Exogenous testosterone therapy on choroid in androgen deficiency

AIM:To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency.METHODS:Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers were included in the study.The eyes were scanned for subfoveal choroidal thickness(SFCT),choroidal vascularity index(CVI),choroidstromal area(C-SA),choroid-luminal area(C-LA),choroidstromal to luminal area ratio(CSLR),and the choroidal parameters within central 1500μm of the macula(CVI1500,C-LA1500,C-SA1500,and CSLR1500)by enhanced-depth imaging optical coherence tomography(EDI-OCT)at baseline,6th and 18th weeks of the exogenous testosterone treatment.RESULTS:The mean SFCT values of the androgen deficient groups and healthy controls were 307.7±27.0 and 303.2±37.2μm(P=0.8).However,CVI,C-SA,CSLR,CVI1500,C-LA1500,and CSLR1500 were significantly different between the groups(all P<0.01).At the 6th week visit after exogenous testosterone treatment,SFCT,CVI,C-LA,and C-SA were significantly decreased,and these parameters returned to baseline levels at the 18th-week visit(all P>0.05).However,CVI1500 and LA1500 significantly increased at the end of the follow-up period(P<0.001).CONCLUSION:CVI is lower in androgen-deficient patients than in healthy subjects.The alterations in the choroid during the testosterone peak are transient in the treatment of patients with androgen deficiency.However,the increase in CVI within the central 1500μm of the macula persists even after 4mo.

Assessment of spermatogenesis in camels via seminiferous tubule staging and testosterone profiling

Objective:To investigate the successive morphological stages of spermatogenesis,hormonal regulation,and testosterone profile in dromedary camel reproduction.Methods:Testicular tissue samples were obtained from 12 dromedary bull camels aged 7 to 8 at a local abattoir.The histological assessment involved tissue processing,hematoxylin and eosin(H&E)staining,and examination under a microscope.Stereological analysis,germ cell identification,and assessment of seminiferous tubules and maturation were conducted.Testosterone assay was performed by radioimmunoassay using blood samples collected at regular intervals.Results:The study revealed 12 phases of the dromedary camel's seminiferous epithelium cycle,highlighting distinct morphological characteristics and cellular processes.Acrosomal migration,maturation,cap formation,and the Golgi-mediated synthesis of proacrosomal vesicles were also explained in dimension,as were the steps of acrosome biogenesis.Spermatids and mature sperm cells were present when spermatogenesis phases were examined.An analysis of the dimensions of seminiferous tubules revealed specific measures for diameter,area,and epithelial height about luminal characteristics.Moreover,there were noticeable variations in the serum testosterone concentrations during the study period,indicating temporal dynamics.Conclusions:This study outlines the spermatogenesis process in dromedary camels across 12 stages,emphasizing cellular dynamics and acrosomal biogenesis.It also provides seminiferous tubule measurements and observes seasonal testosterone fluctuations,offering insights into reproductive regulation and potential strategies for camel breeding conservation.

Adiponectin orchestrates testosterone suppression in biological pathways

This current review highlights adiponectin engagement with AdipoR1 and AdipoR2 which subsequently triggers pathways such as AMPK,PPARα,and MAPK,thereby modulating testicular steroidogenesis.Adiponectin's actions on Leydig and adrenal cells inhibit androgen secretion by suppressing the steroidogenic acute regulatory protein(StAR).Given that StAR facilitates cholesterol to testosterone conversion,AMPK inhibits this process by modulating cholesterol transport and suppressing StAR expression through multiple avenues.Furthermore,adiponectin-induced PPARαactivation impedes mitochondrial cholesterol influx,further modulating androgen biosynthesis.The suppressive influence of PPARαon steroidogenic genes,notably StAR,is evident.Collectively,adiponectin signalling predominantly attenuates androgen production,ensuring metabolic and reproductive equilibrium.Imbalances,as seen in conditions like hypogonadism and obesity-related infertility,highlight their crucial roles and potential clinical interventions for reproductive disorders.

