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PubMed1994

The grasp reflex from the right and left hand in human neonates indicates that the development of both cerebral hemispheres in males, but only the right hemisphere in females, is favoured by testosterone.

The grasp reflex was studied in relation to serum free testosterone levels in human neonates. In the total and -FS (no familial sinistrality) males, the grasp reflex (especially that from the right hand) significantly increased as testosterone increased. In the total and -FS females, there was a significant positive linear correlation between testosterone and the grasp-reflex strength from the left hand, but not from the right hand. In +FS males, there was a significant negative correlation between the grasp-reflex strength from the left hand and testosterone, but not from the right hand; there were no significant correlations in the +FS females. The right minus left (R - L) grasp-reflex strength linearly increased with testosterone in females with normal testosterone levels, but linearly decreased in females with high testosterone levels. The log R - L grasp reflex increased with testosterone in males. It was concluded that testosterone may be beneficial for the development of the left brain in -FS males and the left brain in -FS females, but may have detrimental effects on the right brain in +FS males. The growth-promoting asymmetric effects of testosterone on the brain may depend upon genetic organization of the brain.

Brain↗

PubMed1996

Maternal testosterone in the avian egg enhances postnatal growth.

The eggs of the canary (Serinus canaria) contain variable doses of maternal testosterone. The reported experiments investigated whether testosterone influences nestling growth and how this interacts with differences of the growth of nest mates that are caused by asynchronous hatching. Injections of testosterone into the yolk of unincubated eggs enhanced the growth after hatching compared to nestlings that had hatched simultaneously from control eggs. These differences were established within 22 hr of hatching. Exogenous testosterone promoted growth in both sexes and there was no sexual difference in the growth of control birds. Testoster-one-treated chicks also begged more often for food. Previous studies have shown that the content of maternal testosterone increases in each subsequently laid egg in a clutch. Consistent with the results obtained by testosterone injections nestlings that hatched from eggs with higher concentrations of maternal testosterone grew faster compared to chicks that hatched synchronously from eggs with lower testosterone concentrations. However, more testosterone did not compensate for reduced growth that was caused by later hatching due to asynchronous incubation of clutches. This direct effect of maternal testosterone on growth in combination with a flexible onset of incubation allows to selectively enhance the growth and fitness of individual offspring of a brood.

Age Factors↗

PubMed1995

Testosterone stimulates the biosynthesis of m-aconitase and citrate oxidation in prostate epithelial cells.

Mitochondria (m-)aconitase is a rate-limiting regulatory enzyme in prostate epithelial cells which minimizes citrate oxidation by these cells. This unique metabolite characteristic is responsible for the ability of the prostate to accumulate and secrete extraordinarily high levels of citrate. Testosterone is a major regulator of prostate growth and function, and stimulates citrate oxidation. Therefore, an important action of testosterone might be its stimulation of m-aconitase in prostate epithelial cells. Studies were conducted with rat ventral prostate (VP) epithelial cells to establish the effect of testosterone on the level of m-aconitase and corresponding citrate oxidation. Physiological concentrations (10(-7)-10(-10) M) of testosterone in vitro markedly increased the level of m-aconitase in freshly prepared isolated prostate epithelial cells. This increase was apparent within 3 h of exposure to the hormone. The stimulatory effect of testosterone on m-aconitase was abolished by actinomycin D and by cycloheximide. Both the level of m-aconitase enzyme and the level of m-aconitase activity were similarly increased by testosterone treatment. Correspondingly, testosterone increased the rate of mitochondrial citrate oxidation while having no effect on the rate of isocitrate oxidation, thereby demonstrating that the action of testosterone is specifically targeted at the m-aconitase reaction. In vivo studies revealed that castration markedly decreased and testosterone administration increased the m-aconitase level of prostate epithelial cells. In contrast, neither liver nor kidney m-aconitase level was altered by castration. These studies demonstrate that testosterone regulates the biosynthesis of m-aconitase in prostate epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aconitate Hydratase↗

PubMed1991

Effect of cortisol on testosterone production by immature pig Leydig cells.

