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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↗

PubMed1986

[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.

Adult↗

PubMed2001

Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels.

BACKGROUND: A large proportion of men over 65 years of age have bioavailable testosterone levels below the reference range of young adult men. The impact of this on musculoskeletal health and the potential for improvement in function in this group with testosterone supplementation require investigation. METHODS: Sixty-seven men (mean age 76 +/- 4 years, range 65--87) with bioavailable testosterone levels below 4.44 nmol/l (lower limit for adult normal range) were randomized to receive transdermal testosterone (two 2.5-mg patches per day) or placebo patches for 1 year. All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones (testosterone, bioavailable testosterone, sex-hormone binding globulin [SHBG], estradiol, and estrone), bone mineral density (BMD; femoral neck, Ward's triangle, trochanter, lumbar spine, and total body), bone turnover markers, lower extremity muscle strength, percent body fat, lean body mass, hemoglobin, hematocrit, prostate symptoms, and prostate specific antigen (PSA) levels. RESULTS: Twenty-three men (34%) withdrew from the study; 44 men completed the trial. In these men, bioavailable testosterone levels increased from 3.2 +/- 1.2 nmol/l (SD) to 5.6 +/- 3.5 nmol/l (p <.002) at 12 months in the testosterone group, whereas no change occurred in the control group. Although there was no change in estradiol levels in either group, estrone levels increased in the testosterone group (103 +/- 26 pmol/l to 117 +/- 33 pmol/l; p <.017). The testosterone group had a 0.3% gain in femoral neck BMD, whereas the control group lost 1.6% over 12 months (p =.015). No significant changes were seen in markers of bone turnover in either group. Improvements in muscle strength were seen in both groups at 12 months compared with baseline scores. Strength increased 38% (p =.017) in the testosterone group and 27% in the control group (p =.06), with no statistical difference between the groups. In the testosterone group, body fat decreased from 26.3 +/- 5.8% to 24.6 +/- 6.5% (p =.001), and lean body mass increased from 56.2 +/- 5.3 kg to 57.2 +/- 5.1 kg (p =.001), whereas body mass did not change. Men receiving testosterone had an increase in PSA from 2.0 +/- 1.4 microg/l to 2.6 +/- 1.8 microg/l (p =.04), whereas men receiving placebo had an increase in PSA from 1.9 +/- 1.0 microg/l to 2.2 +/- 1.5 microg/l (p =.09). No significant differences between groups were seen in hemoglobin, hematocrit, symptoms or signs of benign prostate hyperplasia, or PSA levels. CONCLUSIONS: Transdermal testosterone (5 mg/d) prevented bone loss at the femoral neck, decreased body fat, and increased lean body mass in a group of healthy men over age 65 with low bioavailable testosterone levels. In addition, both testosterone and placebo groups demonstrated gains in lower extremity muscle strength, possibly due to the beneficial effects of vitamin D. Testosterone did result in a modest increase in PSA levels but resulted in no change in signs or symptoms of prostate hyperplasia.

Administration, Cutaneous↗

PubMed1983

Testosterone concentrations in human seminal plasma and saliva and its correlation with non-protein-bound and total testosterone levels in serum.

A sensitive, specific and precise non-chromatographic method for the radioimmunoassay of testosterone in human seminal plasma and saliva from adult and pubertal males is described, and the values compared to total and non-protein-bound testosterone levels in serum. There was a significant correlation between salivary and serum-free levels of testosterone (r = 0.75, P less than 0.001, n = 67) whilst the correlation of serum levels of total testosterone with free as well as with salivary testosterone levels was weaker (r = 0.63 and 0.64, respectively). The salivary and serum levels of free testosterone showed better correlation with the stage of puberty than did the serum levels of total testosterone. Further evidence for a correlation between salivary and serum levels of free testosterone was obtained following oral administration of testosterone undecanoate, as this treatment increased the mean concentration of serum total testosterone after 3 h by 82%, but increased salivary and serum levels of free testosterone by only 30% and 20%, respectively. The coefficient of correlation between serum levels of total testosterone and seminal plasma testosterone was 0.73 (P less than 0.001), whilst the correlation between levels of serum-free testosterone with both salivary and seminal plasma levels of testosterone was statistically non-significant. Our observations on salivary testosterone are in accordance with the diffusion of non-protein-bound steroids into peripheral tissues, and consequently into their secretions. This model, however, does not appear to be applicable to the sex accessory glands.

