. Of the patients 8 received 1 and the remainder received 2 implants. Treatment with the antiandrogen flutamide or cyproterone acetate began 2 weeks before implant insertion and continued for up to 12 weeks. Testosterone, luteinizing hormone (LH) and prostate specific antigen were determined monthly, and a metastatic evaluation was performed every 6 months. RESULTS: LH and testosterone increased after flutamide administration and decreased after implant insertion. By day 28 LH and testosterone were completely suppressed. LH and testosterone decreased immediately after cyproterone acetate administration. Prostate specific antigen began to decrease during antiandrogen therapy and decreased further after implant insertion. One patient requested implant removal after 1 year for personal reasons and 1 died of an unrelated cause 18 months after insertion. Escape was demonstrated in 4 cases at 5, 10, 12 and 19 months, although LH and testosterone remained suppressed. Duration of treatment in the remaining 9 patients was between 21 and 30 months. LH and testosterone remained completely suppressed and prostate specific antigen levels were in the normal range. The clinical and biochemical response was identical in those who received 1 or 2 implants. At 12 months 8 patients were challenged at intermittent intervals for up to 24 months with a bolus of 100 microg. gonadotropin hormone-releasing hormone followed by 2 weeks of flutamide. The response was compared with that in untreated controls recently diagnosed with prostate cancer. Unlike controls there was complete LH suppression in the 8 challenged patients. CONCLUSIONS: A histrelin implant suppresses LH and testosterone in prostate cancer for up to 30 months. This finding represents a significant improvement over existing preparations, which must be administered at 1 to 3-month intervals.     

Influence of prostate volume and percent free prostate specific antigen on prostate cancer detection in men with a total prostate specific antigen of 2.6 to 10.0 ng/ml

PURPOSE: Percent free prostate specific antigen and prostate specific antigen density have been independently shown to increase the specificity of prostate cancer screening in men with prostate specific antigen levels between 4.1 and 10.0 ng/ml. Recent data suggest the total prostate specific antigen cutoff for performing a biopsy should be 2.6 ng/ml. We assessed the influence of percent free prostate specific antigen and prostate volume on cancer detection in men with a prostate specific antigen between 2.6 and 10.0 ng/ml. MATERIALS AND METHODS: From 1991 to 2005 all transrectal ultrasound guided prostate biopsies (5,587) for abnormal digital rectal examination and/or increased age specific prostate specific antigen were evaluated. A total of 1,072 patients with a prostate specific antigen between 2.6 and 10.0 ng/ml and any percent free prostate specific antigen were included in study. The cancer detection rate was calculated for each percent free prostate specific antigen/volume stratum. RESULTS: Prostate cancer was detected in 296 patients (27.6%). The mean age and prostate specific antigen of the patients with benign pathology and prostate cancer were similar. Mean percent free prostate specific antigen was 17.5% and 14.1% (p>0.05), and the mean volume was 62.0 and 46.0 cc (p=0.001), respectively. The strongest risk factors for a positive biopsy were percent free prostate specific antigen (odds ratio 0.004, p<0.001), volume (OR 0.977, p<0.001) and digital rectal examination (OR 1.765, p=0.007), but not total prostate specific antigen (p=0.303). When stratified by volume and percent free prostate specific antigen, distinct risk groups were identified. The probability of detecting cancer inversely correlated with prostate volume and percent free prostate specific antigen. CONCLUSIONS: In men with prostate specific antigen levels between 2.6 and 10.0 ng/ml, the probability of detecting cancer was inversely proportional to prostate volume and percent free prostate specific antigen. This table may assist in predicting patient risk for harboring prostate cancer.     

Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systematic review

This paper provides a systematic review of the literature about prostate cancer risk associated with testosterone therapy for hypogonadism. A comprehensive search of MEDLINE, EMBASE and other resources was conducted to identify articles that highlight occurrences of prostate cancer in men receiving testosterone therapy for hypogonadism treatment. Articles that met study inclusion criteria were assessed for causality between testosterone treatment and prostate cancer, increased prostate-specific antigen or abnormal digital rectal examination findings. Of 197 articles relating to testosterone therapy, 44 met inclusion criteria: 11 placebo-controlled, randomized studies; 29 non-placebo-controlled studies of men with no prostate cancer history; and 4 studies of hypogonadal men with history of prostate cancer. Of studies that met inclusion criteria, none demonstrated that testosterone therapy for hypogonadism increased prostate cancer risk or increased Gleason grade of cancer detected in treated vs untreated men. Testosterone therapy did not have a consistent effect on prostate-specific antigen levels.     

