Hypogonadism in male patients with cancer.

Background: Patients with cancer often develop anorexia, fatigue, and decreased muscle mass. These signs and symptoms are nonspecific, and they frequently occur in other conditions, including hypogonadism.

Methods: The objectives of this study were 1) to measure testosterone levels in patients with cancer and 2) to examine the correlations between testosterone, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), ghrelin levels, and appetite in patients with cancer patients and in a noncancer control group. This was designed as a cross-sectional study in the setting of a university-affiliated Veterans Affairs Medical Center. The study population included 31 male patients with cancer and 25 gender-matched noncancer controls of similar age. The variables total testosterone (TT), calculated free testosterone (cFT), calculated bioavailable testosterone (cBT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), TNF-alpha, IL-6, IGF-1, and active ghrelin were measured in fasting morning plasma samples. Appetite was measured according to a visual analog scale. The main outcome measures were cFT and cBT.

Results: Cancer patients had mean TT levels similar to levels in the noncancer control group but significantly lower levels of cFT, cBT, IGF-1, and appetite. SHBG, LH, TNF-alpha, IL-6, and ghrelin levels were increased in patients with cancer compared with the control group. cFT and cBT levels were correlated inversely with IL-6 and ghrelin levels and were correlated directly with IGF-1 levels and appetite.

Conclusions: Patients with cancer had lower levels of biologically active testosterone. TT was not adequate for the evaluation of hypogonadism, because SHBG levels were increased. A reliable measurement of FT and/or BT should be used. LH was elevated in the patients with cancer, indicating that low FT levels were caused by primary testicular dysfunction. The authors postulated that high IL-6 or ghrelin levels inhibit testosterone synthesis, although a secondary effect at the hypothalamic-pituitary levels cannot be excluded.