Depressed plasma testosterone and fractional binding of testosterone in obese males.

Plasma testosterone (T), fractional binding of T to T-binding globulin (TeBG), LH, and FSH were evaluated in 22 obese men. Only 1 of 12 men weighing from 176-200% of ideal body weight (group I) had a low T concentration, while 9 of 10 men greater than 200% of ideal weight (group II) had plasma T concentrations 2 SD below the normal mean. The fractional binding of T to TeBG was equally and significantly decreased in both groups. As a result, the mean and individually calculated free T concentrations (free T index) were normal in group I. In contrast, the mean free T index in group II was significantly less than normal males and group I. Individually, 1 of 7 group II men had a free T index 2 SD below the normal mean. LH and FSH were normal in both groups. These studies indicate that in most obese males a low or low normal T is offset by decreased binding to TeBG, resulting in a normal free T index. However, some morbidly obese males are unable to alter their hypothalamic-hypophyseal-gonadal axis to maintain a normal free T index.     

Empirical estimation of free testosterone from testosterone and sex hormone-binding globulin immunoassays

BACKGROUND: The growing interest in measuring blood free testosterone (FT) is constrained by the unsuitability of the laborious reference methods for wider adoption in routine diagnostic laboratories. Various alternative derived testosterone measures have been proposed to estimate FT from either additional assay steps or calculations using total testosterone (TT) and sex hormone-binding globulin (SHBG) measured in the same sample. However, none have been critically validated in large numbers of blood samples. METHODS: We analyzed a large dataset comprising over 4000 consecutive blood samples in which FT as well as TT and SHBG were measured. Dividing the dataset into samples with blood TT above and below 5 nM, using a bootstrap regression modeling approach guided by Akaike Information Criterion for model selection to balance parsimony against reduction of residual error, empirical equations were developed for FT in terms of TT and SHBG. RESULTS: Comparison between the empirical FT equations with the laboratory FT measurements as well as three widely used calculated FT methods showed the empirical FT formulae had superior fidelity with laboratory measurements while previous FT formulae overestimated and deviated systematically from the laboratory FT values. CONCLUSION: We conclude that these simple, assumption-free empirical FT equations can estimate accurately blood FT from TT and SHBG measured in the same samples with the present assay methods and have suitable properties for wider application to evaluate the clinical utility of blood FT measurements.     

The aging male: testosterone deficiency and testosterone replacement. An up-date

The significance of the age-related decline of androgens remains unclear in terms of cardiovascular risk, mood and cognition, and prostatic health. Although much research has been undertaken in this area and men's health has received still more attention in the latest years, there are no data based on randomized controlled clinical studies in aging men investigating the long-term effects of androgen replacement therapy on various aspects of the cardiovascular system, the immune system, body composition, and the brain. In men receiving long-term androgen replacement therapy, the safety aspects regarding the prostate are also an area of clinical importance. In this paper we present an up-dated review of the experimental and clinical evidence of androgen deficiency and androgen replacement therapy on carbohydrate metabolism, on coagulation and fibrinolysis, inflammatory effects, effects on lipoprotein metabolism, direct arterial effects, effects on body composition, effects on cognitive function and mood, and prostatic effects. The evidence clearly shows that data for the most part are conflicting, with only very few randomized studies available.     

Radioimmunoassay of serum LH and testosterone in male rabbits actively immunized against testosterone.

Five male rabbits were actively immunized against testosterone to determine if this procedure could permanently inactivate circulating testosterone. To assess the response to immunization, serum LH, serum testosterone and antitestosterone titer (titer) were measured by radioimmunoassay at various times after immunization. All rabbits produced antisera to testosterone and developed serum LH levels similar to those measured in castrated males. The rise in serum LH was particularly pronounced after a booster immunization but these elevated levels were not maintained which suggests that biological neutralization was only transient. Serum testosterone rose dramatically after immunization and was directly correlated with titer. High serum testosterone concentrations were associated with both high and low serum LH. No correlation existed between titer ans serum LH. It is concluded that active immunization against testosterone does not necessarily result in a permanent neutralization of circulating testosterone and that titer alone is an inadequate criterion of neutralization.     

Saliva and serum testosterone following oral testosterone undecanoate administration in normal and hypogonadal men

Since saliva testosterone reflects the testosterone fraction available to target tissues the therapeutic effectiveness of orally administered testosterone undecanoate was assessed by measuring testosterone in serum and saliva. Matched saliva and serum samples were obtained from 12 normal men and 8 hypogonadal men before and at hourly intervals after the oral administration of 120 mg testosterone undecanoate. The test was repeated in 3 men after they had taken 40 mg testosterone undecanoate twice daily for 4 to 5 weeks. Following testosterone undecanoate administration serum and saliva testosterone always showed parallel increases. However, the absorption curves showed a high interindividual variability in the time when maximum concentrations were reached, as well as in the maximum levels themselves. The increases in serum and saliva testosterone were similar in normal and hypogonadal men. In normal men basal levels were reached 4 h after the maximum had occurred, while in hypogonadal men testosterone levels were not different from basal levels 2 h after the maximum. The study shows that testosterone undecanoate is well absorbed from the gut and releases significantly elevated amounts of testosterone which is available to target tissues. As the absorption pattern was always parallel in both fluids, hydrolysis of the circulating testosterone ester by the tissue itself seems to effect no additional increase of testosterone in the tissue.     

