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At least 19 recordsLinked to original sources
PubMed1998

A time-resolved fluorescence immunoassay for the measurement of testosterone in saliva: monitoring of testosterone replacement therapy with testosterone buciclate.

Monitoring of testosterone replacement therapy requires a reliable method for testosterone measurement. Determination of salivary testosterone, which reflects the hormone's biologically active plasma fraction, is a superior technique for this purpose. The aim of the present study was to establish a new sensitive time-resolved fluorescence immunoassay for the accurate measurement of testosterone levels in saliva and to validate it by monitoring testosterone replacement therapy in eight hypogonadal men. A clinical phase I-study with the new ester testosterone buciclate was performed to search for new testosterone preparations to produce constant serum levels in the therapy of male hypogonadism. After two control examinations eight male patients with primary hypogonadism were randomly assigned to two treatment groups (n = 2 x 4) and given single doses of either 200 mg (group I) or 600 mg (group II) testosterone buciclate intramuscularly. Saliva and blood samples were obtained 1, 2, 3, 5 and 7 days post injection and then weekly for three months. The time-resolved fluorescence immunoassay for salivary testosterone shows a detection limit of 16 pmol/l, an intra-assay CV of 8.9% (at a testosterone concentration of 302 pmol/l), an inter-assay CV of 8.7% (at a testosterone concentration of 305 pmol/l) and a good correlation with an established radioimmunoassay of r = 0.89. The sample volume required by this method is only 180 microliters for extraction and duplicate determination. The assay procedure requires no more than three hours. In group I (200 mg) testosterone did not increase to normal levels either in saliva or in serum. However, in group II, androgen levels increased significantly and were maintained in the normal range for up to 12 weeks with maximal salivary testosterone levels of 303 +/- 18 pmol/l (mean +/- SE) and maximal testosterone levels of 13.1 +/- 0.9 nmol/l (mean +/- SE) in serum in study week 6 and 7. The time-resolved fluorescence immunoassay for salivary testosterone provides a useful tool for monitoring androgen status in men and women and is well suited for the follow-up of testosterone replacement therapy on an outpatient basis. The long-acting ester testosterone buciclate is a promising agent for substitution therapy of male hypogonadism and in combination with testosterone monitoring in saliva offers an interesting new perspective for male contraception.

Adult↗
PubMed1987

Total testosterone, free-androgen index, calculated free testosterone, and free testosterone by analog RIA compared in hirsute women and in otherwise-normal women with altered binding of sex-hormone-binding globulin.

We compared the clinical value of information on free testosterone as measured with the Coat-A-Count (Diagnostic Products Corp.) radioimmunoassay kit involving a ligand analog with that of total testosterone, the free-androgen index, and free testosterone calculated from concentrations of testosterone, sex-hormone-binding globulin, and albumin, in hirsute women, pregnant women, oral-contraceptive users, women with thyroid disease, and epileptic women taking phenytoin. Total testosterone, the free-androgen index, calculated free testosterone, and free testosterone by RIA were increased in 41-68% of hirsute women. Values for free testosterone increased in the first and third trimesters of pregnancy but remained within normal limits in all non-hirsute groups. Total testosterone was increased in patients having increased sex-hormone-binding globulin, whereas the free-androgen index and, to a lesser extent, calculated free testosterone were significantly decreased. Free testosterone measured by analog RIA not only has greater diagnostic efficiency than total testosterone, it also is technically simpler to determine than the free-androgen index and calculated free testosterone.

Androgens↗
PubMed1999

Effects of long-term treatment with testosterone enanthate in rhesus monkeys: I. Pharmacokinetics of testosterone, testicular volume and liver metabolism of testosterone.