Adolescent↗

PubMed1998

Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels.

Although weight loss associated with human immunodeficiency virus (HIV) infection is multifactorial in its pathogenesis, it has been speculated that hypogonadism, a common occurrence in HIV disease, contributes to depletion of lean tissue and muscle dysfunction. We, therefore, examined the effects of testosterone replacement by means of Androderm, a permeation-enhanced, nongenital transdermal system, on lean body mass, body weight, muscle strength, health-related quality of life, and HIV-disease markers. We randomly assigned 41 HIV-infected, ambulatory men, 18-60 yr of age, with serum testosterone levels below 400 ng/dL, to 1 of 2 treatment groups: group I, two placebo patches (n = 21); or group II, two testosterone patches designed to release 5 mg testosterone over 24 h. Eighteen men in the placebo group and 14 men in the testosterone group completed the 12-week treatment. Serum total and free testosterone and dihydrotestosterone levels increased, and LH and FSH levels decreased in the testosterone-treated, but not in the placebo-treated, men. Lean body mass and fat-free mass, measured by dual energy x-ray absorptiometry, increased significantly in men receiving testosterone patches [change in lean body mass, +1.345 +/- 0.533 kg (P = 0.02 compared to no change); change in fat-free mass, +1.364 +/- 0.525 kg (P = 0.02 compared to no change)], but did not change in the placebo group [change in lean body mass, 0.189 +/- 0.470 kg (P = NS compared to no change); change in fat-free mass, 0.186 +/- 0.470 kg (P = NS compared to no change)]. However, there was no significant difference between the 2 treatment groups in the change in lean body mass. The change in lean body mass during treatment was moderately correlated with the increment in serum testosterone levels (r = 0.41; P = 0.02). The testosterone-treated men experienced a greater decrease in fat mass than those receiving placebo patches (P = 0.04). There was no significant change in body weight in either treatment group. Changes in overall quality of life scores did not correlate with testosterone treatment; however, in the subcategory of role limitation due to emotional problems, the men in the testosterone group improved an average of 43 points of a 0-100 possible score, whereas those in the placebo group did not change. Red cell count increased in the testosterone group (change in red cell count, +0.1 +/- 0.1 10(12)/L) but decreased in the placebo group (change in red cell count, -0.2 +/- 0.1 10(12)/L). CD4+ and CD8+ T cell counts and plasma HIV copy number did not significantly change during treatment. Serum prostate-specific antigen and plasma lipid levels did not change in either treatment group. Testosterone replacement in HIV-infected men with low testosterone levels is safe and is associated with a 1.35-kg gain in lean body mass, a significantly greater reduction in fat mass than that achieved with placebo treatment, an increased red cell count, and an improvement in role limitation due to emotional problems. Further studies are needed to assess whether testosterone supplementation can produce clinically meaningful changes in muscle function and disease outcome in HIV-infected men.

Absorptiometry, Photon↗

PubMed1997

Testosterone-induced susceptibility to Plasmodium chabaudi malaria: persistence after withdrawal of testosterone.

Testosterone induces susceptibility to Plasmodium chabaudi malaria by imposing restrictions on those mechanisms which mediate resistance controlled by genes of the H-2 complex and the non-H-2 background in mice. This study investigated whether these restrictions are abolished after withdrawal of testosterone. Female mice of the inbred strain C57BL/10 were treated with 0.9 mg testosterone twice a week for 3 weeks and testosterone was then withdrawn for 12 weeks. The treatment raised plasma testosterone levels from 0.18 ng/ml to 3.79 ng/ml. After the testosterone treatment, these levels progressively dropped and reached 0.21 ng/ml by week 12 after testosterone withdrawal. Surprisingly, however, the testosterone-induced susceptibility still persisted. When mice were challenged on week 12 after testosterone withdrawal, P. chabaudi infections were still fatal in testosterone-treated mice, in contrast to self-healing infections in resistant, i.e. untreated, control mice. In addition, testosterone caused a persistent decrease in the levels of total IgG antibodies, especially IgG1 and IgG2b isotypes. In contrast, testosterone-induced changes in spleen cells, such as the reduction in number by 50%, the relative increase in CD8+ cells and the decrease in Ig+ cells, as well as the acquisition of the susceptible phenotype, were completely reversed on week 10 after testosterone withdrawal at the latest. Testosterone did not affect the production of the TH1-signalling cytokine interferon-gamma and the TH2-signalling cytokines interleukin (IL)-4 and IL-10 in response to P. chabaudi malaria. Together, our data indicated that the gene-controlled host resistance to P. chabaudi malaria is subject to superior hormonal imprinting: when once induced by testosterone, mechanisms which suppress resistance thus causing susceptibility persist independently of testosterone.