The direct effects of hydrocortisone (HS) and adrenocorticotropin (ACTH) on testicular testosterone production were studied in purified immature pig Leydig cells in vitro. Leydig cells were obtained from 3- to 4-week-old piglet testes by enzymatical dispersion followed by discontinuous Percoll gradient centrifugation. Leydig cells were treated with HS and ACTH in the absence or presence of luteinizing hormone (LH) after 12 h of incubation. Media were collected 48 h later for testosterone and cyclic adenosine 3',5'-monophosphate (cAMP) measurement. Treatment of Leydig cells with increasing concentrations (0.001-10.0 micrograms/ml) of HS for 48 h resulted in a dose-dependent increase in basal and LH-stimulated testosterone production. Increasing duration (6-72 h) of treatment with HS (100 ng/ml) led to a time-dependent increase in basal and LH-stimulated testosterone production, achieving statistical significance by 48 and 24 h, respectively. HS increased LH-stimulated cAMP production. HS also increased testosterone production induced by (Bu)2 cAMP. Forskolin stimulated testosterone production to an extent comparable to that attained with LH, and HS augmented forskolin-stimulated testosterone production. HS enhanced the conversion of exogenous 17 alpha-hydroxyprogesterone to testosterone, but did not affect the conversion of pregnenolone and progesterone to testosterone, suggesting a specific stimulation of 17,20-desmolase. Porcine ACTH had no influence on basal and LH-stimulated testosterone production. These results suggest that HS directly stimulates immature pig Leydig cell steroidogenesis, at least in part via an enhancement of the generation of cAMP, leading to an increase in the activity of 17,20-desmolase.

17-alpha-Hydroxyprogesterone↗

PubMed2004

Postmenopausal testosterone therapy and breast cancer risk.

BACKGROUND: Testosterone therapy is being increasingly used in the management of postmenopausal women. However, as clinical trials have demonstrated a significantly increased risk of breast cancer with oral combined estrogen-progestin therapy, there is a need to ascertain the risk of including testosterone in such regimens. OBJECTIVE: Evaluation of experimental and epidemiological studies pertaining to the role of testosterone in breast cancer. DESIGN: Literature review. SETTING: The Jean Hailes Foundation, Research Unit. MAIN OUTCOME MEASURES: Mammary epithelial proliferation, apoptosis and breast cancer. RESULTS: In experimental studies, testosterone action is anti-proliferative and pro-apoptotic, and mediated via the AR, despite the potential for testosterone to be aromatized to estrogen. Animal studies suggest that testosterone may serve as a natural, endogenous protector of the breast and limit mitogenic and cancer promoting effects of estrogen on mammary epithelium. In premenopausal women, elevated testosterone is not associated with greater breast cancer risk. The risk of breast cancer is also not increased in women with polycystic ovary syndrome who have chronic estrogen exposure and androgen excess. However, in postmenopausal women, who are oestrogen deplete and have increased adipose aromatase activity, higher testosterone has been associated with greater breast cancer risk. CONCLUSION: Available data indicate the inclusion of testosterone in estrogen-progestin regimens has the potential to ameliorate the stimulating effects of hormones on the breast. However, testosterone therapy alone cannot be recommended for estrogen deplete women because of the potential risk of enhanced aromatisation to estrogen in this setting.

Animals↗

PubMed2004

Development of a highly sensitive and specific new testosterone time-resolved fluoroimmunoassay in human serum.