The effects of long-term administration of testosterone enanthate on the pharmacokinetics and bioavailability of testosterone were studied in adult male rhesus monkeys (n = 9), injected with 50 mg of testosterone enanthate (TE) once every 14 days for a total of 32 months. Control animals were injected with 0.2 mL olive oil. Serum testosterone levels increased sharply within 24 h of the first injection of TE and reached a peak on day 3 followed by a sharp decline, but baseline values were not reached even by day 14. Subsequent injections of TE caused a similar pharmacokinetic profile until the 55th injection; testosterone levels on day 3 declined from the 56 to 58th injection and remained in a lower range until the last injection. Repeated injections of TE increased the bioavailability of testosterone as shown by the Area Under the Curve. The nocturnal (22.00 h) surge in testosterone levels during the pretreatment phase was abolished by TE injections. TE injections altered the metabolism of testosterone by the liver, as studied in vitro; while liver from control animals converted testosterone to androstenedione as the major metabolite, androsterone was the major metabolite in chronically TE-treated animals. Spermatogenesis and the associated increase in testicular volume observed in control animals in winter were suppressed in TE-treated animals. The results indicate that repeated TE injections elevate serum testosterone to supra-physiological levels with marked fluctuations in circulating testosterone levels after each injection. Possibly in response to these elevated levels, there was a change in the metabolism of testosterone by the liver as observed in vitro.

Animals↗
PubMed1984

Comparative pharmacokinetics of testosterone enanthate and testosterone cyclohexanecarboxylate as assessed by serum and salivary testosterone levels in normal men.

The pharmacokinetics of 2 testosterone esters, testosterone enanthate and testosterone cyclohexanecarboxylate, were compared in a single blind crossover study in healthy young men. Their effects on serum and salivary levels of testosterone, as well as on the serum levels of LH, FSH and prolactin were measured after the injection of doses equivalent to 140 mg free testosterone. Both preparations yielded supraphysiological testosterone levels in serum and saliva as early as 2 h following injection, reaching peak levels 4 to 5 times above basal between 8 and 24 h. LH and FSH levels were suppressed as long as serum testosterone levels were elevated. Nine days after injecting testosterone enanthate and 7 days after giving testosterone cyclohexanecarboxylate, serum and salivary levels of testosterone had returned to basal. The longer activity of testosterone enanthate was also evidenced from more extended suppression of gonadotrophin levels. Although neither preparation is ideal because of the initial supraphysiological peaks, testosterone enanthate appears preferable for clinical use because of its slightly longer duration of action.

Adult↗
PubMed1997

Development of a time-resolved fluoroimmunoassay (TR-FIA) for testosterone: measurement of serum testosterone concentrations after testosterone treatment in the rainbow trout (Oncorhynchus mykiss).

A sensitive time-resolved fluoroimmunoassay (TR-FIA) for testosterone was developed, and the assay system was used for measuring serum testosterone concentrations in rainbow trout. Testosterone-3-(O-carboxymethyl)oxime-bovine serum albumin (T-3-CMO-BSA) was immobilized by physical adsorption to the wells of microtiter plates. A competitive assay using two antibodies was performed among T-3-CMO-BSA in the solid-phase, unknown amounts of testosterone, testosterone antibodies, and europium labeled secondary antibodies, followed by measurements using a time-resolved fluorometer (DELFIA system). The TR-FIA had a sensitivity of 0.075 pg/50 microliters sample (1.5 pg/ml), and the range of the assay system was between 1.5 pg/ml and 25 ng/ml. The intra- and interassay coefficients of variation for the testosterone TR-FIA were satisfactorily low, and were between 1.62 and 6.38% and 2.96 and 8.29%, respectively. The assay system was applied to measure the serum testosterone concentrations after an injection of testosterone dissolved in saline, propyleneglycol, or coconut oil. Among the three solvents, the coconut oil group showed continuously high serum testosterone level. In contrast, the saline and propyleneglycol groups had maximum concentrations 24 hr after the injection, but their levels were significantly lower than that of the coconut oil group. The testosterone TR-FIA method is sensitive, repeatable, and is as accurate as conventional RIAs. It is very good for measuring serum testosterone concentrations.

Animals↗
PubMed1975

[Androgen status of male diabetics. Total testosterone before and following stimulation with HCG, free testosterone, and testosterone binding capacity of patients with and without potency disorders].

