Plasma androgens, IGF-1, body size, and prostate cancer risk: a synthetic review

Abstract

We present a review of the epidemiological evidence for relations of prostate cancer risk to circulating total and bioavailable androgens, to alterations in the metabolism of insulin-like growth factor-1 (IGF-1), and to anthropometric indices of longitudinal growth (body stature) and overweight. In addition, we review the physiological inter-relationships between insulin, growth hormone/IGF-1 axis, and sex steroid metabolism, as well as the associations of bioavailable sex steroid levels with overweight and obesity. A ®rst conclusion of this review is that, taken together, epidemiological studies have provided little support for the hypothesis that prostate cancer risk is increased in men with elevated total or biovailable testosterone (T). Although one prospective study showed an increased risk in men with low plasma sex hormone-binding globulin (SHBG) and with elevated plasma T for given levels of SHBG, this was not con®rmed by results from other cohort studies. A second conclusion is that overweight, which is generally associated with moderate reductions in both total and bioavailable plasma T, appears to be unrelated to any signi®cant increase or decrease in prostate cancer risk. However, signi®cant increases in risk have been observed for men with a taller body stature, or with elevated plasma IGF-1. IGF-1 may directly enhance prostate tumorigenesis by inhibiting apoptosis and by stimulating cell proliferation. In addition, IGF-1 downregulates the synthesis of SHBG, and enhances sex steroid synthesis. Therefore, we do not entirely rule out that due to an elevation of plasma IGF-1 levels, men at increased risk of prostate cancer also have mildly elevated plasma bioavailable T, which epidemiological studies may have failed to demonstrate because of methodological problems. Prostate Cancer and Prostatic Diseases (2000) 3, 157±172.

Leptin and cancer

“…A similar link has been observed for adolescent obesity and prostate cancer deaths, implicating early life events in prostate cancer development (Kaaks et al, 2000). The reasons for the discrepancies observed in the above studies are not clear and could be related to different methodology of data collection and analysis.…”

Reduced risk of prostate cancer among patients with diabetes mellitus

“…18 Furthermore, in both men and women, insulin reduces the hepatic synthesis and plasma levels of SHBG, and in men this is generally accompanied by reductions in circulating testosterone. 19 A metabolic profile very similar to that of obese men is observed in men and women with Type-II, non-insulin dependent diabetes mellitus (NIDDM), which is essentially an extreme state of insulin resistance insufficiently compensated by increased endogenous insulin production. Thus, patients with NIDDM generally show changes in the IGF-I/IGFBP system, as well as in levels of SHBG and circulating androgens similar to those in obese men.…”

Association between serum levels of insulin‐like growth factor‐1, bioavailable testosterone, and pathologic Gleason score

“…The study population comprised patients who underwent RP between 2011 and 2016 at our institution. The serum IGF‐1, IGF binding protein‐3 (IGFBP‐3), testosterone, albumin, and sex hormone‐binding globulin (SHBG) levels, which affect the bioactivity of IGF‐124 and prostate cancer,8 were prospectively measured for all patients. The exclusion criteria were as follows: no extended (≥10 cores) systematic biopsy performed, pathologic T0 (vanishing tumor phenomenon), and incomplete clinical or pathologic data on review.…”

“…Previous epidemiologic studies report that high circulating IGF‐1 is associated with a higher risk of prostate cancer 8, 9. Serial reports from the Health Professionals Follow‐up Study (HPFS), a large prospective cohort study comprising 51 529 male health professionals from the United States, aged 40‐75 years at enrollment in 1986, demonstrate that circulating IGF‐1 level is positively associated with low‐grade, but not with high‐grade, prostate cancer 10, 11, 12.…”