Effect of sodium arsenite on spermatogenesis, plasma gonadotrophins and testosterone in rats

To investigate the effect of arsenic on spermatogenesis. Methods: Mature (4 months old) Wistar rats were intraperitoneally administered sodium arsenite at doses of 4, 5 or 6 mg-kg^-day1 for 26 days. Different varieties of germ cells at stage VII seminiferous epithelium cycle, namely, type A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatocytes (mPSc) and step 7 spermatids (7Sd) were quantitatively evaluated, along with radioimmunoassay of plasma follicle-stimulating hormone (FSH), lutuneizing hormone (LH), testosterone and assessment of the epididymal sperm count. Results: In the 5 and 6 mg/kg groups, there were significant dose-dependent decreases in the accessory sex organ weights, epididymal sperm count and plasma concentrations of LH, FSH and testosterone with massive degeneration of all the germ cells at stage VII. The changes were insignificant in the 4 mg/kg group. Conclusion: Arsenite has a suppressive influence on spermatogenesis and gonadotrophin and testosterone release in rats.

Lowered testosterone in male obesity： mechanisms, morbidity and management

With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular （HPT） axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen deficiency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials.

The relationship between sleep disorders and testosterone in men

Plasma testosterone levels display circadian variation, peaking during sleep, and reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with pulses every 90 min reflecting the underlying rhythm of pulsatile luteinizing hormone （LH） secretion. The increase in testosterone is sleep, rather than circadian rhythm, dependent and requires at least 3h of sleep with a normal architecture. Various disorders of sleep including abnormalities of sleep quality, duration, circadian rhythm disruption, and sleep-disordered breathing may result in a reduction in testosterone levels. The evidence, to support a direct effect of sleep restriction or circadian rhythm disruption on testosterone independent of an effect on sex hormone binding globulin （SHBG）, or the presence of comorbid conditions, is equivocal and on balance seems tenuous. Obstructive sleep apnea （OSA） appears to have no direct effect on testosterone, after adjusting for age and obesity. However, a possible indirect causal process may exist mediated by the effect of OSA on obesity. Treatment of moderate to severe OSA with continuous positive airway pressure （CPAP） does not reliably increase testosterone levels in most studies. In contrast, a reduction in weight does so predictably and linearly in proportion to the amount of weight lost. Apart from a very transient deleterious effect, testosterone treatment does not adversely affect OSA. The data on the effect of sleep quality on testosterone may depend on whether testosterone is given as replacement, in supratherapeutic doses, or in the context abuse. Experimental data suggest that testosterone may modulate individual vulnerability to subjective symptoms of sleep restriction. Low testosterone may affect overall sleep quality which is improved by replacement doses. Large doses of exogenous testosterone and anabolic/androgenic steroid abuse are associated with abnormalities of sleep duration and architecture.

Changes in aortic endothelium ultrastructure in male rats following castration, replacement with testosterone and administration of 50α-reductase inhibitor

Aim： To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods： Forty-eight male Sprague-Dawley rats were randomly divided into four groups： group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone （T） undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T （FT） and dihydrotestosterone （DHT） were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score （VESS） was computed. Results： Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups （P 〈 0.01）; DHT concentrations of group D rats were significantly decreased （P 〈 0.01 ） when compared with those of groups A and C. Rats in groups B and D rats （with low androgen levels） had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion： These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.

