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PubMed2001

Testosterone and nerve growth factor have distinct but interacting effects on structure and neurotransmitter expression of adult pelvic ganglion cells in vitro.

Circulating testosterone has potent effects on the structure and function of many pelvic ganglion cells in adult rats in vivo. However not all androgen-sensitive pelvic neurones possess androgen receptors and testosterone effects may therefore be indirect, by an action on the target organs. Here we have examined if testosterone influences neuronal structure in vitro in pelvic ganglion cells cultured from adult male rats. We have also used multiple label immunofluorescence to monitor the expression of transmitter-synthesising enzymes and peptides under various culture conditions. Testosterone was a more potent stimulant of noradrenergic soma growth in culture than nerve growth factor. Whereas nerve growth factor increased the number, branching and length of neurites, testosterone stimulated growth of a small number of very short processes, each of which bore numerous short protrusions. Testosterone also impeded the longer neurite growth induced by nerve growth factor. Many pelvic ganglion cells altered their expression of transmitters/neuropeptides under different culture conditions. In particular, under control conditions or during nerve growth factor treatment, vasoactive intestinal peptide was up-regulated in noradrenergic and cholinergic neurones; testosterone impeded this up-regulation in noradrenergic neurones. Choline acetyltransferase immunoreactivity could only be visualised when nerve growth factor was present in the cultures, and cholinergic neurones showed less neurite outgrowth than noradrenergic neurones under all culture conditions. Nerve growth factor did not stimulate levels of this enzyme as strongly if testosterone was present. This study has shown that testosterone has potent effects on the structure of many pelvic ganglion cells in vitro. It is possible that these effects are mediated indirectly, e.g. by stimulating glial-derived substances, however our results suggest that the effects are not mediated by nerve growth factor. The results also show that testosterone influences some of the actions of nerve growth factor, suggesting that there may be complex interactions between steroid signalling and neurotrophic factors in maintaining neuronal structure and function in vivo.

Acetylcholine↗

PubMedDate not supplied

Effects of 4-tert-octylphenol, 4-tert-butylphenol, and diethylstilbestrol on prenatal testosterone surge in the rat.

In the present study, we evaluated the effects that 4-tert-octylphenol (OP) and 4-tert-butylphenol (BP) had on the prenatal testicular testosterone surge at embryonic day (ED) 19.5 in the rat. In utero exposure to alkylphenols (0.1-100 mg/kg maternal weight) on EDs 13.5, 15.5, and 17.5 did not decrease testicular testosterone content, whereas exposure to diethylstilbestrol (DES) caused a significant depression in testosterone synthesis and secretion. The depression was maintained during ex vivo tissue culture. In order to elucidate the observed differences in the in vivo effects between alkylphenols and DES, the exposures were also carried out in tissue culture of intact ED 19.5 testes. Basal testosterone, progesterone, cAMP production and hCG-induced testosterone levels were determined during and after a 3-h culture period. DES (100 mg/l) did not alter testosterone production but caused a two-fold increase in progesterone. OP (10, 100, 500 mg/l) and BP (100 mg/l) significantly increased testosterone and progesterone levels by up to seven-fold. In the presence of BP 100 mg/l, however, the intratesticular testosterone content did not correlate with the significantly increased fraction of secreted, or leaked, testosterone. The latter was correlated with tissue damage observed at electron microscopic level. Consistent with this, BP 500 mg/l elevated testicular testosterone level slightly during the first hour in the culture but the level subsequently returned to the control value. At the electron microscopic level, alkylphenols caused most severe changes in Leydig cell membrane structures and lipid droplets. In the DES-treated testes, membrane vesicle formation around the lipid droplets and increased mitochondrial pleiomorphy were observed. Altogether, the present in vivo and in vitro analyses confirm different effects of alkylphenols and DES on fetal rat steroidogenesis and tissue structure.

Animals↗

PubMed1996

Zinc status and serum testosterone levels of healthy adults.

