Serum Estradiol Associates With Blood Hemoglobin in Elderly Men: The MrOS Sweden Study
Catharina LewerinHerman Nilsson‐EhleStefan JacobssonHelena JohanssonValter SundhMagnus K. KarlssonMattias LorentzonElizabeth Barrett‐ConnorLiesbeth VandenputClaes OhlssonDan Mellström
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Blood hemoglobin (Hb) declines with age in healthy elderly men, in whom decreasing T has been regarded as part of normal aging. However, the association between Hb and serum estradiol is incompletely known.To determine whether estradiol is associated with anemia/Hb and established determinants of Hb in elderly men without prostate cancer.The MrOS (Osteoporotic Fractures in Men) is a population-based study (n = 918; median age, 75.3 y; range, 70-81 y).We evaluated total estradiol in relation to Hb and adjusted for potential confounders (ie, age, body mass index [BMI], erythropoietin [EPO], total T, cystatin C, and iron and B-vitamin status).Estradiol correlated negatively with age (r = -0.14; P < .001). Hb correlated (age adjusted) positively with estradiol (r = 0.21; P < .001) and T (r = 0.10; P < .01). Independent predictors for Hb in multivariate analyses were estradiol, EPO, BMI, transferrin saturation, cystatin C, and free T4, but not T. After exclusion of subjects with Hb <130 g/L and/or T < 8 nmol/L (n = 99), the correlation between Hb and T was no longer significant, whereas the associations between Hb and estradiol remained. After adjusting for age, BMI, and EPO, men with lower estradiol levels were more likely to have Hb in the lowest quartile of values (odds ratio per SD decrease in estradiol = 1.61 [95% confidence interval, 1.34-1.93]). Anemic subjects (Hb < 130 g/L) had lower mean estradiol than nonanemic subjects (67.4 vs 79.4 pmol/L; P < .001).Estradiol correlated positively and independently with Hb. Decreased estradiol might partly explain the age-related Hb decline observed in healthy elderly men.Keywords:
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Low doses of estradiol benzoate (2.5-10.0 μg/day X 5) inhibited the production of erythropoietin (Ep) in female rats exposed to various intensities of hypoxia. This was not attributable to the presence of either residual estradiol, or an inhibitor of Ep in plasma samples, since these plasmas had no inhibitory effect on Ep simultaneously injected into assay mice. Although normal females produced less Ep in response to hypoxia than normal males, ovariectomized rats showed a response equal to males. Estradiol treatment of ovariectomized animals lowered their Ep response to hypoxia down to the level of intact females. Only the largest dose employed (10.0 μ/day) had some inhibitory effect on Ep production in hypoxic males. (Endocrinology92: 358, 1973)
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Correction of anaemia with recombinant human erythropoietin (rHu-EPO) improves the responsiveness of thyroidal and gonadal axes to exogenous TRH and GnRH in chronic haemodialysis patients, but the mechanisms remain to be fully elucidated. In order to assess the influences of endogenous erythropoietin on the hypothalamo-hypophyseal thyroidal and gonadal axes, we studied the response of polycythaemic and anaemic patients, in comparison to normal controls, after the administration of exogenous TRH and GnRH.Exogenous hypothalamic factors, 500 micrograms TRH and 100 micrograms GnRH, were administered as a bolus and blood samples were obtained over a 3-hour period at 30, 60, 90, 120 and 180 minutes.Five male polycythaemic patients (low EPO), three male anaemic patients (high EPO) and six normal age and sex matched controls were studied.Blood samples were centrifuged immediately and the serum was stored at -20 degrees C until assayed for total T4, free T4, free T3, TSH, prolactin, growth hormone (TRH test), and FSH, LH, testosterone (GnRH test). Haematological parameters and biochemical profiles were also measured.After TRH administration, both patient groups showed a normal TSH response; however, their free T4 and free T3 secretion was blunted compared to controls. Normal basal PRL levels increased in an exaggerated fashion, whereas, when compared to chronic renal failure patients on chronic haemodialysis, we did not see a paradoxical GH response or a basal GH increase in these 5 patients. GnRH administration in the study groups elicited a normalization in the LH response without an increase in testosterone levels; however, an exaggerated FSH response was found in the polycythaemic patients (low EPO).Thus by investigating the role of low endogenous EPO levels in non-anaemic and anaemic patients with high EPO levels, our study suggests that the underlying chronic disease state may be the major contributing factor in the regulation of the hypothalamo-hypophyseal thyroid and gonadal axes, rather than the EPO levels.