Animals↗

PubMed2002

Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels.

BACKGROUND: Many men older than 50 years have bioavailable testosterone levels below the reference range for young adult men. The impact of the decreased androgen levels on cognition and health perception has received little attention. METHODS: Sixty-seven men (mean age 76 +/- 4 years, range 65-87) with bioavailable testosterone levels below 128 ng/dl (lower limit for adult normal range) were randomized to receive transdermal testosterone (2-2.5 mg patches/d) or placebo patches for 1 year. All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones [testosterone, bioavailable testosterone, sex hormone binding globulin (SHBG), estradiol, and estrone], cognitive tests (Digit Symbol, Digit Span, Trailmaking A and B), health perception (Medical Outcome Survey Short-form 36 or SF-36), lower extremity muscle strength and power, and calcium intake. RESULTS: Twenty-three men (34%) withdrew from the study; 44 men completed the trial. Bioavailable testosterone levels increased from 93 +/- 34 (SD) to 162 +/- 100 ng/dl (p <.002) at 12 months in the testosterone group (n = 24) while no change occurred in the control group (n = 20). While there was no change in estradiol levels in either group, estrone levels increased in the testosterone group (28 +/- 7 to 32 +/- 9 pg/dl, p =.017). Scores on the Digit Symbol test improved in both the testosterone and placebo groups. Scores on Trailmaking B improved in men treated with testosterone (p <.005), although the changes were not statistically different from the changes seen in the placebo group. Twelve-month scores on Trailmaking B for the entire group were correlated with 12-month testosterone levels (p =.016). Scores for health perception measured by SF-36 did not change significantly, though scores of mental and general health declined in both groups during the 12-month intervention. Twelve-month bioavailable testosterone scores were directly correlated with scores for physical role (p =.022), vitality (p =.036), and the physical composite score (p =.010). CONCLUSIONS: Transdermal testosterone treatment in men with low bioavailable testosterone levels does not impair and may improve cognitive function. Treatment did not improve health perception but this may have been due to the side effects of skin irritation suggested by similar reactions in both the testosterone and placebo groups.

Administration, Cutaneous↗

PubMed2000

The contribution of hepatic inactivation of testosterone to the lowering of serum testosterone levels by ketoconazole.

Hepatic biotransformation processes can be modulated by chemical exposure and these alterations can impact the biotransformation of endogenous substrates. Furthermore, chemically mediated alterations in the biotransformation of endogenous steroid hormones have been implicated as a mechanism by which steroid hormone homeostasis can be disrupted. The fungicide ketoconazole has been shown to lower serum testosterone levels and alter both gonadal synthesis and hepatic inactivation of testosterone. The present study examined whether the effects of ketoconazole on the hepatic biotransformation of testosterone contribute to its lowering of serum testosterone levels. Results also were used to validate further the use of the androgen-regulated hepatic testosterone 6alpha/15alpha-hydroxylase ratio as an indicator of androgen status. Male CD-1 mice were fed from 0 to 160 mg/kg ketoconazole in honey. Four h after the initial treatment, serum testosterone levels, gonadal testosterone secretion, and hepatic testosterone hydroxylase activity decreased, and the hepatic testosterone 6alpha/15alpha-hydroxylase ratio increased in a dose-dependent manner. Immunoblot analysis indicated that the transient decline in hepatic biotransformation was not due to reduced P450 protein levels. Rather, hepatic testosterone biotransformation activities were found to be differentially susceptible to direct inhibition by ketoconazole. Differential inhibition was also responsible for the increase seen in the 6alpha/15alpha-hydroxylase ratio. The changes in serum testosterone levels could be explained by decreased gonadal synthesis of testosterone and were not impacted by decreased hepatic biotransformation of testosterone. These results demonstrate that changes in the hepatic hydroxylation of testosterone by ketoconazole, and perhaps other chemicals, have little or no influence serum testosterone levels.