In order to investigate the androgen status of diabetics we determined in 39 patients, 18-60 years old, 17 of which suffered from potency disturbances, the basal total plasma testosterone, the free testosterone fraction and the unbound plasma testosterone as well as the testosterone binding capacity. In 39 of these patients we proved the response of Leydig cells to HCG. Between normal persons and patients with and without potency disturbances basal total plasma testosterone did not differ significantly (p greater than 0.10). After a 3-day stimulation with HCG the increase of basal total plasma testosterone was significantly lower in the two diabetic groups in comparison with the normal persons (p less than 0.0005). The group with potency disturbances had significantly lower values for the free testosterone fraction (p less than 0.005) and unbound plasma testosterone (p less than 0.0025) than normal persons whereas diabetics without potency disturbances did not reveal any significant differences (p greater than 0.25 and p greater than 0.40). Further there were significant differences between the patients with and without potency disturbances (p less than 0.025) and (p less than 0.025). Testosterone binding capacity was significantly increased in the group with potency disturbances (p less than 0.0005) and also in the group without potency disturbances (p less than 0.01) as compared with controls. Moreover was it significantly higher in the group with potency disturbances than that without potency disturbances (p less than 0.01). For none of the parameters a functional correlation of age or diabetes duration could be demonstrated. The results are discussed with regard to the causes of potency disturbances in male diabetics.

Adolescent↗
PubMedDate not supplied

Absolute bioavailability of testosterone after oral administration of testosterone-undecanoate and testosterone.

The plasma levels of testosterone (T) were measured after oral administration of 25 mg T and 40 mg testosterone-undecanoate (TU) in a group of young women by a specific radioimmunoassay. Plasma levels were compared to those after intravenous administration of 1.5 micrograms testosterone/kg to another group of young women for determination of absolute bioavailability. Due to the high metabolic clearance rate of 24.5 ml/min/kg absolute systemic availability of free testosterone was calculated to 3.56 +/- 2.45%. Oral administration of testosterone undecanoate leads only to an absolute testosterone bioavailability of 6.83 +/- 3.32%.

Administration, Oral↗
PubMed1976

[Testosterone-binding capacity, free-plasma testosterone fraction, and free-plasma testosterone concentration in andrological patients (author's transl)].

Testosterone-binding capacity (TeBG), free-plasma testosterone fraction (%FT), and free-plasma testosterone concentration (AFT) were measured in 24 men with primary and 14 with secondary hypogonadism of various causes, as well as in eight with coital impotence. There was a highly significant correlation between TeBG and %FT (r = minus 0.891; P less than 0.0005). TeBG and %FT did not generally differ from normal in primary hypogonadism, while AFT was normal or decreased, depending on the corresponding whole testosterone concentrations. In secondary hypogonadism there was always an increased TeBG and decreased %FT. Depending on whole testosterone concentration, AFT was low or very low. In impotent subjects TeBG, %FT and AFT were generally normal. The role of AFT determination in andrological diagnosis is discussed.

Adolescent↗
PubMed1984

[The metabolism of testosterone in the central nervous system (1). Analysis of testosterone metabolites in the anterior pituitary and hypothalamus using gas chromatography-mass spectrometry (GC-MS), and subcellular localization of testosterone converting enzyme].

The aim of this study was to identify accurately the structure of testosterone metabolites in the anterior pituitary and hypothalamus for the investigation of the mechanism of androgen action in the central nervous system. Tissue homogenate and cellular fraction of male rat anterior pituitary and hypothalamus were incubated with testosterone-4-14C and testosterone-19-CD3 (14C/D3 = 1) in the presence of NADH and NADPH. The incubation media were extracted, and they were separated using thin layer chromatography (TLC). Using autoradiogram of TLC, four main radioactive fractions were found on the TLC. The TFA or TMS derivatives of every fraction were analyzed using GC-MS. The main metabolites in the anterior pituitary were identified as 5 alpha-androstan-17-ol 3-one; androst-4-ene-3, 17-dione, 5 alpha-androstane-3 alpha, 17 beta-diol, 5 alpha-androstane-3 beta, 17 beta-diol, androst-4-ene-3 alpha, 17 beta-diol and androst-4-ene-3 beta, 17 beta-diol. The result in the hypothalamus was the same as that in the pituitary. The subcellular localization of metabolites in the anterior pituitary was as follows: 5 alpha-androstan-17-ol-3-one, 5 alpha-androstane-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol were found in microsome; 5 alpha-androstane-3 alpha, 17 beta-diol and androst-4-ene-3 alpha, 17 beta-diol were found in soluble fraction. The result in the hypothalamus was the same as that in the pituitary.