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Multiple myeloma is very frequently associated with anemia which has the character of hypoproliferative anemia of chronic diseases. In this type of anemia there is often insufficient production of endogenous erythropoietin. According to literature pharmacological doses of erythropoietin result in the increase of blood hemoglobin concentration. Erythropoietin (Eprex Cilag) was given to 11 patients whose hemoglobin concentration in blood was lower than 100 g/l. 10 patients could be evaluated at the end of the study. Within the first month all patients were given erythropoietin in the dose of 150 U/kg 3 times a week. The dose was doubled, when the blood hemoglobin concentration did not increase by more than 10 g/l within the first month. In patients with hemoglobin level above 120 g/l we were trying to find the individual maintenance dose. In patients who had not reached a blood hemoglobin concentration increase of at least 20 g/l, as compared with the initial level, further erythropoietin administration was stopped. The concentration of hemoglobin increased of 20 g/l in 8 (80%) out of 10 patients evaluated. All 5 patients who responded within the first month, had had pretreatment concentration of endogenous erythropoietin below 60 U/l. Three other patients had not been responding before their dose of erythropoietin was increased in the 2nd and 3rd months of therapy. The therapy response appeared only in the 2nd and the 3rd months of treatment. These 3 patients had higher pretreatment concentrations of endogenous erythropoietin, from 100 to 350 U/l. During the treatment no adverse effects of erythropoietin were observed. Erythropoietin is a useful drug for anemic patients with the diagnosis of multiple myeloma. According to the results mentioned above and also according to the data from literature it is evident that in patients with the endogenous blood erythropoietin value below 100 U/l it is possible to expect a sudden rise in hemoglobin concentration already within the first month. Patients with a higher concentration of endogenous erythropoietin (100 to 500 U/l) respond to the therapy less frequently and for the increase in hemoglobin it is necessary to give higher doses of erythropoietin. Patients with the initial value of erythropoietin above 500 U/l are not likely to respond.
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Growth hormone (GH) and insulin-like growth factor-I (IGF-I) play important roles in erythropoiesis and erythro-poietin (EPO) secretion. We examined the effects of GH and IGF-I on EPO production in adult rat kidney and liver in vivo and in vitro . Male Wistar rats aged 8–10 weeks were used. Recombinant human GH (hGH) was continuously infused (20 μg/kg per h) subcutaneously for 48 h using a micro-osmotic infusion pump. Octreotide (10 μg/kg) was subcutaneously injected every 12 h beginning 12 h before the hGH treatment. GH increased plasma EPO levels earlier than it increased plasma IGF-I levels. At 24 h, the IGF-I content in the liver and kidney was increased from 172.8±14.6 to 232.6±17.8 ng/g tissue (means±S.E.) and from 53.8±3.1 to 112.8±7.2 ng/g tissue, respectively. The EPO content in the liver was increased from 7.5±1.2 to 15.1±1.4 mIU/g tissue at 48 h, whereas the EPO content in the kidney was decreased at 12, 24, and 48 h after the start of hGH treatment. When the kidneys were organ-cultured, hGH considerably decreased EPO levels in the culture medium in a dose-related manner. The addition of anti-hGH IgG blunted the GH-induced inhibition of EPO secretion from the kidneys. IGF-I also decreased EPO levels in the medium in a dose-related manner. The addition of anti-IGF-I IgG blunted the IGF-I-induced inhibition of EPO secretion from the kidneys, whereas the GH-induced inhibition of EPO secretion was not affected. These findings suggest that both hGH and IGF-I have direct inhibitory effects on EPO secretion from adult rat kidneys.
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We have studied the effect of dietary vitamin D restriction on serum levels of vitamin D metabolites in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Both WKY and SHR were fed a vitamin D-deficient or a vitamin D-supplemented diet beginning at 4 wk of age. In vitamin D-supplemented animals, the serum 1,25-dihydroxycholecalciferol [1,25(OH)2D3] concentration of WKY (55.4+/- 6.6 pg/ml, n = 5) was similar to the level of SHR (46.3+/- 5.9 pg/ml, n = 5). Plasma calcium concentration was not different between WKY and SHR. In animals fed a vitamin D-deficient diet, the serum concentration of 1,25-(OH)2D3 of SHR (23.0+/- 1.3 pg/ml, n = 5) was significantly lower than that of WKY (67.6+/- 4.6 pg/ml, n = 5, P less than 0.01). Plasma 25-hydroxycholecalciferol level was markedly decreased in both WKY (3.6+/- 0.5 ng/ml, n = 7) and SHR (2.8+/- 0.4 ng/ml). The SHR, but not the WKY, developed hypocalcemia (WKY, 9.68 mg/dl; SHR, 6.70 mg/dl). Despite hypocalcemia, fasting urinary Ca2+ excretion of SHR exceeded that of WKY. We conclude that the lower 1,25(OH)2D3 level in SHR fed a vitamin D-deficient diet may be due to a defect in the synthesis of 1,25(OH)2D3. The low level of 1,25(OH)2D3 is associated with renal wasting of calcium and hypocalcemia in SHR.