Low serum testosterone levels are associated with positive surgical margins in radical retropubic prostatectomy: hypogonadism represents bad prognosis in prostate cancer

PURPOSE: It has been reported that more aggressive prostate cancer (PC) can be associated with low serum testosterone levels. The relationship between serum androgens and PC is still not completely understood. In this study we examined the association of prognostic factors in men who underwent radical retropubic (RRP) prostatectomy with low or normal total testosterone. MATERIALS AND METHODS: We retrospectively evaluated 64 consecutive patients with localized PC treated with RRP between July 2002 and November 2003. PC was diagnosed by transrectal ultrasonography guided biopsy performed for either a suspicious digital rectal examination or serum prostate specific antigen greater than 4.0 ng/ml. Gleason score was determined in prostatic biopsies. Pathological TNM staging (1997), capsular perforation, seminal vesicle involvement and surgical margin status were determined in all surgical specimens. The threshold for serum total testosterone was 270 ng/dl. In all analyses p <0.05 was considered statistically significant. RESULTS: There were no statistically significant differences among prostate specific antigen, Gleason score (biopsy or specimen), pathological stage, capsular perforation and seminal vesicle involvement. However, patients with low total testosterone had increased positive surgical margins (p = 0.026). CONCLUSIONS: Patients with low total testosterone more frequently present with positive surgical margins in RRP specimens. The true association between low testosterone and poor clinical outcome in the long term needs validation in large prospective studies.     

Intermittent androgen suppression for prostate cancer: Canadian Prospective Trial and related observations

The Canadian Prospective Trial of intermittent androgen suppression was a prototype therapeutic initiative started in 1995 for the management of patients in biochemical relapse after radiation for localized prostate cancer. An interim analysis has yielded several observations on the relations between baseline serum prostate specific antigen (PSA), nadir serum PSA, Gleason score, and time off-treatment. In a typical androgen-dependent tumor, the response of serum PSA to androgen withdrawal is biphasic, but with early tumor progression, plateauing of serum PSA is observed. Ligand-independent activation of the androgen receptor, a mechanism subserving the initiation of androgen independence, can be counteracted experimentally with decoy molecules and clinically with nonsteroidal antiandrogens. In some patients, it is possible to lengthen the off-treatment interval by inhibiting the enzyme 5 alpha-reductase, an effect that can be reinforced by lowering serum testosterone with an antigonadotropin. Serial measurements of serum PSA indicate that intermittent androgen suppression engenders a more diverse range of hormone-related responses than previously appreciated. These include: (1) repeated differentiation of tumor with recovery of apoptotic potential; (2) inhibition of tumor growth by rapid restoration of serum testosterone; and (3) restraint of tumor growth by subnormal levels of serum testosterone. These responses are aspects of regulation that should be taken into account when planning long-term treatment of prostate cancer with intermittent androgen suppression.     

经尿道前列腺切除术、经尿道前列腺等离子剜除术治疗BPH患者的术后康复和控尿功能比较及对睾酮、前列腺特异抗原水平的影响

目的 比较分析经尿道前列腺切除术(TURP)、经尿道前列腺等离子剜除术(PKEP)治疗良性前列腺增生(BPH)患者的术后康复、控尿功能及对睾酮(T)、前列腺特异抗原(PSA)水平的影响.方法 将无锡市第九人民医院及复旦大学附属华山医院2017年4月至2019年4月间收治的100例BPH患者随机分为观察组及对照组;对照组...     

Age adjusted prostate specific antigen and prostate specific antigen velocity cut points in prostate cancer screening