A new time-resolved fluoroimmunoassay (TR-FIA) of testosterone in serum is described, using a biotinylated testosterone tracer, with a long spacer arm between biotin and testosterone, coupled to the C3 of the testosterone: a biotinylaminodecane carboxymethyloxime testosterone. This tracer affords a great sensitivity of the standard curve, because a amount of 0.3 pg of testosterone can be significantly measured on the testosterone standard curve. The "functional" sensitivity is at least equal to 21 pg/ml of serum. The specificity of the assay is insured by a celite chromatographic step on new minicolumns before immunoassay. The variation coefficient of inter-series reproducibility measured on low and normal testosterone levels in untreated and testosterone treated hypogonadal men were between 2.17 and 5.07%. The accuracy test, (overload and dilution tests) gave satisfying results. Moreover, in a comparison with GCMS, it appeared that the correlation coefficient was 0.992 and no significant difference could be exhibited between the two methods. Consequently, this specific, sensitive reproducible and easy to use method is well suited to the measurement of testosterone in clinical and pharmacological conditions.

Biotin↗

PubMed2004

Consequences of elevating plasma testosterone in females of a socially monogamous songbird: evidence of constraints on male evolution?

To explore whether selection for testosterone-mediated traits in males might be constrained by costs of higher testosterone to females, we examined the effects of experimental elevation of plasma testosterone on physiological, reproductive, and behavioral parameters in a female songbird, the dark-eyed junco (Junco hyemalis). We used subcutaneous implants to elevate testosterone (T) in captive and free-living female juncos. In captive birds, we measured the effects of high T on body mass, feather molt, and brood patch formation. In the field, we monitored its effects on the timing of egg laying, clutch size, egg size, egg steroid levels, incubation, and nest-defense behavior. Females implanted with testosterone (T-females) had significantly higher circulating levels of testosterone than did control females (C-females). Captive T-females had lower body mass, were less likely to develop brood patches, and delayed feather molt relative to C-females. Among free-living females, the interval between nest completion and appearance of the first egg was longer for T-females than for C-females and egg yolk concentrations of testosterone were higher, but there were no significant differences in estradiol levels, clutch size, or egg size. Incubation and nest defense behavior were also similar between T- and C-females. Our results suggest that selection on males for higher testosterone might initially lead to a correlated response in females producing changes in body mass and feather molt, both of which could be detrimental. Other possible female responses would be delayed onset of reproduction, which might reduce reproductive success, and higher yolk testosterone, which might have either positive or negative effects on offspring development. We found no reason to expect reduced parental behavior by females as a negative fitness consequence of selection for higher testosterone in males.

Animals↗

PubMed2004

European starling chicks benefit from high yolk testosterone levels during a drought year.

Avian egg yolk contains androgenic hormones, such as testosterone, of maternal origin. Experimental elevation of yolk testosterone levels enhances growth of canary chicks. Success in sibling competition, due to increased begging, is presumed to underlie this growth enhancement, because canary hatchlings from testosterone-treated eggs beg longer in response to vibrational stimuli than controls. Furthermore, experimental elevation of both yolk androstenedione and testosterone increased chick growth and begging in black-headed gulls. We measured daily growth of European starling (Sturnus vulgaris) chicks hatching from testosterone-treated or vehicle-treated (control) eggs until 14 days of age, and measured begging behavior at hatching and at 5 days of age. A temporary drought caused relatively high levels of early brood reduction for this population; 2- and 3-day-old chicks were most likely to starve. We found that chicks from testosterone-treated eggs were less likely to starve than control chicks, and were heavier on the days when most brood reduction occurred. However, chicks from testosterone-treated eggs begged less than control chicks on the day of hatching, and begged similarly at 5 days of age. Thus, while yolk testosterone did increase growth during periods of (presumably) high competition, increased begging does not appear to mediate this effect. Instead, testosterone may induce more efficient energy use, for example, by decreasing ineffective begging. While our results indicate that elevated yolk testosterone enhances survival, and thus offspring and parental fitness, further evidence regarding the fitness consequences of yolk androgens are vital to understanding their role in avian life history.

Adaptation, Physiological↗

PubMed2005

Testosterone and autumn territorial behavior in male red grouse Lagopus lagopus scoticus.

