Group items tagged

SHBG decreases in response to androgens, and in the presence of hypothyroidism, and insulin resistance.

Plasma SHBG levels tend to increase with increasing age

The apparent metabolic clearance rate of testosterone is decreased in elderly as compared to younger men

Testosterone circulates predominantly bound to the plasma proteins SHBG and albumin, with high and low affinity respectively

Testosterone is secreted in a pulsatile fashion

Current clinical guidelines suggest at least two measurements

In adult men, there is a well-documented diurnal variation (particularly in younger subjects) in testosterone levels, which are highest in the early morning and progressively decline throughout the day to a nadir in the evening

In older men, the diurnal variation is blunted

it is standard practice for samples to be obtained between 0800 and 1100 h.

Testosterone and DHEA decline, whereas LH, FSH, and SHBG rise

DHT remains constant despite the decline of its precursor testosterone

Longitudinal studies show an average annual decline of 1–2% total testosterone levels, with decline in free testosterone more rapid because of increases in SHBG with aging

Massachusetts Male Aging Study (MMAS) data show DHEA, DHEAS, and Ae declining at 2–3% per year

DHT showed no cross-sectional age trend

Androstanediol glucuronide (AAG) declined cross-sectionally with age in the MMAS sample, at 0.6% per year

The EMAS data show that, consistent with the longitudinal findings of MMAS (Figure 1), the core hormonal pattern with increasing age is suggestive of incipient primary testicular dysfunction with maintained total testosterone and progressively blunted free testosterone associated with higher LH

obesity impairs hypothalamic/pituitary function

Androgen deprivation in men with prostate cancer has been associated with increased insulin resistance, worse glycemic control, and a significant increase in risk of incident diabetes

Low serum testosterone is associated with the development of metabolic syndrome 116, 117 and type 2 diabetes. 118 SHBG has been inversely correlated with type 2 diabetes

Improvement in insulin sensitivity with testosterone treatment has been reported in healthy 121 and diabetic 122 adult men

In studies conducted in men with central adiposity, testosterone has been shown to inhibit lipoprotein lipase activity in abdominal adipose tissue leading to decreased triglyceride uptake in central fat depots. 123

The substitution of l-T3 for l-T4 caused a significant weight loss

The substitution of l-T3 for l-T4 caused a significant reduction in lipid parameters

TH action is increased in the liver, and the SHBG increase supports this hypothesis

The changes in serum lipid metabolism parameters are similar to the effects observed with drugs approved for the treatment of dyslipidemia

This differential response appears to be limited to the lipid metabolism and SHBG, whereas no differences in indices of insulin resistance were detected. This is remarkable because hyperthyroid states are associated with an increase in hepatic gluconeogenesis (37), and overt thyrotoxicosis is a known cause of secondary diabetes.

Despite the increase in serum T3, the l-T3 treatment did not cause major changes in cardiovascular or musculoskeletal function, as indicated by the echocardiographic and maximal exercise tolerance tests and DXA studies.

Similarly, no significant differences were observed in blood pressure, heart rate, or endothelial vascular function

In conclusion, the results of this pharmacology, proof-of-concept study indicate that replacement therapy of hypothyroidism with l-T3, compared with l-T4 causes weight loss and favorable changes in the lipid profile without appreciable side effects