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Goal: to examine the level of erythropoietin among patients with diabetes mellitus type 1 (DM 1) and different types of anemia and stages of diabetic nephropathy. Materials and methods: erythropoietin level analysis were conducted among 121 patients with DM 1 with and without anemia. Results: patients suffering from DM type 1 with anemia for less than 5 years have higher erythropoietin rates, than those who have DM for 5-15 years and longer time. Patients who suffer from DM for more than 15 years have the same erythropoietin rates regardless of the fact if they also have anemia or not. DM patients with anemia experience the decrease of erythropoietin level as far as Chronic Kidney Disease (CKD) is progressing. This decrease becomes statistically significant among patients with CKD of the 3, 4, and 5 stages (in comparison with patients without diabetic nephropathy (p=0,00)). Patients with Anemia Chronic Disease (ACD) and CKD have the same erythropoietin rates as patients without anemia (p=0,93 and p=0,40). Conclusion: The longer patients suffer from DM 1 and the CKD progress, the more the level of erythropoietin is going down. At duration DM 1 more than 15 years level of erythropoietin at patients DM with anemia corresponds to level of erythropoietin at patients without anemia. Patients with ACD don't have correlation of level of hemoglobin with erythropoietin. Where there is ACD, no hemoglobin-related increase in erythropoietin level is observed (which can be the reason of its appearance and advance). Patients with iron deficiency anemia, have elevating the level of erythropoietin despite an appreciable lesion of function of kidneys.
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Objective To detect the level of serum erythropoietin in patients with hematologic malignancies(HM) and the response of patients to erythropoietin.Methods Serum erythropoietin levels were detected by ELISA in patients with HM,with non-cancer-related anemia and normal individuals.Hemoglobin(Hb) and reticulocyte were also detected in each group.Results The erythropoietin,hemoglobin and reticulocyte was(2.72±1.50) μg/L,(87.20±11.20) μg/L and(2.60±0.98)% in patients with HM;(1.59±0.69) μg/L,(136.1±11.3) g/L and(1.17±0.35)% in normal controls;(2.78±1.53) μg/L,(90.5±9.60) g/L and(5.46±2.12)% in patients with non-cancer-related anemia,respectively.There was significant difference in the level of erythropoietin,hemoglobin and reticulocyte of patients with HM compared with normal control(P0.01).There was significant difference in the level of erythropoietin and hemoglobin between patients with HM and with non-cancer-related anemia(P0.01).Conclusions The level of erythropoietin of patients with HM was responsively increased but the reactivity of body to the erythropoietin was weakened.The anemia of patients with HM may be related to this result.
Reticulocyte
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The erythropoietic activity in the sera of 18 patients with sideropenic anemia was investigated. The ex-hypoxic mouse bioassay was used and the 48 hour incorporation of radioiron into the peripheral blood was measured. The level of erythropoietin found was compared to the hemoglobin concentration and the PCV values in those patients. The statistically significant correlation was found between erythropoietin in the patients sera and the degree of anemia. Higher erythropoietin values were found in men as compared to women with the same severity of anemia. It was concluded that the results obtained in this study can be used as control values when erythropoietic activity in the sera of patients with different hematological disorders is measured.
Iron Isotopes
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To investigate the efficacy and the safety of recombinant human erythropoietin(rHuEPO) for the treatment of chemo-radiotherapy induced anemia.Forty-five patients with chemo-radiotherapy induced anemia were randomized into EPO group and control group.The EPO group was received rHuEPO 10000U,once every other day,subcutaneous for 6 weeks,and iron sulfate 300mg,tid,orally after one week of EPO administered.No EPO was received in the control group.The treatment except EPO was the same in the 2 groups.Hemoglobin,blood transfusion,quantity of life and side effect were compared between the 2 groups.The average hemoglobin level increased 20.1g/L in EPO group,decreased 9.8 g/L in control group(P0.001).The average value of KPS increased in EPO group and decreased in control group.Application of EPO had less side effects which was tolerable.[Conclusions]rHuEPO is effective and safe for the treatment of chemo-radiotherapy induced anemia.
Subcutaneous injection
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