Zinc deficiency is prevalent throughout the world, including the USA. Severe and moderate deficiency of zinc is associated with hypogonadism in men. However, the effect of marginal zinc deficiency on serum testosterone concentration is not known. We studied the relationship between cellular zinc concentrations and serum testosterone cross-sectionally in 40 normal men, 20 to 80 y of age. In four normal young men (27.5 +/- 0.5 y), we measured serum testosterone before and during marginal zinc deficiency induced by restricting dietary zinc intake. We also measured serum testosterone in nine elderly men (64 +/- 9 y) who were marginally zinc deficient before and after 3 to 6 mo of supplementation with 459 mumol/ d oral zinc administered as zinc gluconate. Serum testosterone concentrations were significantly correlated with cellular zinc concentrations in the cross-sectional study (lymphocyte zinc versus serum testosterone, r = 0.43, p = 0.006; granulocyte zinc versus serum testosterone, r = 0.30, p = 0.03). Dietary zinc restriction in normal young men was associated with a significant decrease in serum testosterone concentrations after 20 weeks of zinc restriction (baseline versus post-zinc restriction mean +/- SD, 39.9 +/- 7.1 versus 10.6 +/- 3.6 nmol/L, respectively; p = 0.005). Zinc supplementation of marginally zinc-deficient normal elderly men for six months resulted in an increase in serum testosterone from 8.3 +/- 6.3 to 16.0 +/- 4.4 nmol/L (p = 0.02). We conclude that zinc may play an important role in modulating serum testosterone levels in normal men.

Adult↗

PubMed2002

Testosterone-induced vasorelaxation in the rat mesenteric arterial bed is mediated predominantly via potassium channels.

We have investigated the involvement of nitric oxide and K(+) channels in the vasorelaxant responses to physiologically-relevant concentrations of testosterone in the rat isolated mesenteric arterial bed. Testosterone (100 pM - 10 microM) elicited concentration-dependent relaxations in the isolated mesenteric arterial bed (pEC(50)=9.47 (9.22 - 9.73, 95% CI), maximal relaxation, R(max)=62.8+/-2.0%, n=6). A nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 300 microM) or removal of the endothelium significantly inhibited maximal relaxations to testosterone (L-NAME: R(max)=51.4+/-1.1%, P<0.01, n=6; endothelium-denuded: R(max)=46.9+/-2.8%, P<0.001, n=5). Raising the extracellular K(+) concentration to 30 and 60 mM, or pre-treatment with 300 microM tetrabutylammonium chloride (TBA), a calcium-activated K(+) channel inhibitor, abolished vasorelaxations induced by testosterone. A selective inhibitor of ATP-sensitive K(+) (K(ATP)) channels, glibenclamide (10 microM) and an inhibitor of voltage-sensitive K(+) (K(V)) channels, 4-aminopyridine (4-AP, 1 mM) did not affect testosterone-induced responses. Vasorelaxation to 1 microM testosterone was significantly (P<0.05) inhibited by 100 nM charybdotoxin (ChTx), an inhibitor of large conductance calcium-activated K(+) (BK(Ca)) channels (control: 63.3+/-9.9%, n=6; ChTx: 11.9+/-12.7%, n=3). Neither the testosterone receptor antagonist, flutamide (10 microM) nor an aromatase inhibitor, aminoglutethimide (10 microM) inhibited testosterone-induced responses. In conclusion, the present findings demonstrate, in the rat isolated mesenteric arterial bed, that testosterone causes acute vasorelaxations at physiologically relevant concentrations which are, in part, mediated via NO- and endothelium-dependent pathways. However, the activation of BK(Ca) channels plays a substantial role in testosterone-induced vasorelaxation.

Animals↗

PubMed2006

Non-genomic effect of testosterone on airway smooth muscle.

BACKGROUND AND PURPOSE: Recent studies on blood vessels have provided evidence that testosterone may exert direct effects on smooth muscle. However, an acute effect on airway reactivity has not been shown yet. The aim of this study was to assess the direct effect of testosterone on the responsiveness of male adult rabbit airway smooth muscle (ASM), precontracted with 10 microM acetylcholine, 10microM carbachol or 80 mM KCl. EXPERIMENTAL APPROACH: Contractility studies of rabbit tracheal smooth muscle were performed. KEY RESULTS: Testosterone at concentrations of or above 1 nM had a significant relaxant effect on ASM precontracted with acetylcholine or carbachol, but did not affect ASM precontracted with KCl. The mechanical removal of airway epithelium as well as the inhibition of NO synthetase (by 100microM L-NAME) reduced the relaxation caused by testosterone. The effect of testosterone was not altered by impairing prostanoid synthesis (by 10microM indomethacin). The nitric oxide donor, sodium nitroprusside, had the same relaxant effect on ASM precontracted with either carbachol or KCl. Inhibitors of androgen receptors (10microM flutamide) or DNA transcription (100microM actinomycin D) did not alter the effect of testosterone. Prolonged incubation of ASM with 100 nM or 100 microM testosterone for 24 or 48 h did not alter their responsiveness to acetylcholine. BSA-testosterone (1pM to 100nM) relaxed significantly ASM precontracted with carbachol. The mechanical removal of airway epithelium abolished the relaxant effect of BSA-testosterone. CONCLUSIONS AND IMPLICATIONS: Testosterone relaxes precontracted ASM via an epithelium and NO-mediated way. This effect is mediated via a non-genomic pathway.