PURPOSE: We identified age adjusted prostate specific antigen and prostate specific antigen velocity cut points for prostate cancer biopsy. MATERIALS AND METHODS: A cohort of 33,643 men was retrieved from the Duke Prostate Center database. Of this group 11,861 men with 2 or more prostate specific antigen values within 2 years were analyzed for age adjusted prostate specific antigen and prostate specific antigen velocity performance in cancer risk assessment using a receiver operating characteristic curve. RESULTS: In the 11,861 men prostate cancer prevalence was 273 (8.0%), 659 (14.9%) and 722 (17.9%) in the groups of men 50 to 59 years old, 60 to 69 and 70 years old or older. In prostate cancer groups median prostate specific antigen and prostate specific antigen velocity in men 50 to 59 vs 70 years old or older were 5.6 vs 8.1 ng/ml and 1.37 vs 1.89 ng/ml per year (<0.0001). In men 50 to 59 years old the sensitivity and specificity were 82.1% and 80.7% at prostate specific antigen 2.5 ng/ml, and 84.3% and 72.4% at prostate specific antigen velocity 0.40 ng/ml per year, higher than those in men 70 years old or older at prostate specific antigen 4.0 ng/ml or prostate specific antigen velocity 0.75 ng/ml per year. Decreasing the prostate specific antigen cut point to 2.0 ng/ml and the prostate specific antigen velocity cut point to 0.40 ng/ml per year in men 50 to 59 years old improved the cancer detection rate but decreased the positive predictive value. CONCLUSIONS: Current biopsy guidelines (prostate specific antigen 4.0 ng/ml or greater, or prostate specific antigen velocity 0.75 ng/ml or greater per year) underestimated cancer risk in men 50 to 59 years old. Prostate specific antigen and prostate specific antigen velocity cut points should be age adjusted. In men 50 to 59 years old prostate specific antigen and prostate specific antigen velocity cut points could be decreased to 2.0 ng/ml and 0.40 ng/ml per year, respectively. Factors of age, sensitivity, specificity, positive predictive value and cancer prevalence are critical for obtaining the desired balance between cancer detection and negative biopsy.     

Recovery of serum prostate specific antigen value after interruption of antiandrogen therapy with allylestrenol for benign prostatic hyperplasia

Decrease in serum prostate specific antigen (PSA) concentration is inevitably associated with antiandrogen therapy for benign prostatic hyperplasia (BPH), and might mask the presence of prostate cancer or delay its diagnosis. To determine the appropriate timepoint for determination of correct PSA value, we sequentially measured serum PSA and testosterone levels after discontinuation of antiandrogen therapy for BPH. With informed consent, 12 patients (72.8 +/- 12.2* years old) with BPH were treated with allylestrenol 50 mg/day for 4 months. Serum testosterone and PSA concentrations were determined before and just after treatment, as well as every month after treatment up to 3 months. After treatment with allylestrenol for 4 months, mean serum testosterone and PSA levels were significantly decreased from 408 +/- 136* to 87.9 +/- 76.2* ng/dl, and from 2.81 +/- 0.87* to 2.04 +/- 0.82* ng/ml, respectively. The mean serum PSA level recovered to the pretreatment level within 2 months and mean serum testosterone concentration within one month after discontinuation of administration. In conclusion, during treatment of BPH with antiandrogen allylestrenol, a two-month washout is adequate for determination of correct PSA value (*: M +/- SD).     

Strontium-89 combined with doxorubicin in the treatment of patients with androgen-independent prostate cancer

We investigated the activity of a bone-targeting regimen consisting of strontium-89 and doxorubicin in the treatment of patients with androgen-independent prostate cancer. Three and 22 patients with androgen-independent prostate cancer and bone metastasis received doxorubicin at 15 mg/m² and 20 mg/m², respectively (intravenously by continuous infusion over 24 hours, once per week). All patients received strontium-89 55 μCi/kg, intravenously, every 3 months. Antitumor activity (a prostate specific antigen decrease of ≥75% from baseline) was seen in 32% of evaluable patients. Clinical benefit based on pain relief and performance improvement was achieved in 76% and 40% of patients, respectively. Strontium-89 combined with doxorubicin can be delivered with acceptable toxicities. Strontium-89 combined with doxorubicin is active in the treatment of androgen-independent prostate cancer and may be useful in future studies designed to optimize organ (bone)-specific therapies.     

NAD(P)H‐quinone oxidoreductase 1 silencing aggravates hormone‐induced prostatic hyperplasia in mice

NAD(P)H‐quinone oxidoreductase 1 (NQO1) is a highly inducible flavoprotein known to involve in various cellular defence mechanisms. In this study, we explored whether NQO1 deletion affects hormone‐induced prostatic hyperplasia. Testosterone propionate (3 mg/kg, IP) was injected into wild‐type (WT) and NOQ1 knockout C57BL/6 mice (NQO1^?/?) for 14 consecutive days, and the samples were collected for biological and histochemical studies. The testosterone‐treated NQO1^?/? showed about 140% higher prostate weight than the testosterone‐treated WT, with enhanced connective tissue and hyperplastic glands formations. However, increased dihydrotestosterone level after testosterone treatment was not significantly different between the WT and NQO1^?/?. In contrast, the enhanced nuclear expression of proliferating cell nuclear antigen in NQO1^?/? prostate confirmed aggravated prostatic hyperplasia in NQO1^?/?. Moreover, the expression of heat shock protein (HSP) 90‐α was markedly increased in the NQO1^?/?, and this was supported by increased testosterone‐induced nuclear androgen receptor expression in NQO1‐silenced LNCaP cells. Testosterone‐induced prostate‐specific antigen expression was not reversed in NOQ1‐silenced cells after finasteride treatment. Although the exact role of NQO1 in prostatic hyperplasia remains unclear, the hyperplasia exacerbation due to NQO1 deletion might be independent of type 2 5α‐reductase and might be related to enhanced androgen receptor affinity due to enhanced HSP90‐α expression.     