Androstane-3,17-diol↗
PubMed2004

Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone.

Older men, particularly those with low serum testosterone (T) levels, might benefit from T therapy to improve bone mineral density (BMD) and reduce fracture risk. Concerns exist, however, about the impact of T therapy on the prostate in older men. We hypothesized that the combination of T and finasteride (F), a 5 alpha-reductase inhibitor, might increase BMD in older men without adverse effects on the prostate. Seventy men aged 65 yr or older, with a serum T less than 12.1 nmol/liter on two occasions, were randomly assigned to receive one of three regimens for 36 months: T enanthate, 200 mg im every 2 wk with placebo pills daily (T-only); T enanthate, 200 mg every 2 wk with 5 mg F daily (T+F); or placebo injections and pills (placebo). Low BMD was not an inclusion criterion. We obtained serial measurements of BMD of the lumbar spine and hip by dual x-ray absorptiometry. Prostate-specific antigen (PSA) and prostate size were measured at baseline and during treatment to assess the impact of therapy on the prostate. Fifty men completed the 36-month protocol. By an intent-to-treat analysis including all men for as long as they contributed data, T therapy for 36 months increased BMD in these men at the lumbar spine [10.2 +/- 1.4% (mean percentage increase from baseline +/- SEM; T-only) and 9.3 +/- 1.4% (T+F) vs. 1.3 +/- 1.4% for placebo (P < 0.001)] and in the hip [2.7 +/- 0.7% (T-only) and 2.2 +/- 0.7% (T+F) vs. -0.2 +/- 0.7% for placebo, (P < or = 0.02)]. Significant increases in BMD were seen also in the intertrochanteric and trochanteric regions of the hip. After 6 months of therapy, urinary deoxypyridinoline (a bone-resorption marker) decreased significantly compared with baseline in both the T-only and T+F groups (P < 0.001) but was not significantly reduced compared with the placebo group. Over 36 months, PSA increased significantly from baseline in the T-only group (P < 0.001). Prostate volume increased in all groups during the 36-month treatment period, but this increase was significantly less in the T+F group compared with both the T-only and placebo groups (P = 0.02). These results demonstrate that T therapy in older men with low serum T increases vertebral and hip BMD over 36 months, both when administered alone and when combined with F. This finding suggests that dihydrotestosterone is not essential for the beneficial effects of T on BMD in men. In addition, the concomitant administration of F with T appears to attenuate the impact of T therapy on prostate size and PSA and might reduce the chance of benign prostatic hypertrophy or other prostate-related complications in older men on T therapy. These findings have important implications for the prevention and treatment of osteoporosis in older men with low T levels.

Aged↗
PubMed2000

Short-term effects of intramuscular and transdermal testosterone on bone turnover, prostate symptoms, cholesterol, and hematocrit in men over age 70 with low testosterone levels.