In many bird species, males exhibit territorial aggression outside the breeding season, when testosterone concentrations are low and may not regulate territorial behaviors. The hormonal regulation of aggression at this time of year has only been studied in passerine birds. Here, we investigated the role of testosterone in the regulation of aggression in a non-passerine bird, the red grouse Lagopus lagopus scoticus. Male red grouse are aggressive in early spring when breeding starts, in autumn when they establish territories, and sporadically through much of the winter. We first describe seasonal variations in plasma testosterone concentrations and in the size of males' sexual ornaments, their red combs, which relates to aggressiveness. Testosterone concentrations and comb size were correlated. Both increased in autumn to a peak in October, and then increased again in spring, to a greater peak in early April. Secondly, we experimentally investigated the effects of testosterone, and of an anti-androgen (flutamide) used in combination with an aromatase inhibitor (ATD), on autumn territorial behavior. Males were treated with either empty implants, as controls (C-males), testosterone implants (T-males), or with flutamide and ATD implants (FA-males). One month after implanting, both T- and FA-males had higher concentrations of testosterone than C-males. Comb size, aggressive call rate, and response to playbacks of territorial call all significantly increased in T-males. However, the increase in testosterone in FA-males did not increase comb size or aggressive behavior. In the following spring, after the content of implants was used, FA-males had significantly lower testosterone than C-males, and had a reduced seasonal increase in comb size. The results suggest that testosterone plays a significant role in regulating red grouse aggressive behavior in autumn. However, the observation that flutamide and ATD treatment did not reduce territorial behavior, suggests that estradiol may also be involved in the regulation of non-breeding aggression.

Androgen Antagonists↗

PubMed2006

Sexually stimulated testosterone release in male mice (Mus musculus): roles of genotype and sexual arousal.

In virtually every mammalian species examined, some males exhibit reflexive testosterone release upon encountering a novel female (or female-related stimulus). At the same time, not every individual male (or every published study) provides evidence for reflexive testosterone release. Four experiments using house mice (Mus musculus) examined the hypothesis that both the male's genotype and his degree of sexual arousal (as indexed by ultrasonic mating calls) are related to such variability. In Experiment 1, CF-1 males exhibited reflexive testosterone elevations 30 min after encountering female urine. CK males, on the other hand, did not exhibit testosterone elevations 20, 30, 50, 60, or 80 min after encountering female urine (Experiments 1 and 2) suggesting this strain incapable of reflexive release. In Experiment 3, we measured both mating calls and reflexive testosterone release in response to female urine in CF-1 and CK males. Most males of both strains called vigorously to female urine but not to water. But, only CF-1 males exhibited significant testosterone elevations to female urine. In Experiment 4, DBA/2J males called vigorously to females followed by testosterone elevations 30 min later. The first 3 experiments support the hypothesis that male genotype is an important variable underlying mammalian reflexive testosterone release. Statistically significant correlations between mating calls in the first minute after stimulus exposure and testosterone elevations 30 min later (Experiments 3 and 4) support the hypothesis that, in capable males, reflexive testosterone release is related to the male's initial sexual arousal.

Analysis of Variance↗

PubMed2001

Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age.