Animals↗

PubMed2003

Transdermal testosterone delivery: testosterone patch and gel.

Testosterone replacement treatment is usually life-long. Fortunately, testosterone administration is relatively safe and until the age of 50 years few side effects are noted with normal doses of testosterone. After the age of 50 years when prostate disease becomes more prevalent, shorter-acting testosterone preparations, allowing a fast reduction of circulating testosterone levels, may be an advantage. Testosterone has an impact on sexual and non-sexual behaviour and short-acting testosterone preparations may be better suited for the initiation of long-term administration allowing the monitoring of behavioural effects. Testosterone can be delivered to the circulation through the intact skin, both genital and non-genital. Transdermal administration delivers testosterone at a controlled rate into the systemic circulation, avoiding hepatic first pass and reproducing the diurnal rhythm of testosterone secretion and without the peak and trough levels observed with the use of the traditional long-acting testosterone injections. In conclusion, both the testosterone patch and testosterone gel are valuable contributions to androgen replacement treatment meeting the requirements specified for testosterone replacement treatment.

Administration, Cutaneous↗

PubMed1987

Amniotic fluid testosterone and testosterone glucuronide levels in the determination of foetal sex.

Unconjugated testosterone levels were assayed in 351 amniotic fluid samples obtained at 15-19 weeks gestation. The median values for unconjugated testosterone in the 166 female foetuses and 185 male foetuses were 137 and 712 pmol/l respectively. Sixteen amniotic fluid samples from male foetuses had unconjugated testosterone levels lower than the highest female unconjugated testosterone value (361 pmol/l). Testosterone glucuronide was measured in amniotic fluid from 48 female and 55 male foetuses. There was a significant sex difference in the median values of testosterone glucuronide between female (median 160 pmol/l, range 64-465 pmol/l) and male (median 817 pmol/l, range 68-3707 pmol/l) amniotic fluid specimens (P less than 0.001). Of the sixteen male foetuses with amniotic fluid unconjugated testosterone levels in the female range, 12 had amniotic fluid testosterone glucuronide levels within the male testosterone glucuronide range of values. Hence used in conjunction with unconjugated testosterone, testosterone glucuronide increased the predictive accuracy of foetal sexing from 95.4 to 98.9%. Testosterone sulphate was measured in 24 female and 25 male amniotic fluid samples. There was no Testosterone sulphate was measured in 24 female and 25 male amniotic fluid samples. There was no significant difference between female (median 2591 pmol/l) and male (median 2964 pmol/l) testosterone sulphate levels.

Amniocentesis↗

PubMed1983

Distribution of testosterone in plasma proteins during replacement therapy with testosterone enanthate in patients suffering from hypogonadism.

In five hypogonadal men treated with 250 mg of testosterone enanthate once every three weeks, total testosterone, "free" testosterone and the percent of testosterone bound to the sex hormone-binding globulin (SHBG) and albumin were determined during three weeks. Immediately after the injection total plasma testosterone rapidly increased about four times the starting level closely paralleled by the concentration of "free" testosterone. We found that if the concentration of SHBG had been reached albumin took over the surplus of the testosterone. Whereas in the first and second week after the injection, high and sufficient levels of testosterone were determined, both total and "free" testosterone approached the lower limit of the normal male range in the third week, i.d. 300 ng/dl, or 5 ng/dl, respectively. In one patient with hypalbuminemia, "free" testosterone decreased during the third week below 3 ng/dl though his total testosterone remained sufficient high. This patient complained about symptoms of androgen deficiency. We explained this with his impaired capacity to bind the excess of testosterone by albumin. We concluded that though the concentration of total testosterone may be sufficient high, "free" testosterone can decrease to very low levels due to disturbance in the distribution of the androgen between the plasma proteins.

Adolescent↗

PubMed1993

Spontaneous gonadotropin and testosterone concentration profiles in prepubertal and pubertal boys: temporal relationship between luteinizing hormone and testosterone.

To investigate the detailed pattern of change in circulating gonadotropin and testosterone concentrations around the onset of puberty and to determine the temporal relationship between the gonadotropin and testosterone secretion, plasma gonadotropin and testosterone were measured at 20-min intervals for 24 h in 21 normal short boys. The obtained plasma hormone concentrations were analyzed by Cluster pulse detection algorithm, cosinor analysis, and cross-correlation analysis. The 21 subjects were divided into the prepubertal (n = 16) and early pubertal (n = 5) groups. All subjects showed nocturnal LH and FSH pulses and had significant circadian LH and FSH rhythms. Except for six boys of prepubertal group, all subjects showed nocturnal testosterone pulses and had significant circadian testosterone rhythms. The acrophase (clocktime of maximal value) of circadian testosterone rhythm was 0308-0428 h. Cross-correlation analysis demonstrated significant positive cross-correlations between LH and testosterone that were maximum at a testosterone lag of 60-120 min. Further, to eliminate intrinsic autocorrelations within the LH and testosterone time series, we filtered the data before subjecting them to the cross-correlation analysis. As a result, significant positive cross-correlations were found at a testosterone lag of 40 min in 10 peripubertal boys. We conclude that testosterone concentration profiles are pulsatile and show marked circadian rhythm well before the onset of puberty. LH and testosterone time series are significantly coupled when testosterone lags LH by about 40 min. This time lag might correspond to the time for synthesizing and secreting testosterone in Leydig cells after binding of LH to the Leydig cell receptors.

Adolescent↗

PubMed1983

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.

Adolescent↗

PubMed1983

Testosterone concentration in plasma and its production in the testes of the rat following testosterone, oestradiol and HCG application.

The authors present data on the effect of a seven-day application of testosterone, oestradiol and HCG to male rats, on plasma concentration and testicular production of testosterone. In addition, they also studied the in vitro effect of LH on testosterone production in control male rats and rats treated with testosterone, oestradiol and HCG. Plasma testosterone concentration was higher in animals treated with testosterone and HCG (exogenous effect) than in the control group. Oestradiol-treated males had a markedly lowered plasma concentration of testosterone. A striking decline in testosterone production was noted in the testes of male rats receiving testosterone and oestradiol in comparison with the controls. Testosterone production failed to increase even after LH had been added to the incubation medium. A maximum testosterone production in the testes was achieved following HCG application. Testosterone concentration in plasma and in incubates was determined by radioimmunoassay. On the basis of the results, the authors suggest the significance of sex hormones and their effect on the mechanisms controlling testosterone production in the testicular gland. Control of testosterone production takes place not solely in the hypothalamo-hypophyseal system, but to a great extent also at the cellular level of the sex gland itself.

Animals↗

PubMed1984

Salivary testosterone levels in normal and testosterone treated monkeys.

Testosterone concentrations in saliva and matched serum samples were measured by radioimmunoassay, in normal and testosterone treated adult male cynomolgus monkeys (Macaca fascicularis) and in untreated rhesus monkeys (Macaca mulatta). Saliva and serum samples were collected under ketamine anaesthesia. In 4 cynomolgus monkeys, the mean basal testosterone levels were 195 +/- 22 pmol/l in saliva and 24 +/- 2 nmol/l in serum (n = 17). The salivary testosterone corresponded to 0.9 +/- 0.1% of the serum testosterone concentration. In 5 rhesus monkeys the mean testosterone concentrations were 147 +/- 10 pmol/l in saliva and 17 +/- 2 nmol/l in matched serum samples with a percent ratio of 1.6 +/- 0.3 (n = 15). Following a single i.m. injection of 50 mg testosterone propionate to 4 monkeys, both salivary and serum testosterone levels increased promptly and in parallel. The salivary testosterone levels correlated well with the serum testosterone values. The study suggests that, as in the human, determination of salivary testosterone can be used as an index of free testosterone in this animal. Moreover, the monkey can be used as a model for studies in the human involving monitoring of salivary testosterone.

Animals↗

PubMed2003

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.

Animals↗