Obesity and Sex Steroids during Gonadotropin-Releasing Hormone Agonist Treatment for Prostate Cancer

Smith, Matthew R.

doi:10.1158/1078-0432.ccr-06-2086

Cited by 69 publications

(51 citation statements)

References 32 publications

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“…Despite lower pretreatment serum testosterone levels, obese men have significantly higher testosterone levels during treatment with gonadotropin-releasing hormone (GnRH) agonists than men with normal BMI. 55 The substantially smaller relative decline in testosterone levels after GnRH agonist treatment may contribute to greater cancer-specific mortality in obese men. Additional research is needed to further delineate the relationships between obesity, sex steroid levels, and survival in men receiving ADT.…”

Section: Discussionmentioning

confidence: 99%

Obesity and mortality in men with locally advanced prostate cancer

Efstathiou

Bae

Shipley

et al. 2007

Cancer

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BACKGROUND.Greater body mass index (BMI) is associated with shorter time to prostate‐specific antigen (PSA) failure following radical prostatectomy and radiation therapy (RT). Whether BMI is associated with prostate cancer‐specific mortality (PCSM) was investigated in a large randomized trial of men treated with RT and androgen deprivation therapy (ADT) for locally advanced prostate cancer.METHODS.Between 1987 and 1992, 945 eligible men with locally advanced prostate cancer were enrolled in a phase 3 trial (RTOG 85‐31) and randomized to RT and immediate goserelin or RT alone followed by goserelin at recurrence. Height and weight data were available at baseline for 788 (83%) subjects. Cox regression analyses were performed to evaluate the relations between BMI and all‐cause mortality, PCSM, and nonprostate cancer mortality. Covariates included age, race, treatment arm, history of prostatectomy, nodal involvement, Gleason score, clinical stage, and BMI.RESULTS.The 5‐year PCSM rate for men with BMI <25 kg/m2 was 6.5%, compared with 13.1% and 12.2% in men with BMI ≥25 to <30 and BMI ≥30, respectively (Gray's P = .005). In multivariate analyses, greater BMI was significantly associated with higher PCSM (for BMI ≥25 to <30, hazard ratio [HR] 1.52, 95% confidence interval [CI], 1.02–2.27, P = .04; for BMI ≥30, HR 1.64, 95% CI, 1.01–2.66, P = .04). BMI was not associated with nonprostate cancer or all‐cause mortality.CONCLUSIONS.Greater baseline BMI is independently associated with higher PCSM in men with locally advanced prostate cancer. Further studies are warranted to evaluate the mechanism(s) for increased cancer‐specific mortality and to assess whether weight loss after prostate cancer diagnosis alters disease course. Cancer 2007. © 2007 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Obesity and mortality in men with locally advanced prostate cancer

Efstathiou

Bae

Shipley

et al. 2007

Cancer

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“…Although obese men had a slightly higher level of testosterone, confirming the findings of others, these differences were not clinically significant in this advanced castration-resistant population. 24 A higher level of testosterone in obese men may indicate inadequate testosterone suppression with current dosing regimens of GnRH agonists, and may be more important for androgen-sensitive disease. 24 However, the testosterone threshold for eligibility in clinical trials of men with CRPC should remain less than or equal to 50 ng per 100 ml, given that lower levels were not prognostic of OS.…”

Section: Discussionmentioning

confidence: 99%

The relationship of body mass index and serum testosterone with disease outcomes in men with castration-resistant metastatic prostate cancer

Armstrong

Halabi

Wit

et al. 2008

Prostate Cancer Prostatic Dis

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The purpose of this study was to evaluate the relationship of baseline body mass index (BMI) and serum testosterone level with prostate cancer outcomes in men with castration-resistant metastatic prostate cancer (CRPC). BMI and testosterone levels were evaluated for their ability to predict overall survival (OS) and prostate-specific antigen (PSA) declines in the TAX327 clinical trial, an international phase III randomized trial of one of the two schedules of docetaxel and prednisone compared with mitoxantrone and prednisone. In this study of 1006 men with CRPC, the median serum testosterone level was 14.5 ng per 100 ml (range 0-270), the median BMI was 27 kg m À2 (range 15.7-46.5), and 26% of men were obese or morbidly obese (BMIX30). Obesity was associated with younger age, lower PSA and alkaline phosphatase levels, and higher performance status, primary Gleason sum, testosterone and hemoglobin compared to absence of obesity. In multivariate analysis, neither BMI, presence of obesity, nor baseline testosterone was significantly associated with OS or PSA declines. Higher testosterone levels among obese men suggest incomplete gonadal suppression with current therapies, but these differences may not be clinically relevant in men with CRPC. There was evidence of potential hemodilution of PSA and alkaline phosphatase levels in obese men.

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“…It was shown that despite lower pretreatment serum testosterone levels, obese men (body mass index (BMI) O30 kg/m 2 ) had total and free testosterone levels 1.8 and 2.3 times greater, respectively, than those in normal men after 48 weeks of leuprolide 3-month (22.5 mg) depot treatment (Smith 2007).…”

Section: Introductionmentioning

confidence: 99%

Variations of serum testosterone levels in prostate cancer patients under LH-releasing hormone therapy: an open question

Reis

2012

Endocrine-Related Cancer

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The hypothesis ‘the lower the better when achieving castration levels of testosterone’ is based on the data from second-line hormonal manipulation and its molecular basis, and on better oncological results reported for lower castration levels in prostate cancer (PCa) patients, including those achieved with maximal androgen blockade. In this regard, the equivalence of surgical and different pharmacological castrations has been controversial. The modified amino acid structure that makes LH-releasing hormone (LHRH) analogs more potent than LHRH, and the method of delivering the analogs impacts on bioavailibility and potentially causes differences in androgen levels and in its final oncological efficacy. In addition to this, there is a myriad of circumstances, such as those related to ethnic variations and co-morbidities, which uniquely impact on the pharmacological approach in a highly heterogeneous population of castration-resistant prostate cancer (CRPC) patients. Ineffective testosterone suppression through hormonal escape is currently poorly recognized and may result in increased PCa mortality. Until now, the optimal serum testosterone level in patients under castration, and the impact of its variations in patients under LHRH therapy, remain open questions and have been merged to a broad spectra of patients who are highly heterogeneous. This heterogeneity relates to a number of mechanisms regarding response to treatment, which influences the biology of the relapsing tumor and the sensitivity to subsequent therapies in the individual patient. The rationale to achieve testosterone levels below 20–50 ng/dl warrant further investigation as these levels have recently rescued CRPC patients. In the last few years and months, important advancements in prostate cancer treatment have been achieved. Nevertheless, these advances are measured in a few months of additional survival and under high costs, not available to most of the world population, compared with the benefits of hormonal manipulation that are measured in years, there is a huge potential for accessible and durable effect expansion and optimization of treatment, particularly with the current tendency of a more individual approach.

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Obesity and Sex Steroids during Gonadotropin-Releasing Hormone Agonist Treatment for Prostate Cancer

Cited by 69 publications

References 32 publications

Obesity and mortality in men with locally advanced prostate cancer

Obesity and mortality in men with locally advanced prostate cancer

The relationship of body mass index and serum testosterone with disease outcomes in men with castration-resistant metastatic prostate cancer

Variations of serum testosterone levels in prostate cancer patients under LH-releasing hormone therapy: an open question

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