Free testosterone index: comparison with plasma free testosterone

Blood-free testosterone indices were measured among 28 normal men (age; 24-48 yrs.), 20 normal women (20-36 yrs.), 18 pregnant women (22-31 yrs.), 17 males with hypogonadism (23-56 yrs.), 17 males with chronic hepatitis (20-42 yrs.), 24 males with liver cirrhosis (29-68 yrs.), 34 males with hyperthyroidism (20-42 yrs.) and 7 hirsute women (18-31 yrs.), and these were compared with the plasma concentrations of free testosterone. The testosterone index was obtained by multiplying the plasma concentration of testosterone by the percent of sex hormone-binding globulin (SHBG), non-bound testosterone precipitated by dextran-coated charcoal. A significant increase of plasma testosterone was observed in patients with chronic hepatitis (p less than 0.001) and hyperthyroidism (p less than 0.001) as compared with normal men and was also observed in pregnant (p less than 0.01) and hirsute women (p less than 0.01) as compared with normal women. The close negative correlation between plasma levels of testosterone and the percent of SHBG non-bound testosterone (r = -0.87, n = 79, p less than 0.001) was observed among normal men, male patients with chronic hepatitis and hyperthyroidism. The sex hormone binding capacity was increased from two to three fold in patients with chronic hepatitis and hyperthyroidism. The patients with compensated liver cirrhosis had increased plasma testosterone and a decreased percent of SHBG non-bound testosterone, and those with decompensated liver cirrhosis had decreased plasma testosterone and a normal percent of SHBG non-bound testosterone. The plasma concentration of free testosterone was normal in patients with chronic hepatitis and hyperthyroidism. It decreased in pregnancy (p less than 0.01) and increased in hirsute women (p less than 0.01). The blood free testosterone index was slightly high in one third of the patients with chronic hepatitis and hyperthyroidism as compared with that in normal men. However, a close correlation of the percent of SHBG non-bound testosterone and fractional free testosterone (%) measured by equilibrium dialysis (gamma = 0.82, p less than 0.001) was obtained in all subjects (n = 170). These data suggest that the blood free testosterone index parallels the plasma concentration of free testosterone and is useful to evaluate the status of androgenicity.     

Prenatal testosterone and gender-related behaviour

Testosterone plays an important role in mammalian brain development. In neural regions with appropriate receptors testosterone, or its metabolites, influences patterns of cell death and survival, neural connectivity and neurochemical characterization. Consequently, testosterone exposure during critical periods of early development produces permanent behavioural changes. In humans, affected behaviours include childhood play behaviour, sexual orientation, core gender identity and other characteristics that show sex differences (i.e. differ on average between males and females). These influences have been demonstrated primarily in individuals who experienced marked prenatal hormone abnormalities and associated ambiguities of genital development (e.g. congenital adrenal hyperplasia). However, there is also evidence that testosterone works within the normal range to make some individuals within each sex more sex-typical than others. The size of testosterone-related influences, and perhaps even their existence, varies from one sex-typed characteristic to another. For instance: prenatal exposure to high levels of testosterone has a substantial influence on sex-typical play behaviour, including sex-typed toy preferences, whereas influences on core gender identify and sexual orientation are less dramatic. In addition: there appears to be little or no influence of prenatal testosterone on mental rotations ability, although mental rotations ability shows a marked sex difference. These findings have implications for basic understanding of the role of testosterone in normative gender development, as well as for the clinical management of individuals with disorders of sex development (formerly called intersex syndromes).     

睾酮与脑卒中

睾酮是人类最重要的内分泌激素之一,与人类许多重要的生理、病理生理调节过程有关。近年研究发现,睾酮与脑卒中许多危险因素有关。如睾酮可加剧高血压的发展,可促进高血压性肾损害;睾酮可通过影响脂质代谢参与动脉粥样硬化的形成;可导致胰岛素抵抗的发生发展;还可加重脑卒中后脑损伤;并可能与肺损伤的发生机制有关。本文对近年有关睾酮与脑卒中及脑卒中后器官损伤的研究进展作一综述。     

Acutely administered ethanol participates in testosterone synthesis and increases testosterone in rat brain

