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Summary. Plasma unconjugated estrone (E~), estradiol-17/3 (E2) and estriol (E3) , and HCS were measured in the same plasma samples collected throughout pregnancy in 19 gestational diabetics (GD) and 21 diabetics (D). When compared to the results obtained in 22 normal subjects, plasma levels of E 1 and E 2 were significantly elevated in D in the second half of gestation. The results were intermediate although closer to the normals, in GD. E 3 values were not different from the normals in both D and GD. HCS values were lower than normal in early pregnancy in both D and GD. In late pregnancy HCS levels were not different from normal in either D or GD, although some individual values were much above the upper limit in some diabetic patients. The hormonal ratios in D and GD parallel those in normals, although E3/E 2 and HCS/E 2 were lower in D. These results are discussed with respect to the different behaviour of E 2 and E3, taking into accotmt the difference in their respective biosynthetic pathways. Besides a possible quantitative modification of the placental function in D, the results could tentatively be explained by a qualitative change in the fetal estrogen precursors to placental aromatization, in favour of the 16-non-hydroxylated compound. However, maternal modifications in precursor production or in estrogen metabolism can be an alternative hypothesis. Finally, the present work does not support the hypothetical estrogen deficiency in diabetic pregnancy. Estrogen treatment appears to have no objective justification.* This work was presented at the 1 lth annual meeting of the E. A.S.D., Munich September 1975 (Abstract 46, Diabetologia 11, 337, 1975.Key words: Estrone, estradiol, estriol, estrogens, diabetes, pregnancy, HCS, gestational diabetes, plasma levels.The hormonal environment in diabetic pregnancy has been the subject of many investigations, which have been extensively reviewed recently [1,2]. These works were aimed at showing the possible occurrence of endocrine dysfunction of the placenta, induced by the maternal diabetic environment, or of the fetus where adaptative mechanisms might have been stimulated by the particular metabolic situation. Yet, estrogen administration has been advocated as a necessary part of the treatment in diabetic pregnancy [3], in view of inferred hormonal insufficiency based on urine analysis [1,4].Controversy has arisen concerning the significance of urinary measurements [5], and conflicting results were reported [6]. Plasma measurements of estrogens also gave inconclusive results depending on the technique used, or the selection of patients [1,4,7], regarding for instance their state of equilibrium or the degree of illness. Low [8], high [9][10], and normal [11][12][13][14][15] values were reported for plasma estrogens. High [16,17] and normal [18,19] values were found for plasma HCS (human chorionic somatomammotropin).In the present study, unconjugated estrogens (estrone, estradiol-17/3 and estriol) and HCS were measured in the same plasma samples of a group of well tr...

Three experiments were carried out in which plasma cortisol concentrations were measured hourly in lambs treated with various anabolic steroids. In the first experiment, female lambs were implanted with trenbolone acetate (TBA) and plasma cortisol was measured for 24-h periods 4 weeks after implantation and 1 week after reimplantation. Plasma cortisol levels were unaltered 4 weeks after treatment, but were found to be significantly lower 1 week after retreatment. On this occasion, peak concentrations of cortisol after ACTH challenge were also reduced by TBA. In the second experiment, female lambs were implanted with a mixture of TBA and oestradiol and plasma cortisol measured 1 and 4 weeks later. Results were similar to the first experiment although the reduction in plasma cortisol was less. In the third experiment, castrated male lambs were implanted with either TBA, TBA plus oestradiol or a long-acting oestradiol implant. In this experiment, only oestradiol affected plasma cortisol levels, causing a large elevation. All three treatments stimulated growth. Measurement of bound and free cortisol concentration in the third experiment indicated that oestradiol treatment tended to increase the proportion of cortisol present in the free form.These results suggest that an inhibition of cortisol secretion may be important in the anabolic response of female sheep to TBA. In the male, however, cortisol concentrations are naturally lower and are not further reduced by TBA treatment.Plasma insulin concentrations were also measured in the castrated males. Neither TBA nor the combined implant altered insulin levels, but oestrogen treatment resulted in a small increase in insulin. The diurnal pattern of plasma insulin closely paralleled that of cortisol.

The effects of the anabolic steroid trenbolone acetate (TBA) on adrenal function and hepatic enzyme activity have been studied in growing female rats. Treatment with TBA resulted in a decrease in the peak of plasma corticosterone concentration which occurred during the afternoon. The enzymes tyrosine aminotransferase (TAT) and phosphoenolpyruvate carboxykinase were measured in the livers of treated and control rats. Activities of both enzymes were maximal at 22.00 h, but that of TAT was reduced in TBA-treated rats. After injection of ACTH, TBA-treated rats showed a smaller increase in plasma corticosterone than did controls. Treatment with TBA did not affect the induction of TAT activity after corticosterone treatment. All TBA-treated rats grew significantly faster than controls and the possible relevance of this reduced adrenal function to the increased growth rate is discussed.

Background and Aims There is little information on the incremental prognostic importance of frailty beyond conventional prognostic variables in heart failure (HF) populations from different country income levels. Methods A total of 3429 adults with HF (age 61 ± 14 years, 33% women) from 27 high-, middle- and low-income countries were prospectively studied. Baseline frailty was evaluated by the Fried index, incorporating handgrip strength, gait speed, physical activity, unintended weight loss, and self-reported exhaustion. Mean left ventricular ejection fraction was 39 ± 14% and 26% had New York Heart Association Class III/IV symptoms. Participants were followed for a median (25th to 75th percentile) of 3.1 (2.0–4.3) years. Cox proportional hazard models for death and HF hospitalization adjusted for country income level; age; sex; education; HF aetiology; left ventricular ejection fraction; diabetes; tobacco and alcohol use; New York Heart Association functional class; HF medication use; blood pressure; and haemoglobin, sodium, and creatinine concentrations were performed. The incremental discriminatory value of frailty over and above the MAGGIC risk score was evaluated by the area under the receiver-operating characteristic curve. Results At baseline, 18% of participants were robust, 61% pre-frail, and 21% frail. During follow-up, 565 (16%) participants died and 471 (14%) were hospitalized for HF. Respective adjusted hazard ratios (95% confidence interval) for death among the pre-frail and frail were 1.59 (1.12–2.26) and 2.92 (1.99–4.27). Respective adjusted hazard ratios (95% confidence interval) for HF hospitalization were 1.32 (0.93–1.87) and 1.97 (1.33–2.91). Findings were consistent among different country income levels and by most subgroups. Adding frailty to the MAGGIC risk score improved the discrimination of future death and HF hospitalization. Conclusions Frailty confers substantial incremental prognostic information to prognostic variables for predicting death and HF hospitalization. The relationship between frailty and these outcomes is consistent across countries at all income levels.