Acetylcholine↗

PubMed2006

Epidemiology: testosterone and the metabolic syndrome.

Low levels of testosterone, hypogonadism, have several common features with the metabolic syndrome. In the Tromsø Study, a population-based health survey, testosterone levels were inversely associated with anthropometrical measurements, and the lowest levels of total and free testosterone were found in men with the most pronounced central obesity. Total testosterone was inversely associated with systolic blood pressure, and men with hypertension had lower levels of both total and free testosterone. Furthermore, men with diabetes had lower testosterone levels compared to men without a history of diabetes, and an inverse association between testosterone levels and glycosylated hemoglobin was found. Thus, there are strong associations between low levels of testosterone and the different components of the metabolic syndrome. In addition, an independent association between low testosterone levels and the metabolic syndrome itself has recently been presented in both cross-sectional and prospective population-based studies. Thus, testosterone may have a protective role in the development of metabolic syndrome and subsequent diabetes mellitus and cardiovascular disease in aging men. However, clinical trials are needed to confirm this assumption.

Blood Pressure↗

PubMed2006

Effect of testosterone on ex vivo vascular reactivity in man.

Testosterone is reported to have an acute vasodilating action in vitro, an effect that may impart a favourable haemodynamic response in patients with chronic heart failure. However, the effect of chronic testosterone exposure on general vascular reactivity is poorly described. In the present study, fresh subcutaneous resistance arteries were obtained from patients with heart failure (n=10), healthy controls (n=9) and men with androgen-deficiency (n=17). All arteries were studied using a wire myograph to examine the effect of cumulative additions of testosterone (1 nmol/l-100 micromol/l) compared with vehicle control following maximal pre-constriction with KCl (1-100 micromol/l). The vascular reactivity of arteries from androgen-deficient patients was examined further by recording tension concentration curves to cumulative additions of noradrenaline (1 nmol/l-100 micromol/l) and U46619 (1-300 nmol/l), followed by relaxation concentration curves to additions of ACh (acetylcholine; 10 nmol/l-30 micromol/l) and SNP (sodium nitroprusside; 10 nmol-30 micromol/l) respectively. In all cases, statistical analysis was performed by ANOVA. Patients with proven androgen-deficiency were treated according to clinical recommendations for a minimum of 3 months and further arteries (n=19) were taken for experimentation using the same protocol. In all groups, testosterone was confirmed to be an acute concentration-dependent vasodilator at concentrations > or =1 micromol/l (P=0.0001). The dilating effect of testosterone was augmented in patients with androgen-deficiency prior to treatment, and this effect was abrogated following appropriate testosterone replacement. Testosterone therapy significantly reduced the normal vascular dilating response to ACh and SNP (P<0.01) and significantly increased the contractile response to noradrenaline (P<0.01), but not U46619. Testosterone is an acute dose-dependent vasodilator of resistance arteries. Physiological testosterone replacement attenuates general vascular reactivity in androgen-deficient subjects. The numerous perceived benefits of testosterone replacement may be offset by a decline in vascular reactivity and, therefore, further studies and careful monitoring of patients is recommended.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1997

Testosterone concentrations and oligomenorrhea in women with acne.