BACKGROUND: The interaction of alcohol and testosterone has long been of interest, mainly due to the effect of alcohol on aggression and sexual behavior. To date, there have been very few, if any, studies examining the effect of acute alcohol administration on testosterone concentrations in the brain. The administration of 1,1-dideuteroethanol ([1,1-2H2]ethanol) provided the opportunity to trace the deuterium label into newly synthesized deuterotestosterone in brain samples to determine whether ethanol oxidation was directly linked to testosterone synthesis. METHODS: Unoperated and adrenalectomized-gonadectomized (ADX/GDX) rats were given either ethanol or [1,1-2H2]ethanol in a single intraperitoneal dose of 2 g/kg body weight. We used gas chromatography/mass spectrometry to accurately determine both the amount of steroids present and the degree of deuterium incorporation into specific steroids isolated from brain samples. RESULTS: Thirty minutes after alcohol administration, the level of total testosterone increased 4-fold in the frontal cortex and 3-fold in the plasma of unoperated male Wistar rats. The relative increase in the abundance of monodeuterated testosterone 30 min after [1,1-2H2]ethanol administration was significant (p < 0.05) in both brain and plasma. ADX/GDX animals treated with alcohol had testosterone concentrations that were 5% of those found in unoperated animals dosed with ethanol. CONCLUSIONS: Acutely administered ethanol increased brain concentrations of testosterone 4-fold in male Wistar rats. ADX/GDX surgery reduced brain concentrations of testosterone in response to alcohol by 95%. The deuterium labeling of testosterone after [1,1-2H2]ethanol showed that ethanol oxidation is directly linked to testosterone biosynthesis and that the deuterium-labeled testosterone is present in the central nervous system. These results demonstrate that peripherally administered ethanol directly contributes to the concentrations of testosterone in the central nervous system and that the testosterone found in brain samples is primarily synthesized in the periphery. These findings may be important for understanding the behavioral changes associated with acute alcohol consumption.     

Serum testosterone and bioavailable testosterone correlate with age and body size in hypogonadal men treated with testosterone undecanoate (1000 mg IM--Nebido)

Objective To investigate the loading regimen for intramuscular (IM) testosterone undecanoate (Nebido®) to determine whether testosterone and bioavailable testosterone levels achieved correlate with age or body size of subjects studied. Design Retrospective observational study of testosterone naïve patients and patients previously treated with an alternative testosterone therapy. Patients 51 hypogonadal men (35, 68·6% secondary hypogonadism). 8 (16%) had not previously received testosterone therapy. Measurements Patients received an IM injection of Nebido (1000 mg) at baseline and a second injection after 6 weeks. Serum was assayed at baseline and 18 weeks after commencing Nebido for total testosterone (TT) and SHBG. Bioavailable testosterone was calculated (cBioT) using TT and SHBG. Measurements were taken for weight, body mass index (BMI) and body surface area (BSA). Results Baseline TT (mean 11·5 nmol/l, range 0·3–54·8) increased by 50% after commencing Nebido (17·2 nmol/l (5·4–32·8), P = 0·0001). 75% of subjects had a TT within the reference range (8·0–25·0 nmol/l). Subjects with primary hypogonadism had a higher 18‐week TT [20·9 nmol/l (9·8–32·8) vs. 15·5 (5·4–32·6), P = 0·02] and SHBG [39·2 nmol/l (11–82) vs. 25·7 (9·0–60·0), P = 0·003] although the cBioT was not significantly different [4·9 nmol/l (2·9–7·3) vs. 4·2 (2·0–7·9), P = 0·12]. The 18‐week TT positively correlated with age (R = 0·36, P = 0·01) and negatively correlated with weight (R = –0·38, P = 0·006), BMI (R = –0·42, P = 0·002) and BSA (R =–0·38, P = 0·007). Similarly cBioT correlated with age (R = 0·28, P = 0·04), weight (R = –0·29, P = 0·03), BMI (R = –0·30, P = 0·03) and BSA (R = –0·27, P = 0·05). Age (t = 2·04, P = 0·05) and baseline testosterone (t = –9·26, P < 0·0001) were independent variables of the increase in TT at 18 weeks. Conclusion This starting regimen is simple and provides the majority of men with a TT within the reference range. Age and baseline TT are independent variables of the increase in TT with IM testosterone undecanoate. At week 18 age and body size correlated with the cBioT and TT and this may then be used to estimate dosing frequency for this therapy.     

Salivary testosterone in hirsutism: correlations with serum testosterone and the degree of hair growth

Testosterone (T) concentrations in saliva and serum were measured in 53 women with various degrees of hirsutism and hyperandrogenism. The bioavailability of T was judged by comparing the correlations among the grade of hirsutism, salivary testosterone (SaT), and serum total and free T (fT) and sex hormone-binding globulin (SHBG) levels. The effect of body mass index on the correlations was also studied. The high SaT concentrations [mean, 237.6 +/- 66.7 (+/- SD) pmol/L] compared to the serum fT concentrations (mean, 29.1 +/- 11.8 pmol/L) in hirsute women may reflect the bioavailability of albumin-bound T or an ability of the salivary glands to metabolize steroids. SaT was more closely related to the T/SHBG ratio (mean, 82.5 X 10(-3) +/- 54.8), reflecting the non-SHBG-bound fraction of T, than to serum fT, which might support the former theory. SaT correlated better to the degree of hirsutism (rho = 0.45; P less than 0.01) than did any of the serum T parameters or SHBG. The correlation between SaT and hirsutism was partly dependent on the effect of body mass index. After eliminating this effect, SaT still correlated with hair growth on the total body area (rho = 0.36; P less than 0.05). On the basis of the results, SaT seems to relate to the bioavailable fraction of the hormone and, thus, appears to be an optimal method for studying hirsute women.