PURPOSE: Because the effects of androgen replacement on lipoprotein levels are uncertain, we sought to determine the effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in elderly men. SUBJECTS AND METHODS: One hundred and eight healthy men more than 65 years of age who had serum testosterone concentrations >1 SD below the mean for young men were randomly assigned to receive either testosterone (54 men; 6 mg/day) or placebo (54 men) transdermally in a double-blind fashion for 36 months. Serum concentrations of lipids and apolipoproteins were measured, and cardiovascular events recorded. RESULTS: Serum total cholesterol concentrations decreased in both the testosterone-treated men and placebo-treated men, but the 3-year mean (+/- SD) decreases in the two groups (testosterone treated, -17 +/- 29 mg/dL; placebo treated, -12 +/- 38 mg/dL) were not significantly different from each other (P = 0.4). Similarly, serum low-density lipoprotein (LDL) cholesterol levels decreased in both treatment groups, but the decreases in the two groups (testosterone treated, -16 +/- 24 mg/dL; placebo treated, -16 +/- 33 mg/dL) were similar (P = 1.0). Levels of high-density lipoprotein (HDL) cholesterol, triglycerides, and apolipoproteins A-I and B did not change. Lipoprotein(a) levels increased in both groups by similar amounts (testosterone treated, 3 +/- 9 mg/dL; placebo treated, 4 +/- 6 mg/dL; P = 1.0). The number of cardiovascular events was small and did not differ significantly between the testosterone-treated men (9 events) and the placebo-treated men (5 events) during the 3-year study (relative risk = 1.8; 95% confidence interval: 0.7 to 5.0). CONCLUSIONS: As compared with placebo, transdermal testosterone treatment of healthy elderly men for 3 years did not affect any of the lipid or apolipoprotein parameters that we measured. The effect of testosterone treatment on cardiovascular events was unclear, because the number of events was small.

Administration, Cutaneous↗

PubMed2002

Sex differences in models of temporal lobe epilepsy: role of testosterone.

Kainic acid and pilocarpine were used to assess sex differences in temporal lobe seizures. Adult Sprague-Dawley rats were injected with kainic acid (10-12 mg/kg) or with pilocarpine (380 mg/kg) and behavior was recorded for the next 3 h. Trunk blood was collected for hormonal measurements. Our data indicate that the male is more susceptible to the convulsant effects of agents that produce temporal lobe-like seizures. Males presented a higher amount of full limbic convulsions than females. To assess the role of plasma testosterone levels in kainate-induced seizures, a group of males was gonadectomized and half received testosterone replacement. The presence of testosterone, in intact and in gonadectomized males with testosterone replacement, increased the susceptibility to seizure. Seizures were either stronger (full limbic) or more frequent in animals with testosterone compared to animals devoid of testosterone. These results suggest that differences in plasma levels of testosterone may be partially responsible for the observed gender differences in seizure susceptibility. Our data reveal a reciprocal relationship between kainic acid-induced temporal lobe seizures and plasma testosterone. Testosterone enhances the occurrence and the severity of seizures. Conversely, kainic-acid-induced seizures decrease plasma testosterone. The higher plasma corticosterone levels found in these males suggest that kainic acid-induced seizures activate the hypothalamic-pituitary-adrenal axis which may induce alterations in plasma levels of male reproductive hormones.

Animals↗

PubMed2000

Desogestrel plus testosterone effectively suppresses spermatogenesis but also causes modest weight gain and high-density lipoprotein suppression.

OBJECTIVE: To test the hypothesis that oral desogestrel (DSG) plus testosterone would uniformly and rapidly suppress sperm concentrations in young men as effectively as levonorgestrel (LNG) plus testosterone and cause less high-density lipoprotein (HDL) suppression and weight gain. DESIGN: Single-blind, randomized trial. SETTING: VA Puget Sound and University of Washington, Seattle, Washington. PATIENT(S): Twenty-four healthy young men, aged 20-49. INTERVENTION(S): Subjects were randomized to three groups of men who were administered 6 months of therapy with oral DSG plus im testosterone enanthate: 150 microg of DSG plus 50 mg of testosterone (DSG 150-T 50), 150 microg of DSG plus 100 mg of testosterone (DSG 150-T 100) or 300 microg of DSG plus 100 mg of testosterone (DSG 300-T 100). We compared these three groups to two groups of historical controls of 100 mg of im testosterone alone or 150 microg of oral LNG plus 100 mg of im testosterone (LNG 125-T 100 group) enrolled in similar studies. MAIN OUTCOME MEASURE(S): Suppression of sperm counts to severe oligoazoospermia (sperm counts <1 x 10(6)/mL) and azoospermia, weight gain, and serum high-density cholesterol (HDL) suppression. RESULT(S): Azoospermia was achieved in all eight men receiving DSG 150-T 100 and seven of the eight men in the DSG 300-T 100 group. DSG 150 or 300 plus T 100 suppressed spermatogenesis as effectively as LNG 125-T 100 and more effectively than DSG 50-T 100 or testosterone alone. All groups tended to gain weight compared with their baseline, but the weight gain was greatest (and statistically significant) in the DSG 150-T 100, DSG 300-T 100, and LNG 125-T 100 groups. Serum HDL levels were modestly suppressed in all groups, and this effect was greatest in the DSG 300-T 100 and LNG 125-T 100 groups. CONCLUSION(S): The combination of DSG plus testosterone is a very effective regimen for suppression of spermatogenesis and has acceptably low side effects.

