Association between hypogonadism, symptom burden, and survival in male patients with advanced cancer

Abstract

Background A high frequency of hypogonadism has been reported in male patients with advanced cancer. Objectives To evaluate the association among low testosterone, symptom burden and survival in cancer patients. Methods 119/131 (91%) consecutive male cancer patients had an endocrine evaluation of total/free/bioavailable testosterone (TT, FT, BT, respectively), high-sensitivity C-reactive protein (CRP), vitamin B12, thyroid stimulating hormone, 25-hydroxy vitamin D and cortisol levels when presenting with symptoms of fatigue and/or anorexia-cachexia. Symptoms were evaluated by the Edmonton Symptom Assessment Scale. We examined the correlation with Spearman test and survival with log rank test and Cox-regression analysis. Results The median age was 64; majority were white 85 (71%). Median TT was 209ng/dL (normal ≥200 ng/dL), FT was 4.4 ng/dL (normal ≥9 ng/dL), and BT was 22.0 ng/dL (normal ≥61ng/dL). Low TT, FT, and BT values were all associated with worse fatigue (p≤0.04), poor performance status (p≤0.05), weight loss (p≤0.01), and opioid use (p≤0.005). Low TT and FT were associated with increased anxiety (p≤0.04), decreased feeling of well-being (p≤0.04), and increased dyspnea (p≤0.05); while BT was only associated with anorexia (p=0.05). Decreased TT, FT, and BT values were all significantly associated with elevated CRP, low albumin and hemoglobin. In multivariate analysis, decreased survival was associated with low TT (HR 1.66; p=0.034), declining ECOG performance status (HR 1.55; p=0.004), high CRP (HR 3.28; p<0.001), and decreased albumin (HR 2.52; p<0.001). Conclusion In male cancer patients, low testosterone was associated with systemic inflammation, weight loss, increased symptom burden, and decreased survival.

Clinical significance of androgen secretion disorders in men with a malignancy

“…The relationship between low testosterone concentrations and negative survival prognosis has been confirmed by other authors [86]. Men with advanced cancers and androgen deficiency present with fatigue, anxiety, impaired well-being, a worse performance status according to Eastern Cooperative Oncology Group (ECOG), appetite loss and increased inflammatory parameters [86, 88]. In summary, androgen deficiency plays an important role in complex disorders accounting for cancer cachexia syndrome.…”

“…Low concentrations of free testosterone are associated with weight loss and shorter overall survival in men with pancreatic cancer [90]. The relationship between low testosterone concentrations and negative survival prognosis has been confirmed by other authors [86]. Men with advanced cancers and androgen deficiency present with fatigue, anxiety, impaired well-being, a worse performance status according to Eastern Cooperative Oncology Group (ECOG), appetite loss and increased inflammatory parameters [86, 88].…”

The Implications of Low Testosterone on Mortality in Men

“…Most of these studies (85%) found that low levels of testosterone or dihydrotestosterone (DHT), an active metabolite of testosterone, were associated with increased overall mortality [13, 14, 23, 27–38] but some did not. [38–42]. Two studies found that high levels of testosterone were associated with increased mortality in men with cancer.…”

“…Two studies found that high levels of testosterone were associated with increased mortality in men with cancer. [38, 42] (Table 1). …”

Is regular systemic opioid analgesia associated with shorter survival in adult patients with cancer? A systematic literature review

“…cancer progression, recurrence and survival) [28]. In patients with advanced cancer, the systemic inflammatory response and cachexia decrease survival; opioids, via immune and endocrine effects, might influence cancer progression/recurrence and survival, although the overall effect of morphine on these outcomes in clinical practice is poorly understood [28][29][30][31].…”