BACKGROUND: Androgen excess is frequently associated with oligomenorrhea as well as acne. Oligomenorrhea in hirsute women has been demonstrated to be associated with higher active testosterone levels than found in eumenorrheic hirsute women. This study was designed to evaluate whether similar findings are present in women with acne. Forty-four consecutive women with acne were evaluated by measuring their levels of total testosterone, biologically active testosterone, and free testosterone. The women with oligomenorrhea and acne had significantly higher levels of biologically active testosterone than those with eumenorrhea and acne. This implies that biological active testosterone should be measured in oligomenorrheic women with acne and, if elevated, consideration should be given to antiandrogen therapy. METHODS: Data were collected from 44 consecutive Caucasian women aged 14 to 38 years. The patients were separated into two groups based on menstrual history. Group 1 had regular menses, and group 2 had oligomenorrhea, defined as menstrual intervals of greater than 36 days. All patients had blood samples drawn on their initial office visit, regardless of the phase of the menstrual cycle, and the levels of total testosterone (TT), biologically active testosterone (BT), and free testosterone (FT) were obtained. RESULTS: The serum TT level was 87 +/- 41.3 ng/dL (range, 31-150 ng/dL) in oligomenorrheic women and 56 +/- 27.5 ng/dL (range 8-107 ng/dL) in eumenorrheic women. There was no statistically significant difference. The serum BT level in oligomenorrheic women was 33 +/- 16.9 ng/dL (range, 11-51 ng/dL) and in eumenorrheic women 19 +/- 13.6 ng/dL (range, 11-51 ng/dL). This difference was statistically significant (p < 0.05). The serum FT level in oligomenorrheic women was 18 +/- 9.4 pg/mL (range, 1-29 pg/mL) and in eumenorrheic women 10 +/- 7.1 pg/mL (range, 1-32 pg/mL). This difference was not statistically significant (Table 1). CONCLUSIONS: Women with acne and oligomenorrhea, similar to women with hirsutism and oligomenorrhea, have higher levels of biologically active testosterone than those with normal menses.

Acne Vulgaris↗

PubMed1999

Is the measurement of serum testosterone routinely indicated in men with erectile dysfunction?

OBJECTIVE: To investigate the usefulness of serum testosterone levels as a relevant or useful indicator of sexual potency in men attending an erectile dysfunction clinic. PATIENTS AND METHODS: Ninety consecutive men attending the erectile dysfunction clinic completed a sexual-activity questionnaire, and underwent a focused physical examination and questioning about their medical history. The serum testosterone level was measured in all patients and the results analysed in relation to the patient's age. Patients with low serum testosterone levels commenced replacement therapy comprising three intramuscular injections of testosterone (Sustanontrade mark, Organon, The Netherlands) 250 mg every third week. Potency status and serum testosterone were reassessed after 3 months' treatment. RESULTS: Of the 90 men, 28 (31%) were aged < 50 years whilst 62 (69%) were >/=50 years old. Nineteen (21%) patients overall had low testosterone levels; four of these were < 50 and 15 were >/=50 years old. Five of 90 patients had a decreased libido; two of these also had low testosterone levels and all were < 50 years old. Testosterone levels returned to normal in all patients who received replacement therapy but potency returned in only two (10%); both were in the older group. CONCLUSION: Measuring testosterone was not helpful in assessing potency or libido and low serum levels were not related to age. Correcting low testosterone did not improve either impotence or libido.

Adult↗

PubMed2001

Testosterone perturbs epidermal permeability barrier homeostasis.

Although there are no known gender-related differences in permeability barrier function in adults, estrogens accelerate whereas testosterone retards barrier development in fetal skin, and male fetuses demonstrate slower barrier development than female littermates. Moreover, prenatal administration of the androgen receptor antagonist, flutamide, equalizes developmental rates in male and female fetuses. Therefore, we evaluated the effects of changes in testosterone on barrier homeostasis in adult murine and human skin. Hypogonadal mice (whether by castration or by treatment with systemic flutamide) displayed significantly faster barrier recovery at 3, 6, and 12 h than did controls, and testosterone replacement slowed barrier recovery in castrated mice. Moreover, testosterone directly effects the skin, as topical flutamide also accelerated barrier recovery in normal male mice. These findings appear to be of physiologic significance, since prepubertal male mice (age 5 wk) displayed accelerated barrier recovery in comparison with adult postpubertal (11 wk) males. These studies also appear to be relevant for humans, as a hypopituitary human subject demonstrated repeated changes in barrier recovery in parallel with peaks and nadirs in serum testosterone levels during intermittent testosterone replacement. Mechanistic studies showed that differences in epidermal lipid synthesis do not account for the testosterone-induced functional alterations. Instead, epidermal lamellar body (LB) formation and secretion both decrease, resulting in decreased extracellular lamellar bilayers in testosterone-replete animals. These studies demonstrate that fluctuations in testosterone modulate barrier function, and that testosterone repletion can have negative consequences for permeability barrier homeostasis.