The objective of the study was to determine whether short-term testosterone administration to older men with low bioavailable testosterone would have any immediate adverse effects, especially on the symptoms of benign prostate hyperplasia, preliminary to embarking on a long-term study of testosterone treatment. Transdermal and intramuscular testosterone were compared to determine whether there were any rapid changes in markers of bone formation or resorption with either testosterone administration. We undertook a non-randomized trial of 9 weeks intervention with either intramuscular testosterone, transdermal testosterone or neither followed by a 9-week observation period. Twenty-seven men over age 70 years with no medical conditions known to affect bone turnover and total testosterone levels below 350 ng/dl (normal range 350-1230 ng/dl) or bioavailable testosterone levels below 128 ng/dl (normal range 128-430 ng/dl) received either testosterone via transdermal patch (TP; two 2.5 mg patches/d), intramuscular testosterone enanthate (IM; 200 mg every 3 weeks) or no testosterone for 9 weeks of treatment followed by a 9 week observation period. Nine men were enrolled in each group. The mean age of the men was 74 +/- 3 years (range 70-83 years). While all men receiving testosterone treatment increased levels above their own baseline, only 6 of 9 men receiving transdermal testosterone achieved bioavailable testosterone levels in the normal range for young men. Neither treatment group demonstrated changes in estradiol levels. No side effects were reported using the intramuscular testosterone while 5/9 men using transdermal testosterone developed a rash. There were no significant changes in markers of bone resorption or formation in either testosterone treatment group. There were no ill effects on prostate size, symptoms or prostate specific antigen level. PSA levels of 1.5 +/- 0.7 ng/dl and 1.6 +/- 0.7 ng/dl in the TP and IM groups, respectively. were 2.0 +/- 1.0 ng/dl and 1.8 +/- 0.9 ng/dl following treatment. Cholesterol profiles were also not affected by either transdermal or intramuscular testosterone. Similarly hemoglobin and hematocrit remained unchanged in men receiving either testosterone preparation.

Administration, Cutaneous↗
PubMed2000

Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels.

CONTEXT: Previous studies of testosterone supplementation in HIV-infected men failed to demonstrate improvement in muscle strength. The effects of resistance exercise combined with testosterone supplementation in HIV-infected men are unknown. OBJECTIVE: To determine the effects of testosterone replacement with and without resistance exercise on muscle strength and body composition in HIV-infected men with low testosterone levels and weight loss. DESIGN AND SETTING: Placebo-controlled, double-blind, randomized clinical trial conducted from September 1995 to July 1998 at a general clinical research center. PARTICIPANTS: Sixty-one HIV-infected men aged 18 to 50 years with serum testosterone levels of less than 12.1 nmol/L (349 ng/dL) and weight loss of 5% or more in the previous 6 months, 49 of whom completed the study. INTERVENTIONS: Participants were randomly assigned to 1 of 4 groups: placebo, no exercise (n = 14); testosterone enanthate (100 mg/wk intramuscularly), no exercise (n = 17); placebo and exercise (n = 15); or testosterone and exercise (n = 15). Treatment duration was 16 weeks. MAIN OUTCOME MEASURES: Changes in muscle strength, body weight, thigh muscle volume, and lean body mass compared among the 4 treatment groups. RESULTS: Body weight increased significantly by 2.6 kg (P<.001) in men receiving testosterone alone and by 2.2 kg (P = .02) in men who exercised alone but did not change in men receiving placebo alone (-0.5 kg; P = .55) or testosterone and exercise (0.7 kg; P = .08). Men treated with testosterone alone, exercise alone, or both experienced significant increases in maximum voluntary muscle strength in leg press (range, 22%-30%), leg curls (range, 18%-36%), bench press (range, 19%-33%), and latissimus pulls (range, 17%-33%). Gains in strength in all exercise categories were greater in men assigned to the testosterone-exercise group or to the exercise-alone group than in those assigned to the placebo-alone group. There was a greater increase in thigh muscle volume in men receiving testosterone alone (mean change, 40 cm3; P<.001 vs zero change) or exercise alone (62 cm3; P = .003) than in men receiving placebo alone (5 cm3; P = .70). Average lean body mass increased by 2.3 kg (P = .004) and 2.6 kg (P<.001), respectively, in men who received testosterone alone or testosterone and exercise but did not change in men receiving placebo alone (0.9 kg; P = .21). Hemoglobin levels increased in men receiving testosterone but not in those receiving placebo. CONCLUSION: Our data suggest that testosterone and resistance exercise promote gains in body weight, muscle mass, muscle strength, and lean body mass in HIV-infected men with weight loss and low testosterone levels. Testosterone and exercise together did not produce greater gains than either intervention alone.

Adult↗