Acne Vulgaris↗

PubMed2003

Testosterone is correlated with courtship but not aggression in the tropical buff-banded rail, Gallirallus philippensis.

Past studies into the roles of testosterone in birds have focused on species that occur in temperate regions. In such species, plasma testosterone levels are high during the establishment of territories in the spring and are associated with increased aggression. In contrast to most temperate species, tropical birds frequently defend territories year-round, during which time territoriality often occurs in a nonsexual context. The few studies that have been carried out on tropical birds show lower levels of circulating testosterone than occur in their temperate counterparts. In some year-round territorial tropical species, testosterone and aggression are dissociated, while in other species testosterone still plays a role in regulating aggression. This study examined the relationship between aggression and plasma testosterone levels in a year-round territorial, subtropical population of the buff-banded rail with characteristics typical of tropical species. Peak testosterone levels were substantially lower than those found in temperate species. Males displayed a seasonal peak in plasma testosterone level when their partners were most likely to be fertile. At other times, testosterone levels were mostly undetectable, despite year-round territoriality. We found that T levels increased with courtship behavior but showed no relationship with aggression, supporting the hypothesis that dissociation between testosterone and territoriality may be widespread among tropical avian taxa.

Aggression↗

PubMed1997

Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men.

Cross-sectional studies have demonstrated a decline in testosterone and free and bioavailable testosterone with age. This occurs in a majority of older persons without an increase in luteinizing hormone (LH), suggesting that a component of the testosterone decrease is due to secondary hypogonadism. To determine whether these findings could be duplicated in a longitudinal study, we measured testosterone, LH, follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) levels in 77 men participating in the New Mexico Aging Process Study who had sera available in 1980 or 1981 and two or more serial samples in 1982, 1984, 1989, and/or 1994. Thirty-nine subjects had samples available from both 1980 and 1994. The age at entry into the study ranged from 61 to 87 years. Testosterone levels decreased over the 15 years of the study. In persons who were alive for the duration of the study, testosterone levels were significantly lower 5 years before termination of the study (P < .05). Testosterone levels did not differ at entry into the study among those who died and those who were alive at the end of the study period. Eight of 77 subjects (10%) had LH levels above the normal range at some time during the study. In contrast, 43% of subjects had elevated FSH levels. Both LH and FSH increased significantly with age. SHBG levels were measured in 1980 and 1994 and increased significantly with age (P < .0001). LH and FSH were highly correlated with one another, but neither correlated with testosterone. This study demonstrated a longitudinal decline in testosterone and an increase in LH and FSH in older men. The average rate of decrement in testosterone concentration was 110 ng/dL every decade.

Aged↗

PubMed2000

Urinary testosterone levels in the male blind mole rat (Spalax ehrenbergi) affect female preference.