Animals↗

PubMed1999

Pharmacokinetics of new testosterone transdermal therapeutic systems in gonadotropin-releasing hormone antagonist-suppressed normal men.

In a phase I single-center, open, randomized pilot study with a three-way cross-over design the pharmacokinetics of three testosterone-containing transdermal therapeutic systems were evaluated in healthy male volunteers. Testosterone TTS HEXAL type 1 and 2 are nonscrotal membrane patches differing in the kind of adhesive used. 6 subjects were treated with low dose Testosterone TTS type 1, high dose Testosterone TTS type 1 and low dose Testosterone TTS type 2. To eliminate the influence of endogenous serum testosterone, the endogenous testosterone secretion was suppressed by the GnRH antagonist cetrorelix. In all subjects under GnRH antagonist treatment a marked suppression of LH, FSH, testosterone, DHT and estradiol was observed. Physiologic testosterone levels were achieved during the 24-hour-application period. Maximal serum levels were reached after 4 hours with both TTS systems. Both systems appear suited for further testing because both enable a physiological circadian profile to be achieved. GnRH-antagonist pretreatment is a useful model to evaluate the effect of exogenous testosterone in clinical studies, when, due to fluctuations in endogenous hormone levels, an estimation of the proportion of exogenous steroid is not possible.

Administration, Cutaneous↗

PubMed2006

A clinical update on female androgen insufficiency--testosterone testing and treatment in women presenting with low sexual desire.

The diagnosis of female androgen deficiency syndrome is suggested by complaints of a diminished sense of well being, persistent unexplained fatigue and decreased sexual desire, sexual receptivity and pleasure in a woman who is oestrogen-replete and in whom no other significant contributing factors can be identified. The diagnosis is supported by the finding of low circulating concentrations of free testosterone. Barriers to its recognition include the non-specificity of the symptoms and methodological problems due to insensitive testosterone assays. Barriers to its treatment include the unavailability of satisfactory forms of testosterone for administration to women and lack of data regarding long-term safety. Although several conditions lead to clear-cut androgen deficiency, such as hypopituitarism, adrenal and ovarian insufficiency, glucocorticoid therapy and use of oral contraceptives and oral oestrogens, it is important for clinicians to recognise that in normal women, androgen levels decline by 50% from the early 20s to the mid 40s, and hence age-related androgen insufficiency may occur in women in their late 30s and 40s, as well as postmenopausally. Satisfactory measurements of free testosterone requires a sensitive and reliable assay for total testosterone, and quantitation of sex hormone binding globulin, from which free testosterone is readily calculated. Adverse effects of testosterone treatment are few if replacement is monitored to achieve physiological circulating testosterone concentrations. Currently, available methods include testosterone implants and testosterone creams, and transdermal patches and sprays are in development.

Androgens↗

PubMed1989

Promotion of murine hepatocarcinogenesis by testosterone is androgen receptor-dependent but not cell autonomous.

Tfm (testicular feminization) mutant mice lack functional androgen receptors. By studying liver tumor development in Tfm mice, we have shown that the greater susceptibility of male mice relative to female mice for liver tumor induction by N,N-diethylnitrosamine is androgen receptor-dependent. C57BL/6J normal and Tfm mutant mice were injected at 12 days of age with N,N-diethylnitrosamine (0.2 mumol/g, i.p.), and liver tumors were enumerated in 50-week-old animals. Normal males averaged 20 liver tumors per animal; Tfm males, 0.7; normal females, 0.6; and Tfm/+ heterozygous females, 1.5. The androgen receptor gene and the Tfm mutation are X chromosome linked. Because of random X chromosome inactivation, hepatocytes from Tfm/+ heterozygous female mice are mosaic with respect to the expression of mutant or wild-type receptors. To determine if testosterone acts directly as a liver tumor promoter, through the androgen receptor in preneoplastic hepatocytes, or by an indirect mechanism, we chronically treated these mosaic female mice with testosterone and measured the androgen receptor content of the resulting tumors. B6C3F1 Tfm/+ mosaic and +/+ wild-type female mice were injected i.p. at 12 days of age with N,N-diethylnitrosamine (0.1 mumol/g) and ovariectomized at 8 weeks of age. Half of the mice of each group subsequently received biweekly s.c. injections of testosterone (0.15 mg per mouse) for 30 weeks. Tumor multiplicity was the same for wild-type and Tfm/+ mosaic females treated with testosterone (31-32 tumors per animal at 38 weeks of age) and was increased relative to females not treated with testosterone (13-17 tumors per animal at 50 weeks of age). Testosterone treatment did not significantly increase the percentage of androgen receptor-positive tumors in Tfm/+ mosaic females: 58% of the tumors from Tfm/+ mosaic females treated with testosterone were receptor positive compared to 48% in Tfm/+ females not treated with testosterone and 92% in wild-type females treated with testosterone. Finally, the number of androgen receptors in the majority of liver tumors examined was greatly decreased relative to the surrounding normal liver tissue. We conclude that liver tumor promotion by testosterone requires a functional androgen receptor in the intact animal. However, this promotion is not cell autonomous; that is, the response of the preneoplastic hepatocyte is not dependent on the expression of functional receptor in the target cell.

