Prediagnostic circulating sex hormones are not associated with mortality for men with prostate cancer

Boris Gershman; Irene M. Shui; Meir Stampfer; Elizabeth A. Platz; Peter H. Gann; Howard L. Sesso; Natalie Dupre; Edward Giovannucci; Lorelei A. Mucci

doi:10.1016/j.eururo.2013.01.003

Prediagnostic circulating sex hormones are not associated with mortality for men with prostate cancer

Boris Gershman, Irene M. Shui, Meir Stampfer, Elizabeth A. Platz, Peter H. Gann, Howard L. Sesso, Natalie Dupre, Edward Giovannucci, Lorelei A. Mucci

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Background: Sex hormones play an important role in the growth and development of the prostate, and low androgen levels have been suggested to carry an adverse prognosis for men with prostate cancer (PCa). Objective: To examine the association between prediagnostic circulating sex hormones and lethal PCa in two prospective cohort studies, the Physicians' Health Study (PHS) and the Health Professionals Follow-up Study (HPFS). Design, setting, and participants: We included 963 PCa cases (700 HPFS; 263 PHS) that provided prediagnostic blood samples, in 1982 for PHS and in 1993-1995 for HPFS, in which circulating sex hormone levels were assayed. Outcome measures and statistical analysis: The primary end point was lethal PCa (defined as cancer-specific mortality or development of metastases), and we also assessed total mortality through March 2011. We used Cox proportional hazards models to evaluate the association of prediagnostic sex hormone levels with time from diagnosis to development of lethal PCa or total mortality. Results and limitations: PCa cases were followed for a mean of 12.0 ± 4.9 yr after diagnosis. We confirmed 148 cases of lethal PCa and 421 deaths overall. Using Cox proportional hazard models, we found no significant association between quartile of total testosterone, sex hormone binding globulin (SHBG), SHBG-adjusted testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, or estradiol and lethal PCa or total mortality. In subset analyses stratified by Gleason score, TNM stage, age, and interval between blood draw and diagnosis, there was also no consistent association between lethal PCa and sex hormone quartile. Conclusions: We found no overall association between prediagnostic circulating sex hormones and lethal PCa or total mortality. Our null results suggest that reverse causation may be responsible in prior studies that noted adverse outcomes for men with low circulating androgens.

Original language	English (US)
Pages (from-to)	683-689
Number of pages	7
Journal	European Urology
Volume	65
Issue number	4
DOIs	https://doi.org/10.1016/j.eururo.2013.01.003
State	Published - Apr 2014

Keywords

Androgens
Mortality
Prostate cancer
Sex hormones
Testosterone

ASJC Scopus subject areas

Urology

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10.1016/j.eururo.2013.01.003

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@article{4af7043eb46640dd967d73b7fd9fea54,

title = "Prediagnostic circulating sex hormones are not associated with mortality for men with prostate cancer",

abstract = "Background: Sex hormones play an important role in the growth and development of the prostate, and low androgen levels have been suggested to carry an adverse prognosis for men with prostate cancer (PCa). Objective: To examine the association between prediagnostic circulating sex hormones and lethal PCa in two prospective cohort studies, the Physicians' Health Study (PHS) and the Health Professionals Follow-up Study (HPFS). Design, setting, and participants: We included 963 PCa cases (700 HPFS; 263 PHS) that provided prediagnostic blood samples, in 1982 for PHS and in 1993-1995 for HPFS, in which circulating sex hormone levels were assayed. Outcome measures and statistical analysis: The primary end point was lethal PCa (defined as cancer-specific mortality or development of metastases), and we also assessed total mortality through March 2011. We used Cox proportional hazards models to evaluate the association of prediagnostic sex hormone levels with time from diagnosis to development of lethal PCa or total mortality. Results and limitations: PCa cases were followed for a mean of 12.0 ± 4.9 yr after diagnosis. We confirmed 148 cases of lethal PCa and 421 deaths overall. Using Cox proportional hazard models, we found no significant association between quartile of total testosterone, sex hormone binding globulin (SHBG), SHBG-adjusted testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, or estradiol and lethal PCa or total mortality. In subset analyses stratified by Gleason score, TNM stage, age, and interval between blood draw and diagnosis, there was also no consistent association between lethal PCa and sex hormone quartile. Conclusions: We found no overall association between prediagnostic circulating sex hormones and lethal PCa or total mortality. Our null results suggest that reverse causation may be responsible in prior studies that noted adverse outcomes for men with low circulating androgens.",

keywords = "Androgens, Mortality, Prostate cancer, Sex hormones, Testosterone",

author = "Boris Gershman and Shui, {Irene M.} and Meir Stampfer and Platz, {Elizabeth A.} and Gann, {Peter H.} and Sesso, {Howard L.} and Natalie Dupre and Edward Giovannucci and Mucci, {Lorelei A.}",

note = "Funding Information: Funding/Support and role of the sponsor: This study was funded in part by grants from the National Institutes of Health/National Cancer Institute (RO1 CA136578 PI: Mucci; P01 CA055075 PI: Willett; R01 CA133891 PI: Giovannucci; R01 CA141298 PI: Stampfer; DF/HCC SPORE in Prostate Cancer NIH/NCI P50 CA90381 PI: Kantoff). Lorelei A. Mucci was a Milken Young Investigator of the Prostate Cancer Foundation. Irene M. Shui is supported by the National Cancer Institute NRSA T32 CA09001 (PI: Stampfer) and a US Army Prostate Cancer Postdoctoral Fellowship. ",

year = "2014",

month = apr,

doi = "10.1016/j.eururo.2013.01.003",

language = "English (US)",

volume = "65",

pages = "683--689",

journal = "European Urology",

issn = "0302-2838",

publisher = "Elsevier",

number = "4",

}

TY - JOUR

T1 - Prediagnostic circulating sex hormones are not associated with mortality for men with prostate cancer

AU - Gershman, Boris

AU - Shui, Irene M.