This study investigated the sexual attraction of female blind mole rats to four groups of male mole rats: (a) intact males raised in captivity; (b) intact males trapped in the field; (c) captive males injected with testosterone; (d) captive castrated males. In the first part we measured blood testosterone, androstenedione, and dihydrotestosterone (DHT) levels, by radioimmunoassay; and urine testosterone levels, measured by GC-MS. The second part examined the relationship between urine testosterone levels in males and their attractiveness to females. Higher blood and urine testosterone levels were found in the field animals and in those injected with testosterone compared to captive intact or castrated animals: urine testosterone levels in the two other groups were not detectable. Blood androstenedione levels were also higher in the field animals and in those injected with testosterone compared to captive intact or castrated mole rats. Blood dihydrotestosterone levels were not detectable in all four experimental groups. Female mole rats chose to spend a longer period of time next to males with high blood and urine testosterone levels and high blood androstenedione levels than next to those with lower levels of these hormones. Because courtship and sexual behavior are influenced both by high levels of blood and urine testosterone and high levels of blood androstenedione, we suggest that the low levels of courtship and other sexual behavior in captive mole rats may be related to the lack of female attraction to these males, which display low levels of all three parameters.

Androstenedione↗

PubMed2002

Testosterone signaling in T cells and macrophages.

This review summarizes data about non-genomic actions of testosterone on murine malaria, T cells and macrophages produced by our group during the last 15 years. In C57BL/10 mice, testosterone induces a lethal outcome of blood stage infections with Plasmodium chabaudi which normally takes a self-healing course controlled by genes of the H-2 complex and the non-H-2 background. This suppressive effect of testosterone is mediated neither via the classic intracellular androgen receptor (AR) response nor, after conversion of testosterone to estradiol, via the estrogen receptor. Testosterone acts non-genomically, i.e. through surface receptors, on murine T cells and macrophages, which becomes evident as a rapid rise in the intracellular free Ca(2+) concentration ([Ca(2+)](i)). In T cells, this rise reflects predominantly influx of extracellular Ca(2+), while it is predominantly due to release of Ca(2+) from intracellular Ca(2+)-stores in macrophages. The testosterone-induced rise in [Ca(2+)](i) of both macrophages and T cells is not inhibited by the AR-blocker cyproterone, and it is also inducible by the plasma membrane impermeable ligand testosterone-BSA. The surface receptors initiate a transcription-independent signaling pathway of testosterone. Currently, we are trying to isolate testosterone surface receptors and to investigate a possible cross-talk of non-genomic testosterone signaling with other genotropic signaling pathways.

Animals↗

PubMed2000

New clinical applications of transdermal testosterone delivery in men and women.

This paper reviews recent progress in the development and clinical application of testosterone transdermal delivery systems designed for physiological replacement therapy in men and women. The biopharmaceutic goal of physiologic replacement therapy is to produce serum levels and circadian patterns of testosterone and its active metabolites that mimic the normal physiology of testosterone in the particular target population. For the treatment of adult hypogonadal men, the nightly 24 h application of the Androderm testosterone transdermal system (5 mg per day) achieves this goal - as demonstrated in a series of clinical pharmacokinetic studies. For the treatment of adolescent males, physiologic replacement can be approximated by modifying the dose and duration of Androderm application so as to mimic the patterns of nocturnal testosterone secretion observed during puberty. With the objective of providing physiological replacement for women with diminished testosterone production, an experimental testosterone matrix transdermal system (TMTDS) has been developed and is currently undergoing clinical evaluation. In parallel with the development of testosterone transdermal systems, physicians have been investigating a number of conditions, in both males and females, where testosterone production is diminished and replacement therapy may be beneficial. Three of these new clinical applications will be illustrated - the use of Androderm for the treatment of adolescent males with beta-thalassemia, the use of Androderm for the treatment of HIV+ men, and the use of the TMTDS for the treatment of HIV+ women. From the biopharmaceutic and clinical perspectives, the development of testosterone transdermal systems represents an important achievement in controlled drug delivery.

Administration, Cutaneous↗