Aging↗

PubMed1995

Long-lived testosterone esters in the rat.

Over the past decade it has become increasingly clear that steroid hormones are enzymatically esterified with fatty acids. These steroidal esters are the natural analogs of synthetic esters that are used therapeutically. One such family of pharmacological steroids is the synthetic alkyl esters of testosterone, androgens with great hormonal potency. We have investigated whether testosterone esters exist naturally by using the rat as a model. Most tissues of male rats, including blood, have very little if any ester (quantified by immunoassay as a nonpolar saponifiable metabolite), but fat and testes have sizable quantities, approximately 3 ng of testosterone equivalents per g of tissue. Testosterone in fat averages 9 ng/g. The fat from female rats and long-term (> 2 weeks) castrated males has no detectable testosterone ester. The presence of testosterone esters was confirmed by GC/MS, which clearly showed the presence of testosterone in the hydrolyzed ester fraction of fat from intact males but not long-term castrates. Upon castration, testosterone levels in the fat completely disappear within 6 hr. To the contrary, it is not until 48 hr after castration that a measurable fall in the testosterone ester fraction was observed; even after 10 days a small amount of ester is still present in the fat. These experiments demonstrate the existence of a previously unknown androgen with a potentially important physiological impact; testosterone esters, natural analogs of potent therapeutic agents, occur in the fat where they can serve as a reservoir of preformed androgen to stimulate neighboring target tissues.

Adipose Tissue↗

PubMed2006

Elevated testosterone induces apoptosis in neuronal cells.

Testosterone plays a crucial role in neuronal function, but elevated concentrations can have deleterious effects. Here we show that supraphysiological levels of testosterone (micromolar range) initiate the apoptotic cascade. We used three criteria, annexin V labeling, caspase activity, and DNA fragmentation, to determine that apoptotic pathways were activated by testosterone. Micromolar, but not nanomolar, testosterone concentrations increased the response in all three assays of apoptosis. In addition, testosterone induced different concentration-dependent Ca2+ signaling patterns: at low concentrations of testosterone (100 nm), Ca2+ oscillations were produced, whereas high concentrations (1-10 microm) induced a sustained Ca2+ increase. Elevated testosterone concentrations increase cell death, and this effect was abolished in the presence of either inhibitors of caspases or the inositol 1,4,5-trisphosphate receptor (InsP3R)-mediated Ca2+ release. Knockdown of InsP3R type 1 with specific small interfering RNA also abolished the testosterone-induced cell death and the prolonged Ca2+ signals. In contrast, knockdown of InsP3R type 3 modified neither the apoptotic response nor the Ca2+ signals. These results support our hypothesis that elevated testosterone alters InsP3R type 1-mediated intracellular Ca2+ signaling and that the prolonged Ca2+ signals lead to apoptotic cell death. These effects of testosterone on neurons will have long term effects on brain function.

Annexin A5↗

PubMed2005

The inverse relationship between thoracic aortic intima media thickness and testosterone level.