AU - Stampfer, Meir

AU - Platz, Elizabeth A.

AU - Gann, Peter H.

AU - Sesso, Howard L.

AU - Dupre, Natalie

AU - Giovannucci, Edward

AU - Mucci, Lorelei A.

N1 - Funding Information: Funding/Support and role of the sponsor: This study was funded in part by grants from the National Institutes of Health/National Cancer Institute (RO1 CA136578 PI: Mucci; P01 CA055075 PI: Willett; R01 CA133891 PI: Giovannucci; R01 CA141298 PI: Stampfer; DF/HCC SPORE in Prostate Cancer NIH/NCI P50 CA90381 PI: Kantoff). Lorelei A. Mucci was a Milken Young Investigator of the Prostate Cancer Foundation. Irene M. Shui is supported by the National Cancer Institute NRSA T32 CA09001 (PI: Stampfer) and a US Army Prostate Cancer Postdoctoral Fellowship.

PY - 2014/4

Y1 - 2014/4

N2 - Background: Sex hormones play an important role in the growth and development of the prostate, and low androgen levels have been suggested to carry an adverse prognosis for men with prostate cancer (PCa). Objective: To examine the association between prediagnostic circulating sex hormones and lethal PCa in two prospective cohort studies, the Physicians' Health Study (PHS) and the Health Professionals Follow-up Study (HPFS). Design, setting, and participants: We included 963 PCa cases (700 HPFS; 263 PHS) that provided prediagnostic blood samples, in 1982 for PHS and in 1993-1995 for HPFS, in which circulating sex hormone levels were assayed. Outcome measures and statistical analysis: The primary end point was lethal PCa (defined as cancer-specific mortality or development of metastases), and we also assessed total mortality through March 2011. We used Cox proportional hazards models to evaluate the association of prediagnostic sex hormone levels with time from diagnosis to development of lethal PCa or total mortality. Results and limitations: PCa cases were followed for a mean of 12.0 ± 4.9 yr after diagnosis. We confirmed 148 cases of lethal PCa and 421 deaths overall. Using Cox proportional hazard models, we found no significant association between quartile of total testosterone, sex hormone binding globulin (SHBG), SHBG-adjusted testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, or estradiol and lethal PCa or total mortality. In subset analyses stratified by Gleason score, TNM stage, age, and interval between blood draw and diagnosis, there was also no consistent association between lethal PCa and sex hormone quartile. Conclusions: We found no overall association between prediagnostic circulating sex hormones and lethal PCa or total mortality. Our null results suggest that reverse causation may be responsible in prior studies that noted adverse outcomes for men with low circulating androgens.

AB - Background: Sex hormones play an important role in the growth and development of the prostate, and low androgen levels have been suggested to carry an adverse prognosis for men with prostate cancer (PCa). Objective: To examine the association between prediagnostic circulating sex hormones and lethal PCa in two prospective cohort studies, the Physicians' Health Study (PHS) and the Health Professionals Follow-up Study (HPFS). Design, setting, and participants: We included 963 PCa cases (700 HPFS; 263 PHS) that provided prediagnostic blood samples, in 1982 for PHS and in 1993-1995 for HPFS, in which circulating sex hormone levels were assayed. Outcome measures and statistical analysis: The primary end point was lethal PCa (defined as cancer-specific mortality or development of metastases), and we also assessed total mortality through March 2011. We used Cox proportional hazards models to evaluate the association of prediagnostic sex hormone levels with time from diagnosis to development of lethal PCa or total mortality. Results and limitations: PCa cases were followed for a mean of 12.0 ± 4.9 yr after diagnosis. We confirmed 148 cases of lethal PCa and 421 deaths overall. Using Cox proportional hazard models, we found no significant association between quartile of total testosterone, sex hormone binding globulin (SHBG), SHBG-adjusted testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, or estradiol and lethal PCa or total mortality. In subset analyses stratified by Gleason score, TNM stage, age, and interval between blood draw and diagnosis, there was also no consistent association between lethal PCa and sex hormone quartile. Conclusions: We found no overall association between prediagnostic circulating sex hormones and lethal PCa or total mortality. Our null results suggest that reverse causation may be responsible in prior studies that noted adverse outcomes for men with low circulating androgens.

KW - Androgens

KW - Mortality

KW - Prostate cancer

KW - Sex hormones

KW - Testosterone

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SN - 0302-2838

VL - 65

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EP - 689

JO - European Urology

JF - European Urology

IS - 4

ER -

Prediagnostic circulating sex hormones are not associated with mortality for men with prostate cancer

Abstract

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