Effects of varicocele on testosterone, apoptosis and expression of StAR mRNA in rat Leydig cells

The aim of this study was to explore the effects of varicocele on the morphology and function of Leydig cells in the rat testis. Forty male Sprague-Dawley rats were divided into two groups： the experimental group underwent surgery to create a left varicocele （VC）, and the control group underwent a sham operation. Serum testosterone and intratesticular testosterone levels were measured using a radioimmunoassay after 4 and 8 weeks of operation. Leydig cells were studied for apoptosis and expression of steroidogenetic acute regulatory （STAR） protein mRNA levels. Serum testosterone levels declined after 4 and 8 weeks of operation but were not significant （P〉0.05）. However, the intratesticular testosterone levels after 8 weeks were significantly decreased compared with the control group （P〈0.01）. The mean apoptosis index of Leydig cells in the experimental group was significantly higher than that in the control group after 4 or 8 weeks （P〈0.01）. StAR mRNA levels in the Leydig cells of the experimental group were significantly lower compared to those of the control group （P〈0.01）. Our data show that varicocele did impair Leydig cell function by increasing apoptosis and suppressing the expression of the StAR protein.

Quantitative (stereological) study of incomplete spermatogenic suppression induced by testosterone undecanoate injection in rats

Aim: To evaluate the key lesions in spermatogenesis suppressed partially by testosterone undecanoate (TU) treatment. Methods: Adult male SD rats were treated with vehicle or TU (19 mg/kg) injection (i.m.) every 15 days for 130 days. The numbers of all types of cells (nuclei) in the seminiferous tubules and the interstitial tissue were estimated using a contemporary stereological tool, the optical disector. Results: In response to TU treatment, the numbers of non-type B spermatogonia, type B spermatogonia and late elongated spermatids per testis were reduced to 51 %, 66 % and 14 % of the controls, respectively. The conversion ratios from type B spermatogonia to early spermatocytes and pachytene spermatocytes were not significantly affected and the ratios to the later germ cell types fell to 51 % - 65 % of the controls. Less than 1.0 % of immature round spermatids were seen sloughing into the tubule lumen, 4.0 % of elongated spermatids retained in the seminiferous epithelium, and about half of the elongated spermatid nuclei appreciably malformed. Leydig cells were atrophied but their number and the peritubular myoid cell number per testis were unchanged. Conclusion: Double inhibition of spermatogenesis (i.e. inhibition at spermiation and spermatogonial conversion to type B spermatogonia), a scenario seen in the monkey and human following gona-dotrophin withdrawal, was not sufficiently effective for a complete spermatogenic suppression in the rat after TU treatment, probably due to ineffective inhibition of the Leydig cell population and therefore the intra-testicular testosterone levels.

Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus： a systematic review and meta-analysis of randomized controlled trials

This systematic review was aimed at assessing the metabolic effects of testosterone replacement therapy （TRT） on hypogonadal men with type 2 diabetes mellitus （T2DM）. A literature search was performed using the Cochrane Library, EMBASE and PubMed. Only randomized controlled trials （RCTs） were included in the meta-analysis. Two reviewers retrieved articles and evaluated the study quality using an appropriate scoring method. Outcomes including glucose metabolism, lipid parameters, body fat and blood pressure were pooled using a random effects model and tested for heterogeneity. We used the Cochrane Collaboration＇s Review Manager 5.2 software for statistical analysis. Five RCTs including 351 participants with a mean follow-up time of 6.5months were identified that strictly met our eligibility criteria. A meta-analysis of the extractable data showed that testosterone reduced fasting plasma glucose levels （mean difference （MD）. -1.10; 95% confidence interval （CI） （-1.88, -0.31））, fasting serum insulin levels （MD： -2.73; 95% CI （-3.62, -1.84））, HbAlc % （MD.. -0.87; 95% CI （-1.32, -0.42）） and triglyceride levels （MD： -0.35; 95% CI （-0.62, -0.07））. The testosterone and control groups demonstrated no significant difference for other outcomes. In conclusion, we found that TRT can improve glycemic control and decrease triglyceride levels of hypogonadal men with T2DM. Considering the limited number of participants and the confounding factors in our systematic review; additional large, well-designed RCTs are needed to address the metabolic effects of TRT and its long-term influence on hypogonadal men with T2DM.

