Associations Among Hypogonadism, C-Reactive Protein, Symptom Burden, and Survival in Male Cancer Patients with Cachexia: A Preliminary Report

Fabbro, Egidio Del; Hui, David; Nooruddin, Zohra; Dalal, Shalini; Dev, Rony; Freer, G.; Roberts, Lynn; Palmer, J. Lynn; Bruera, Éduardo

doi:10.1016/j.jpainsymman.2009.09.021

Cited by 46 publications

(37 citation statements)

References 40 publications

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“…In a previous study by our group, we reported a high frequency of hypogonadism (74%) based on TT levels in male cancer patients with cachexia, [8] and slightly lower frequency (64%) based on measurements of FT, [1] compared to the current study. Other groups have recently reported hypogonadism, based on calculated BT <70ng/dl, to be more common in cancer patients with cachexia, 73%, than in cancer patients without weight loss, 53%, and non-cancer control group, 45%.…”

Section: Discussioncontrasting

confidence: 67%

“…BT was also significantly associated with symptom of fatigue and uniquely with poor appetite but not anxiety, sense of well-being, or dyspnea. Previous studies by our group have reported a significant association among low testosterone in male cancer patients with symptoms such as increased fatigue, poor libido, depression, and insomnia [1, 8]. In a recent study, TT was significantly associated with clinical symptom of poor libido while the calculated BT did not show a similar association, and the authors argue to test for both TT and cBT.…”

Section: Discussionmentioning

confidence: 94%

“…[8] Limitations of the study included the absence of serum testosterone measurements in almost one-third of the patient population studied, the lack of testing for free or bio-available testosterone levels, and a small sample size. To address these limitations, the current study examined the association of testosterone - total, free, and bio-available testosterone (TT, FT, BT, respectively) - with symptoms including fatigue and weight loss, laboratory indicators of systemic inflammation, and survival in male patients with advanced cancer.…”

Section: Introductionmentioning

confidence: 99%

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

Dev

Hui

Fabbro

et al. 2014

Cancer

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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.

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Section: Discussioncontrasting

confidence: 67%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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

Dev

Hui

Fabbro

et al. 2014

Cancer

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“…Raised CRP level may be an indicator of acute inflammation, but also may affect appetite more directly, via changes of testosterone levels. Del Fabbro et al found an inverse correlation between testosterone and CRP levels in cachectic men with cancer (Del Fabbro et al 2010). Chronic low-grade inflammation may also suppress appetite by activating serotonin system via increased level of tryptophan (Capuron et al 2011).…”

Section: Comorbiditiesmentioning

confidence: 99%

Mechanisms of the anorexia of aging—a review

Wysokiński

Sobów

Kłoszewska

et al. 2015

AGE

188

148

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Many, even healthy, older people fail to adequately regulate food intake and experience loss of weight. Aging-associated changes in the regulation of appetite and the lack of hunger have been termed as the anorexia of aging. The etiology of the anorexia of aging is multi-factorial and includes a combination of physiological changes associated with aging (decline in smell and taste, reduced central and peripheral drive to eat, delayed gastric emptying), pathological conditions (depression, dementia, somatic diseases, medications and iatrogenic interventions, oral-health status), and social factors (poverty, loneliness). However, exact mechanisms of the anorexia of aging remain to be elucidated. Many neurobiological mechanisms may be secondary to age-related changes in body composition and not associated with anorexia per se. Therefore, further studies on pathophysiological mechanisms of the anorexia of aging should employ accurate measurement of body fat and lean mass. The anorexia of aging is associated with protein-energy malnutrition, sarcopenia, frailty, functional deterioration, morbidity, and mortality. Since this symptom can lead to dramatic consequences, early identification and effective interventions are needed. One of the most important goals in the geriatric care is to optimize nutritional status of the elderly.

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“…Testosterone is the main androgenic hormone involved in a variety of activities in humans [4]. Low levels of testosterone have been associated with a number of chronic inflammatory diseases, including an increase in cardiovascular disease markers [5], mortality [6], diabetes mellitus [7, 8], metabolic syndrome [9], and increased risk for bone fracture [10–15]. High levels of testosterone, due to the use of anabolic androgenic steroids, have also been linked to severe medical consequences including cardiovascular, endocrine, and psychiatric complications [16, 17] suggesting that both sub- and supra-physiologic serum concentrations of testosterone may be pathological.…”

Section: Introductionmentioning

confidence: 99%

Testosterone Regulates Bone Response to Inflammation

Steffens

Herrera²,

Coimbra

et al. 2014

Horm Metab Res

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This study evaluated the alveolar bone response to testosterone and the impact of Resolvin D2 (RvD2) on testosterone-induced osteoblast function. For the in vivo characterization, 60 male adult rats were used. Treatments established sub-physiologic (L), normal (N), or supra-physiologic (H) concentrations of testosterone. Forty rats were subjected to orchiectomy; 20 rats received periodical testosterone injections while 20 rats received testicular sham-operation. Four weeks after the surgeries, 10 rats in each group received a subgingival ligature around the lower first molars to induce experimental periodontal inflammation and bone loss. In parallel, osteoblasts were differentiated from neonatal mice calvariae and treated with various doses of testosterone for 48 h. Cell lysates and conditioned media were used for the determination of alkaline phosphatase, osteocalcin, RANKL, and osteoprotegerin. Micro-computed tomography linear analysis demonstrated that bone loss was significantly increased for both L and H groups compared to animals with normal levels of testosterone. Gingival IL-1β expression was increased in the L group (p < 0.05). Ten nM testosterone significantly decreased osteocalcin, RANKL, and OPG levels in osteoblasts; 100 nM significantly increased the RANKL:OPG ratio. RvD2 partially reversed the impact of 10 nM testosterone on osteocalcin, RANKL, and OPG. These findings suggest that both L and H testosterone levels increase inflammatory bone loss in male rats. While low testosterone predominantly increases the inflammatory response, high testosterone promotes a higher osteoblast-derived RANKL:OPG ratio. The proresolving mediator RvD2 ameliorates testosterone-derived downregulation of osteocalcin, RANKL, and OPG in primary murine osteoblasts suggesting a direct role of inflammation in osteoblast function.

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Associations Among Hypogonadism, C-Reactive Protein, Symptom Burden, and Survival in Male Cancer Patients with Cachexia: A Preliminary Report

Abstract: Our preliminary results suggest that testosterone and CRP may be additive or synergistic as markers for survival in male patients and could be useful in future prognostic models.

Cited by 46 publications

References 40 publications

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

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

Mechanisms of the anorexia of aging—a review

Testosterone Regulates Bone Response to Inflammation

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