Dataset Information

Markers of Iron Flux during Testosterone-Mediated Erythropoiesis in Older Men with Unexplained or Iron-Deficiency Anemia.

ABSTRACT: Testosterone treatment of hypogonadal men improves their hemoglobin, but the mechanism is not understood. To investigate possible mechanisms by which testosterone stimulates erythropoiesis in hypogonadal older men with unexplained or iron-deficiency anemia. The Anemia Trial of The Testosterone Trials, a placebo-controlled study in older, hypogonadal men. Twelve academic medical centers. A total of 95 hypogonadal men (testosterone < 275 ng/mL) ≥65 years with anemia (hemoglobin < 12.7 g/dL). They were classified as having unexplained (n = 58) or iron deficiency anemia (n = 37). Testosterone or placebo gel for 1 year. Markers of iron metabolism during the first 3 months of treatment. Testosterone replacement significantly (P < 0.001) increased hemoglobin in the 58 men who had unexplained anemia (adjusted mean difference 0.58 g/dL; 95% confidence interval, 0.31-0.85). Testosterone replacement tended to increase hemoglobin in the 37 men who had iron deficiency (0.38 g/dL; -0.19, 0.95), but the response was more variable and not statistically significant (P = 0.19). In men with unexplained anemia, testosterone replacement suppressed hepcidin (-8.2 ng/mL; -13.7, -2.7; P = 0.004) and ferritin (-19.6 µg/L; -32.8, -6.3; P = 0.004), but in men with iron deficiency, testosterone replacement did not. The decrease in hepcidin was moderately correlated with the increase in hemoglobin in the men with unexplained anemia (correlation coefficient -0.35, P = 0.01) but not in those with iron deficiency anemia (correlation coefficient -0.07, P = 0.73). Testosterone replacement of older hypogonadal men with unexplained anemia stimulates erythropoiesis associated with increased iron mobilization. This effect appears to be attenuated by iron deficiency.

SUBMITTER: Artz AS

PROVIDER: S-EPMC7500468 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Markers of Iron Flux during Testosterone-Mediated Erythropoiesis in Older Men with Unexplained or Iron-Deficiency Anemia.

Artz Andrew S AS Stephens-Shields Alisa J AJ Bhasin Shalender S Ellenberg Susan S SS Cohen Harvey J HJ Snyder Peter J PJ

The Journal of clinical endocrinology and metabolism 20201101 11

<h4>Context</h4>Testosterone treatment of hypogonadal men improves their hemoglobin, but the mechanism is not understood.<h4>Objective</h4>To investigate possible mechanisms by which testosterone stimulates erythropoiesis in hypogonadal older men with unexplained or iron-deficiency anemia.<h4>Design</h4>The Anemia Trial of The Testosterone Trials, a placebo-controlled study in older, hypogonadal men.<h4>Setting</h4>Twelve academic medical centers.<h4>Participants</h4>A total of 95 hypogonadal me ...[more]

PMID: 32785689

Similar Datasets

Project description:Anemia is common in older adults, but often unexplained. Previously, we conducted a randomized, controlled trial of intravenous (IV) iron sucrose to study its impact on the 6-minute walk test and hemoglobin in older adults with unexplained anemia and ferritin levels of 20-200 ng/mL. In this report, we present for the first time the response of hemoglobin, as well as the dynamic response of biomarkers of erythropoiesis and iron indices, in a pooled analysis of the initially IV iron-treated group of 9 subjects and the subsequently IV iron treated 10 subjects from the delayed treatment group. We hypothesized that there would be a reproducible hemoglobin response from IV iron, and that iron indices and erythropoietic markers would reflect appropriate iron loading and reduced erythropoietic stress. To investigate the biochemical response of anemia to IV iron, we studied the dynamics of soluble transferrin receptor (STfR), hepcidin, erythropoietin (EPO), and iron indices over 12 weeks after treatment. In total, all 19 treated subjects were evaluable: 9 from initial treatment and 10 after cross-over. Hemoglobin rose from 11.0 to 11.7 g/dL, 12 weeks after initiating IV iron treatment of 1000 mg divided weekly over 5 weeks. We found early changes of iron loading after 1-2 IV iron dose: serum iron increased by 184 mcg/dL from a baseline of 66 mcg/dL, ferritin by 184 ng/mL from 68 ng/mL, and hepcidin by 7.49 ng/mL from 19.2 ng/mL, while STfR and serum EPO declined by 0.55 mg/L and 3.5 mU/mL from 19.2 ng/mL and 14 mU/mL, respectively. The erythroid response and evidence of enhanced iron trafficking are consistent with the hypothesis that IV iron overcomes iron deficient or iron-restricted erythropoiesis. These data provide new insight that iron-restricted erythropoiesis is a potential and targetable mechanism for patients diagnosed with unexplained anemia of the elderly and offers support for larger prospective trials of IV iron among anemic older adults of low to normal ferritin.

Project description:ImportanceIn one-third of older men with anemia, no recognized cause can be found.ObjectiveTo determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration.Design, setting, and participantsA double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin ≤12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014.InterventionsTestosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months.Main outcomes and measuresThe percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors.ResultsThe men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95% CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95% CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95% CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline.Conclusions and relevanceAmong older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increases may be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels.Trial registrationclinicaltrials.gov Identifier: NCT00799617.

Dataset Information

Markers of Iron Flux during Testosterone-Mediated Erythropoiesis in Older Men with Unexplained or Iron-Deficiency Anemia.

Publications

Markers of Iron Flux during Testosterone-Mediated Erythropoiesis in Older Men with Unexplained or Iron-Deficiency Anemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets