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Evidence that testosterone and follicular fluid do not interact in the control of FSH secretion in rams.

The hypothesis that testosterone and inhibin interact in the control of FSH secretion in rams was tested. Adult rams were castrated and were simultaneously given testosterone implants and 3-times daily sc injections of 0, 0.4, 0.8 or 1.6 ml charcoal-treated bovine follicular fluid (bFF). After 1 wk, the implants were removed, and the bFF injections continued as before. Blood samples were taken daily for mean LH, FSH and testosterone concentrations, and every 10 min for 12 h in the presence and in the absence of testosterone for assessment of pulsatile LH release. The bFF specifically inhibited FSH secretion from rat pituitary cells in culture. In the presence of testosterone, there were no main effects of bFF on mean plasma FSH or LH concentrations, nor were these values different from their pre-treatment means (P>0.05). Treatment with bFF did not affect LH pulse frequency or amplitude, but the number of rams showing LH pulses was reduced in the 0.8 and 1.6-ml dose groups (P<0.05). Removal of testosterone increased (P<0.05) both gonadotropins. In the absence of testosterone, no main effect of bFF on mean LH or FSH concentrations was observed, although the 1.6-ml dose suppressed the postcastration rise of both LH and FSH. These data suggest that inhibin does not interact with testosterone and that a physiological level of testosterone is sufficient for the regulation of FSH secretion in adult rams.

Journal Article↗

Heritability of testosterone levels in 12-year-old twins and its relation to pubertal development.

The aim of this study was to estimate the heritability of variation in testosterone levels in 12-year-old children, and to explore the overlap in genetic and environmental influences on circulating testosterone levels and androgen-dependent pubertal development. Midday salivary testosterone samples were collected on 2 consecutive days in a sample of 183 unselected twin pairs. Androgen-induced pubertal development was assessed using self-report Tanner scales of pubic hair development (boys and girls) and genital development (boys). A significant contribution of genetic effects to the variance in testosterone levels was found. Heritability was approximately 50% in both boys and girls. The remaining proportion of the variance in testosterone levels could be explained by nonshared environmental influences. The relatively high correlation between testosterone levels of opposite-sex dizygotic twins suggests that sex differences in genes influencing variation in testosterone levels have not yet developed in pre- and early puberty. Variance in pubertal development was explained by a large genetic component, moderate shared environmental influences, and a small nonshared environmental effect. Testosterone levels correlated moderately (r = .31) with pubertal development; the covariance between testosterone levels and pubertal development was entirely accounted for by genetic influences.

Child↗

Testosterone replacement in men with andropause: an overview.

Serum testosterone levels decline progressively as men age, with resulting pathophysiological changes. Because the onset of andropause is gradual and many of its symptoms mirror those associated with medications or disease states common in the elderly, a clinical diagnosis can be difficult to make. Additionally, because of a lack of established normal testosterone levels for different age groups, as well as confusion regarding what subset of testosterone to measure, simply testing testosterone levels is inadequate. Although clinical studies have shown testosterone supplementation to be safe, no long-term placebo-controlled trials have been performed. Among the possible side effects of testosterone replacement therapy is an increased risk of prostate cancer. While there is no evidence that supplemental testosterone will initiate prostate cancer or cause clinically significant progression of an established occult malignancy, the initial evaluation of patients prior to administration of testosterone requires screening for prostatic carcinoma. A number of formulations of testosterone are currently available; transdermal gels, although expensive, are the preferred modality because of their ease of administration.

Journal Article↗

Effects of testosterone on the rat renal medullary vasopressin receptor concentration and the antidiuretic response.

The renal concentrating ability declines with age in humans and animals. Studies suggest that the concentrating defect is due to a decrease in renal vasopressin sensitivity. With ageing, expression of the renal vasopressin V2 receptor in rat is impaired; the normal receptor expression is restored by testosterone treatment. The effect of testosterone on the renal sensitivity to vasopressin was investigated in young rats. Male rats after orchidectomy and chronic antiandrogen cyproterone acetate treatment, and female rats after chronic testosterone phenylpropionate treatment, were used. The plasma arginine-vasopressin (AVP) and testosterone concentrations, and the antidiuretic responses to AVP and the V2 agonist deamino-[8-D-arginine]-vasopressin (dDAVP) after volume loading were measured, and the renal [3H]AVP binding density was determined. The plasma AVP level decreased slightly, but not significantly, in male rats after orchidectomy and cyproterone acetate treatment, but did not alter in female rats after testosterone treatment. The AVP and dDAVP sensitivities decreased in male rats after orchidectomy and cyproterone acetate administration, and increased in female rats treated with testosterone, as compared with the animals with a normal gonadal function. [3H]AVP binding to the renal inner medullary membranes was decreased following orchidectomy or antiandrogen treatment in male rats, and increased in testosterone-treated female rats. The results suggest that testosterone may play a physiological role in maintenance of the V2 vasopressin receptor expression and hence in the normal urinary concentrating ability in rat.

Androgen Antagonists↗

Serum lipids in oophorectomized women during estrogen and testosterone replacement therapy.

OBJECTIVE: To evaluate the effects of giving testosterone undecanoate (TU) in addition to estrogen replacement on serum lipids in oophorectomized women. METHOD: Women with surgically induced menopause (n = 50) were randomly assigned to oral treatment with 2 mg of estradiol valerate in combination with 40 mg of TU or placebo for 24 weeks. The study was double-blind with cross-over to the other regimen for further 24 weeks of treatment. Forty-four women completed the study. Their serum concentrations of total, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, triglycerides, lipoprotein-(a) (Lp-(a)), total testosterone, estradiol and sex hormone-binding globulin (SHBG) were analyzed at baseline and after 24 weeks of each treatment. RESULTS: Serum levels of total testosterone increased markedly from a baseline mean of 0.8-4.9 nmol/l during testosterone addition. The levels of free testosterone significantly increased during the combined treatment and fell when given estrogen alone. Total and LDL-cholesterol levels were significantly reduced by both treatments as also were those of Lp-(a) although the difference was not significant. We found a 13% reduction in HDL-cholesterol levels when testosterone was added, but no change with estrogen alone. Triglyceride levels were increased by estrogen treatment, but not affected by the combination of estrogen plus testosterone. CONCLUSIONS: These findings suggest that 40 mg of TU can be given in addition to estrogen replacement with only little side-effects on the pattern of circulating lipids. Although supraphysiological concentrations of testosterone were induced a significant reduction in total and LDL-cholesterol levels occurred.

Cross-Over Studies↗

Androgen administration in middle-aged and ageing men: effects of oral testosterone undecanoate on dihydrotestosterone, oestradiol and prostate volume.

The gradual reduction of plasma testosterone in middle-aged and older men from mid-life onwards coincides paradoxically with the time when there is progressive growth of the prostate, a highly androgen-dependent organ. The growing interest in androgen therapy for older men makes it essential to understand the effects of exogenous testosterone on the non-diseased prostate, yet few studies are available. The present study examined prostate volume, prostate-specific antigen (PSA) and lower urinary tract symptom (IPSS) score in 207 men, aged 40-83 years, presenting with clinical features of age-related androgen deficiency [sexual and/or urinary dysfunction, elevated lutenizing hormone (LH)] who were treated for 6 months with oral testosterone undecanoate (TU). Men were divided into two groups, group 1 (n=92, plasma testosterone levels > 13 nmol/L) were treated with 80 mg daily; group 2 (n=115, plasma testosterone levels < 13 nmol/L) were treated with given 120 mg daily. Before treatment and after 1, 3 and 6 months of treatment, prostate volume was measured by ultrasound and hormones [testosterone, dihydrotestosterone, oestradiol, LH, follicle-stimulating hormone (FSH)] and PSA were measured. Within 1 month of treatment, the elevated blood LH levels were markedly decreased in all men in group 1, as well as most men in group 2. Group 2 was subdivided into men whose LH levels were suppressed (n=95, group 2a) and those whose LH levels did not suppress (n=20, group 2b). Men in group 1 and 2a had marked decreases in prostate volume, PSA and lower urinary tract symptom (IPSS) scores whereas no significant changes were observed in group 2b. Groups 1 and 2a also had more striking suppression of LH, FSH, dihydrotestosterone and oestradiol whereas group 2b had no significant increases in blood testosterone concentrations. These findings suggest that exogenous testosterone in middle-aged and older men with some clinical features of age-related androgen deficiency can retard or reverse prostate growth and that elevated plasma LH may be a useful index of severity of age-related androgen deficiency.

Adult↗

The biological activity of 7 alpha-methyl-19-nortestosterone is not amplified in male reproductive tract as is that of testosterone.

Based on the premise that testosterone, but not 7 alpha-methyl-androgens, is reduced at the 5 alpha-position in the prostate and seminal vesicles, the differential bioactivities of these androgens were investigated in castrated rats. The ability of 7 alpha-methyl-19-nortestosterone acetate (MENT) to increase the weights of ventral prostate and seminal vesicles of castrated rats was four times higher than that of testosterone, while its effect on the weights of bulbocavernosus plus levator ani muscles (muscle), was 10 times that of testosterone. MENT was also approximately 12 times more potent than testosterone in the suppression of serum gonadotropin levels. A dose of testosterone that maintains serum gonadotropin levels and muscle mass also maintains prostate and seminal vesicle weights in castrated rats. By contrast, a dose of MENT that maintains muscle and gonadotropins does not maintain prostate and seminal vesicles. The action of other 7 alpha-methylated androgens were similar to that of MENT. The importance of 5 alpha reductase in the differential action of testosterone and MENT on prostate was confirmed by using a 5 alpha-reductase inhibitor. The activity of testosterone was significantly suppressed in the ventral prostate and seminal vesicles but not on muscle by the 5 alpha-reductase inhibitor (N,N-diethyl-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta-carboxamide). The enzyme inhibitor, however, had no influence on the activity of MENT on either tissue. In contrast, cyproterone acetate, an antiandrogen that competitively binds to the androgen receptors, inhibited the action of MENT and of testosterone on the prostate as well as on the muscle. In conclusion, these observations show that 7 alpha-methylated androgens can maintain muscle mass and normal gonadotropin levels in androgen deficient rats without hyperstimulating the prostate. These findings suggest that 7 alpha-methylated androgens may offer some health benefits to men who require androgen treatment.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Combined estrogen and testosterone use and risk of breast cancer in postmenopausal women.

BACKGROUND: The role of androgens in breast cancer etiology has been unclear. Epidemiologic studies suggest that endogenous testosterone levels are positively associated with breast cancer risk in postmenopausal women. Given the increasing trend in the use of hormone therapies containing androgens, we evaluated the relation between the use of estrogen and testosterone therapies and breast cancer. METHODS: We conducted a prospective cohort study in the Nurses' Health Study from 1978 to 2002 to assess the risk of breast cancer associated with different types of postmenopausal hormone (PMH) formulations containing testosterone. During 24 years of follow-up (1 359 323 person-years), 4610 incident cases of invasive breast cancer were identified among postmenopausal women. Information on menopausal status, PMH use, and breast cancer diagnosis was updated every 2 years through questionnaires. RESULTS: Among women with a natural menopause, the risk of breast cancer was nearly 2.5-fold greater among current users of estrogen plus testosterone therapies (multivariate relative risk, 2.48; 95% confidence interval, 1.53-4.04) than among never users of PMHs. This analysis showed that risk of breast cancer associated with current use of estrogen and testosterone therapy was significantly greater compared with estrogen-only therapy (P for heterogeneity, .007) and marginally greater than estrogen and progesterone therapy (P for heterogeneity, .11). Women receiving PMHs with testosterone had a 17.2% (95% confidence interval, 6.7%-28.7%) increased risk of breast cancer per year of use. CONCLUSION: Consistent with the elevation in risk for endogenous testosterone levels, women using estrogen and testosterone therapies have a significantly increased risk of invasive breast cancer.

Adult↗

Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men.

CONTEXT: There is a compelling need for therapies that prevent, defer the onset, slow the progression, or improve the symptoms of Alzheimer disease (AD). OBJECTIVE: To evaluate the effects of testosterone therapy on cognition, neuropsychiatric symptoms, and quality of life in male patients with mild AD and healthy elderly men. DESIGN: Twenty-four-week, randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Memory disorders clinics as well as general neurology and medicine clinics from University of California medical centers at Los Angeles, San Francisco, and Irvine. PATIENTS OR OTHER PARTICIPANTS: Sixteen male patients with AD and 22 healthy male control subjects. Healthy elderly control men were recruited from the community through advertisements as well as through the university-based clinics. INTERVENTION: Testosterone and placebo, in the form of hydroalcoholic gel (75 mg), were applied daily to the skin of the participants. MAIN OUTCOME MEASURES: Instruments assessing cognitive functioning (Alzheimer's Disease Assessment Scale-Cognitive Subscale, California Verbal Learning Test, Block Design Subtest, Judgment of Line Orientation, Developmental Test of Visual-Motor Integration), neuropsychiatric symptoms (Neuropsychiatric Inventory), global functioning (Clinician's Interview-Based Impression of Change), and quality of life (Quality of Life-Alzheimer Disease Scale). RESULTS: For the patients with AD, the testosterone-treated group had significantly greater improvements in the scores on the caregiver version of the quality-of-life scale (P = .01). No significant treatment group differences were detected in the cognitive scores at end of study, although numerically greater improvement or less decline on measures of visuospatial functions was demonstrated with testosterone treatment compared with placebo. In the healthy control group, a nonsignificant trend toward greater improvement in self-rated quality of life was observed in the testosterone-treated group (P = .09) compared with placebo treatment. No difference between the treatment groups was detected in the remaining outcome measures. Testosterone treatment was well tolerated with few adverse effects relative to placebo. CONCLUSIONS: Results suggest that testosterone replacement therapy improved overall quality of life in patients with AD. Testosterone had minimal effects on cognition.

Affect↗

Diagnostic value of testosterone therapy in boys with delayed puberty.

A brief course of testosterone injections is known to be an effective treatment for boys with constitutional delayed puberty. In this study, data from seven boys at least 14 years old who received testosterone enanthate (100 mg intramuscularly monthly for four months) were analyzed to see if linear and testicular growth responses could be useful diagnostically in excluding growth hormone deficiency (GHD) and isolated gonadotropin deficiency, two conditions that are often difficult to distinguish from constitutional delayed puberty. During four months of testosterone therapy, growth rate increased from 4.0 +/- 1.0 cm/y to 10.7 +/- 2.3 cm/y, and was greater than 8 cm/y in all patients. Since testosterone-induced stimulation of linear growth is largely GH-mediated, the large increase in growth rate in all boys is considered indicative of GH sufficiency. Testis length, which did not increase during testosterone therapy, increased by 0.6 to 0.8 cm in every patient (from 2.7 +/- 0.3 cm to 3.4 +/- 0.4 cm) over the following four months, indicating normal gonadotropin secretion and normal pubertal progression; in contrast, the increase in serum testosterone concentrations after discontinuation of testosterone treatment was more variable. It is concluded that the growth response to a four-month course of testosterone is helpful in excluding GHD in boys with delayed puberty, and an additional four months of follow-up is sufficient to document the onset of puberty, thereby eliminating the possibility of isolated gonadotropin deficiency.

Adolescent↗

Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: a randomized controlled trial.

CONTEXT: Androstenedione, a precursor to testosterone, is marketed to increase blood testosterone concentrations as a natural alternative to anabolic steroid use. However, whether androstenedione actually increases blood testosterone levels or produces anabolic androgenic effects is not known. OBJECTIVES: To determine if short- and long-term oral androstenedione supplementation in men increases serum testosterone levels and skeletal muscle fiber size and strength and to examine its effect on blood lipids and markers of liver function. DESIGN AND SETTING: Eight-week randomized controlled trial conducted between February and June 1998. PARTICIPANTS: Thirty healthy, normotestosterogenic men (aged 19-29 years) not taking any nutritional supplements or androgenic-anabolic steroids or engaged in resistance training. INTERVENTIONS: Twenty subjects performed 8 weeks of whole-body resistance training. During weeks 1, 2, 4, 5, 7, and 8, the men were randomized to either androstenedione, 300 mg/d (n = 10), or placebo (n = 10). The effect of a single 100-mg androstenedione dose on serum testosterone and estrogen concentrations was determined in 10 men. MAIN OUTCOME MEASURES: Changes in serum testosterone and estrogen concentrations, muscle strength, muscle fiber cross-sectional area, body composition, blood lipids, and liver transaminase activities based on assessments before and after short- and long-term androstenedione administration. RESULTS: Serum free and total testosterone concentrations were not affected by short- or long-term androstenedione administration. Serum estradiol concentration (mean [SEM]) was higher (P<.05) in the androstenedione group after 2 (310 [20] pmol/L), 5 (300 [30] pmol/L), and 8 (280 [20] pmol/L) weeks compared with presupplementation values (220 [20] pmol/L). The serum estrone concentration was significantly higher (P<.05) after 2 (153 [12] pmol/L) and 5 (142 [15] pmol/L) weeks of androstenedione supplementation compared with baseline (106 [11] pmol/L). Knee extension strength increased significantly (P<.05) and similarly in the placebo (770 [55] N vs 1095 [52] N) and androstenedione (717 [46] N vs 1024 [57] N) groups. The increase of the mean cross-sectional area of type 2 muscle fibers was also similar in androstenedione (4703 [471] vs 5307 [604] mm2; P<.05) and placebo (5271 [485] vs 5728 [451] mm2; P<.05) groups. The significant (P<.05) increases in lean body mass and decreases in fat mass were also not different in the androstenedione and placebo groups. In the androstenedione group, the serum high-density lipoprotein cholesterol concentration was reduced after 2 weeks (1.09 [0.08] mmol/L [42 (3) mg/dL] vs 0.96 [0.08] mmol/L [37 (3) mg/dL]; P<.05) and remained low after 5 and 8 weeks of training and supplementation. CONCLUSIONS: Androstenedione supplementation does not increase serum testosterone concentrations or enhance skeletal muscle adaptations to resistance training in normotestosterogenic young men and may result in adverse health consequences.

Administration, Oral↗

Characterization of exogenous testosterone in livestock by gas chromatography/combustion/isotope ratio mass spectrometry: influence of feeding and age.

The detection of exogenous testosterone in bovine urine was investigated by using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). The carbon isotopic ratio measurement of epitestosterone, etiocholanolone (testosterone metabolite) and DHEA (testosterone precursor) in female bovine urines after testosterone enanthate administration was carried out. An important modification in the 13C/12C ratio of testosterone metabolites was observed, such that significant differences between precursor and metabolites of testosterone occurred until three weeks after intramuscular administration of testosterone enanthate. The factors influencing the 13C/12C of endogenous steroids were studied especially through cattle feeding and age. The DHEA mean delta13C value was found to vary between -25 and -26/1000 when hay and concentrate diet were used for fattening. On the other hand the delta13C value observed when maize silage was used increased to -20/1000. Testosterone metabolites showed the same delta13C increase as their precursor. Moreover, we observed a clear relationship between age and efficiency of misuse determination. Indeed, because of the lower concentration of natural hormones in young animals, the contribution of exogenous molecules increases significantly compared with older subjects. Consequently, demonstration of administration is easier to achieve in calves than in mature animals.

Aging↗

Roles of photoperiod and testosterone in seasonal plasticity of the avian song control system.

The song control nuclei of songbirds undergo pronounced seasonal changes in size and neuronal attributes. The mechanisms by which seasonal changes in environmental variables such as photoperiod mediate seasonal changes in these brain regions are not known. Manipulations of photoperiod and/or testosterone in captive songbirds induce seasonal changes in the size of song nuclei comparable to those observed in wild songbirds. It is unclear, however, whether the effects of photoperiod on the song nuclei are mediated by testosterone or by steroid-independent mechanisms. We independently manipulated photoperiod and testosterone in castrated male Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) to determine the contributions of steroid-dependent and -independent actions of photoperiod to seasonal changes in the size and neuronal attributes of song nuclei. Testosterone implants increased the size of several song nuclei, regardless of photoperiod. Photoperiod exerted small but significant steroid-independent effects on the volume of the higher vocal center and the size of neurons in the robust nucleus of the archistriatum. Photoperiod also modulated the effect of testosterone on the size of area X; testosterone treatment had a more pronounced effect on the size of area X on short days than on long days. These results suggest that although testosterone is the primary factor mediating seasonal changes in neural attributes of the song nuclei, photoperiod may act via mechanisms that are independent of steroid levels to supplement or modulate the actions of testosterone.

Animals↗

Comparison of components of the testis interstitium with testosterone secretion in hamster, rat, and guinea pig testes perfused in vitro.

Components of the testis and cytoplasmic organelles in Leydig cells were quantified with morphometric techniques in hamster, rat, and guinea pig. Testosterone secretory capacity per gram of testis and per Leydig cell in response to luteinizing hormone (LH) (100 ng/ml) stimulation was determined in these three species from testes perfused in vitro. Numerous correlations were measured among structures, and between structures and testosterone secretion, to provide structural evidence of intratesticular control of Leydig cell function. Testosterone secretion per gm testis and per Leydig cell was significantly different in the three species: highest in the guinea pig, intermediate in the rat, and lowest in the hamster. The volume of seminiferous tubules per gm testis was negatively correlated, and the volumes of interstitium, Leydig cells, and lymphatic space per gm testis were positively correlated with testosterone secretion. No correlations were observed between volumes of blood vessels, elongated spindleshaped cells, or macrophages per gm testes and testosterone secretion. The average volume of a Leydig cell and the volume and surface area of smooth endoplasmic reticulum (SER) and peroxisomes per Leydig cell were positively correlated, and the volume of lysosomes and surface area of inner mitochondrial membrane per Leydig cell were negatively correlated with testosterone secretion. No correlations were observed between volume and surface area of rough endoplasmic reticulum (RER), Golgi apparatus, and lipid, and volume of ribosomes, cytoplasmic matrix, and the nucleus with testosterone secretion per Leydig cell. These results suggest that Leydig cell size is more important than number of Leydig cells in explaining the difference in testosterone-secreting capacity among the three species, and that this increase in average volume of a Leydig cell is associated specifically with increased volume and surface area of SER and peroxisomes. An important unresolved question is what is the role of peroxisomes in Leydig cell steroidogenesis.

Analysis of Variance↗

Predictors of South African male testosterone levels: the THUSA study.

The process of urbanization occurring in many developing countries may have consequences for reproductive endocrine function. Here, we test predictions concerning variation in South African male testosterone levels among subgroups across an urbanization gradient representing differences in both geography and socioeconomic status. Subjects included 364 males aged between 20 and 82 comprising a cross-sectional study conducted between 1996 and 1998. Testosterone levels were measured from serum samples obtained between 08:00 and 11:00. In ANCOVA analysis, male testosterone levels differed significantly along this rural-to-urban gradient, with members of the most urban group having higher testosterone levels than groups of farmers and inhabitants of informal housing areas adjacent to towns. Testosterone levels declined with age and were negatively related to body mass index (BMI). Testosterone levels did not differ according to HIV status. Further exploratory ANCOVA analyses revealed that physical activity levels, depression, affect, and hostility were not significantly associated with variation in testosterone levels. These data help document causes of variation in male testosterone levels in a context of urbanization and may have implications for clinical outcomes such as the development of a male hormonal contraceptive or prostate cancer.

Adult↗

Testosterone suppresses anti-DNA antibody production in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.

OBJECTIVE: To study the in vitro effect of testosterone on anti-DNA antibody production in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE) in order to elucidate its regulatory role in SLE. METHODS: PBMC from SLE patients were cultured with testosterone. IgG anti-double-stranded DNA (anti-dsDNA) antibody, total IgG, and cytokine activity in the supernatants were measured by enzyme-linked immunosorbent assay. RESULTS: Testosterone suppressed both IgG anti-dsDNA antibody and total IgG production in PBMC from SLE patients. Antibody production in B cells was also suppressed by testosterone, although the magnitude of its effect on B cells was lower than that on PBMC. Interleukin-6 (IL-6) partially restored the testosterone-induced decrease in antibody levels in PBMC. Testosterone reduced IL-6 production in monocytes. CONCLUSION: These results suggest that testosterone may directly suppress anti-DNA antibody production in PBMC from SLE patients by inhibiting B cell hyperactivity and, indirectly, by down-regulating IL-6 production in monocytes. These results support the therapeutic effects of testosterone on SLE.

Adult↗

Evaluation of the pharmacokinetic profiles of the new testosterone topical gel formulation, Testim, compared to AndroGel.

A two-period, randomized, complete crossover study was performed to evaluate the pharmacokinetic profiles of Testim (AA2500), a new 1% testosterone topical gel formulation, compared to AndroGel, an already available 1% testosterone topical gel. Twenty-nine hypogonadal subjects received a single dose (50 mg testosterone) of each formulation seven days apart. C(max) estimates for total testosterone, dihydrotestosterone and free testosterone were greater (30, 19 and 38%, respectively) following the application of Testim compared to AndroGel. Similarly, AUC(0-24) estimates for total testosterone, dihydrotestosterone, and free testosterone were greater (30, 11 and 47%, respectively) following the application of Testim compared to AndroGel. Confidence intervals for C(max) and AUC(0-24) were not wholly contained within the bioequivalence limits for testosterone, therefore Testim trade mark and AndroGel are not bioequivalent with Testim providing higher serum levels and greater bioavailability than AndroGel.

Administration, Topical↗

Pharmacokinetic studies of testosterone propionate using gas chromatography/mass spectrometry/selected ion monitoring.

A sensitive and accurate method for the quantitative estimation of testosterone propionate in human plasma was developed using gas chromatography/mass spectrometry/selected ion monitoring. The method employing stable isotopically labelled testosterone propionate as tracer was employed to follow the time course of plasma testosterone propionate and its active metabolite testosterone in normal men. Intramuscularly administered (19,19,19-2H3)testosterone propionate was readily transferred from the injection site to systemic circulation. Plasma (19,19,19-2H3)testosterone levels were maintained above the physiological testosterone level for 48 h, while plasma levels of endogenous testosterone changed little.

Adult↗