Testosterone therapy has positive effects on anthropometric measures,metabolic syndrome components (obesity,lipid profile,Diabetes Mellitus control), blood indices,liver enzymes,and prostate health indicators in elderly hypogonadal men

To alleviate late‐onset hypogonadism, testosterone treatment is offered to suitable patients. Although testosterone treatment is commonly given to late‐onset hypogonadism patients, there remains uncertainty about the metabolic effects during follow‐ups. We assessed the associations between testosterone treatment and wide range of characteristics that included hormonal, anthropometric, biochemical features. Patients received intramuscular 1,000 mg testosterone undecanoate for 1 year. Patient anthropometric measurements were undertaken at baseline and at each visit, and blood samples were drawn at each visit, prior to the next testosterone undecanoate. Eighty‐eight patients (51.1 ± 13.0 years) completed the follow‐up period. Testosterone treatment was associated with significant increase in serum testosterone levels and significant stepladder decrease in body mass index, total cholesterol, triglycerides and glycated haemoglobin from baseline values among all patients. There was no significant increase in liver enzymes. There was an increase in haemoglobin and haematocrit, as well as in prostate‐specific antigen and prostate volume, but no prostate biopsy intervention was needed for study patients during 1‐year testosterone treatment follow‐up. Testosterone treatment with long‐acting testosterone undecanoate improved the constituents of metabolic syndrome and improved glycated haemoglobin in a stepladder fashion, with no adverse effects.     

Influence of luteinizing hormone-releasing hormone analogues on serum levels of prostatic acid phosphatase and prostatic specific antigen in patients with metastatic carcinoma of the prostate

Serum concentrations of luteinizing hormone (LH), testosterone, prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) were measured in 16 patients with advanced prostatic cancer before and after treatment with luteinizing hormone-releasing hormone (LHRH) analogue. An initial rise of serum LH and testosterone levels was observed on day 2 of the treatment. Subsequently, serum concentrations of PAP and PSA showed a transient increase on day 5 of the treatment. This indicates that LHRH analogues had better be given in combination with antiandrogens in patients with metastatic carcinoma of the prostate.     

Gonadotropin‐releasing hormone: An update review of the antagonists versus agonists

Gonadotropin‐releasing hormone agonists and antagonists provide androgen‐deprivation therapy for prostate cancer. Unlike agonists, gonadotropin‐releasing hormone antagonists have a direct mode of action to block pituitary gonadotropin‐releasing hormone receptors. There are two licensed gonadotropin‐releasing hormone antagonists, degarelix and abarelix. Of these, degarelix is the more extensively studied and has been documented to be more effective than the well‐established, first‐line agonist, leuprolide, in terms of substantially faster onset of castration, faster suppression of prostate‐specific antigen, no risk for testosterone surge or clinical flare, and improved prostate‐specific antigen progression‐free survival, suggesting a delay in castration resistance. Other than minor injection‐site reactions, degarelix is generally well tolerated, without systemic allergic reactions and with most adverse events consistent with androgen suppression or the underlying condition. In conclusion, degarelix provides a rational, first‐line androgen‐deprivation therapy suitable for the treatment of prostate cancer, with faster onset of castration than with agonists, and no testosterone surge. Furthermore, data suggest that degarelix improves disease control compared with leuprolide, and might delay the onset of castration‐resistant disease. In view of these clinical benefits and the lack of need for concomitant anti‐androgen treatment, gonadotropin‐releasing hormone antagonists might replace gonadotropin‐releasing hormone agonists as first‐line androgen‐deprivation therapy in the future.     

A rational approach to androgen therapy for hypogonadal men with prostate cancer

With earlier detection and improved survival from early stage prostate cancer, it is likely that the numbers of men presenting with hypogonadal symptoms following curative surgery for their cancer will increase. Although testosterone supplementation is effective in improving symptoms of hypogonadism, traditionally such therapy has been contraindicated in patients who have had prostate cancer. This paper reviews the evidence that testosterone therapy can be safely given to selected men with hypogonadism who have had prostate cancer but currently have no evidence of disease by clinical and prostate-specific antigen (PSA) criteria. Such patients should be treated cautiously and followed closely.