BACKGROUND: It is known that testosterone prevents coronary artery disease, and lower testosterone level is a risk factor for ischemic heart disease in men. However, there is no report showing the relationship between testosterone level and severity of thoracic aortic atherosclerosis. AIM: To investigate whether a relationship exists between atherosclerotic thoracic aortic intima media thickness (TAIT) and testosterone level. METHOD: Forty-two male patients (mean age 56 +/- 12 years) without a history of atherosclerotic cardiovascular disease referred for transesophageal echocardiography (TEE) were included. Intima media thickness of aorta was evaluated in each patient by using TEE. Testosterone levels were measured using a commercial kit. Blood chemistry parameters were measured by automated analyzers. The data obtained was evaluated by using correlation analyses and linear regression analysis tests. RESULTS: Mean testosterone values were 507 +/- 209 ng/dl. Testosterone levels showed a negative significant correlation with TAIT (r = -765, p < 0.001). In addition, testosterone levels showed positive correlations with albumin (r = 0.690, p = 0.019) and negative correlations with uric acid (r = -0.630, p < 0.001), HsCRP (r = -0.449, p = 0.003), fibrinogen (r = -0.508, p = 0.001), and white blood cells (r = -0.433, p = 0.005). On the other hand, multiple linear regression analysis showed that TAIT was independently associated with testosterone and uric acid (beta = -0.610, p = 0.002 versus beta = 0.409, p = 0.026 respectively). CONCLUSION: This study indicates that there is an independent relationship between testosterone and TAIT.

Adult↗

PubMedDate not supplied

Testosterone ethosomes for enhanced transdermal delivery.

Physiological decrease in testosterone levels in men with age causes various changes with clinical significance. Recent testosterone replacement therapy is based mainly on transdermal nonpatch delivery systems. These products have the drawback of application on extremely large areas to achieve required hormone blood levels. The objective of the present study was to design and test a testosterone nonpatch formulation using ethosomes for enhanced transdermal absorption. The ethosomal formulation was characterized by transmission electron microscopy and dynamic light scattering for structure and size distribution and by ultracentrifugation for entrapment capacity. To evaluate the feasibility of this delivery system to enhance testosterone permeation through the skin, first the systemic absorption in rats was compared with a currently used gel (AndroGel). Further, theoretical estimation of testosterone blood concentration following ethosomal application in men was made. For this purpose, in vitro permeation experiments through human skin were performed to establish testosterone skin permeation values. In the design of these experiments, testosterone solubility in various solutions was measured and the effect of the receiver medium on the skin barrier function was assessed by confocal laser scanning microscopy. Theoretical estimation shows that testosterone human plasma concentration value in the upper part of the physiological range could be achieved by application of the ethosomal formulation on an area of 40 cm(2). This area is about 10 times smaller than required with current nonpatch formulations. Our work shows that the ethosomal formulation could enhance testosterone systemic absorption and also be used for designing new products that could solve the weaknesses of the current testosterone replacement therapies.

Animals↗

PubMed2004

Testosterone therapy in erectile dysfunction.

Studies in animals have indicated that the nitric oxide erectile pathway is testosterone-dependent. Castration induces erectile dysfunction and a reduction in nitric oxide synthase-stained nerves in erectile tissue. Furthermore, castration adversely affects penile hemodynamics and smooth muscle content, leading to veno-occlusive dysfunction. Testosterone replenishment reverses these physiological, biochemical and structural changes. Several clinical studies have demonstrated the benefits of a combination of testosterone and sildenafil. A recently published, multicenter study evaluated the safety and efficacy of testosterone gel 1% (Testogel; Schering AG, Germany/AndroGel; Solvay Pharmaceuticals) vs. placebo gel in conjunction with sildenafil, in producing an erectile response in hypogonadal men who did not respond to treatment with sildenafil alone for erectile dysfunction. The selection criteria required subjects to have had erectile dysfunction for at least 3 months, to be non-responsive to 100 mg sildenafil and to have low testosterone levels (< 400 ng/dl). The primary efficacy measurement was the mean change from baseline in the Erectile Function domain of the International Index of Erectile Function (IIEF). Secondary outcome measures included the mean change from baseline in the other domains and the total sum of the IIEF. Subjects were randomized to receive either testosterone gel + sildenafil, or placebo gel + sildenafil for 12 weeks. Testosterone therapy with testosterone gel improved the erectile response to sildenafil. Therefore, testosterone therapy may be considered for the treatment of erectile dysfunction in men with low to low-normal testosterone levels, who have failed prior treatment with sildenafil alone. Consequently, it is important to screen for hypogonadism in men who fail PDE5 inhibitors.

Androgens↗