The testosterone mimetic properties of icariin

Aim： To evaluate the testosterone mimetic properties of icariin. Methods： Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each： the control group （C）, the model group （M）, the icariin group （ICA） and the testosterone group （T）. The reproductive system was damaged by cyclophosphamide （intraperitoneal injection, 20 mg/kg·day） for 5 consecutive days for groups M, ICA and T, at the sixth day, ICA （gastric gavage, 200 mg/kg·day） for the ICA group and sterandryl （subcutaneous injection, 5 rag/rat.day） for the T group for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone （LH）, follicle stimulating hormone （FSH）, serum bone Gla-protein （BGP） and tartrate-resistant acid phosphatase activity in serum （StrACP） were determined. The histological changes of the testis and the penis were observed by microscope with hematoxylin-eosin （HE） staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling （TUNEL）, respectively. Results： （1） Icariin improved the condition of reproductive organs and increased the circulating levels of testosterone. （2） Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption. （3） Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells. Conclusion： Icariin has testosterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.

Reversible effect of testosterone undecanoate injection on spermatogenesis in rats

Aim: To study the effect of testosterone undecanoate (TU) injection on spermatogenesis in rats. Methods:Twenty adult SD rats received vehicle or TU (8 mg/kg, 19 mg/kg or 625 mg/kg) injection, im, every 15 days for 60days, and another 38 animals received similar treatments for 130 days with half of them undergoing a recovery phase of120 days (5 rats for each treatment). At the end of the treatment, testes were removed and the diameter of the seminif-erous tubules and the number of late elongated spermatids (steps 15-19) per testis were estimated with stereologicalmethods as a measure of the spermatogenic efficiency. Results: Low dose (8 mg/kg) TU treatment virtually hadno effect on spermatogenesis. A dose of 19 mg/kg slightly suppressed spermatogenesis 60 days after treatment, and se-vere suppression occurred after another 70 days of dosing. Spermatogenesis was completely recovered at the end of therecovery phase. Large dose (625 mg/kg) TU treatment did not significantly affect spermatogenesis and was well toler-ated by animals. Conclusion: TU injection reversibly suppresses spermatogenesis in rats.

Testosterone level and mortality in elderly men wit systolic chronic heart failure

Previous studies on the prognostic significance of serum levels of androgens in patients with chronic heart failure （CHF） have yielded conflicting results. The aim of this study was to examine the relationship between serum concentration of testosterone and mortality in men with systolic CHF. A total of 175 elderly men （age ≥60 years） with CHF were recruited. Total testosterone （TI＇） and sex hormone-binding globulin （SHBG） were measured, and estimated free testosterone （eFT） was calculated. The median follow-up time was 3.46 years. Of these patients, 17 had a TT level below 8 nmol I^-1 （230 ng dI^-1）, 27 had an eFT level below 0.225 nmol I^-1 （65 pg ml^-1） and 12 had both. Using the age-specific tenth percentiles of TT and eFT in healthy men in our laboratory as cutoff points, the prevalences of TT and eFT deficiency was 21.7% （38/175） and 27.4% （48/175）, respectively. Both TT and eFT were inversely associated with left ventricular ejection fraction （LVEF） and N-terminal pro-brain natriuretic peptide （NT-pro-BNP） （all P〈0.01）. Kaplan-Meier curves for patients in low, medium and high tertiles according to TT and eFT level showed significantly different cumulative survival rate （both P〈0.01 by log-rank test）. However, after adjustment for clinical variables, there were no significant associations of either TT or eFT levels with survival time （0R=0.97, 95% CI： 0.84-1.12, P=0.28 and 0R=0.92, 95% CI： 0.82-1.06, P=0.14, respectively）. Our study showed that levels of TT and eFT are commonly decreased in elderly patients with systolic CHF and related to disease severity, but they are not independent predictors for mortality.

Impact of the association between elevated oestradiol and low testosterone levels on erectile dysfunction severity

Our aim was to assess the impact of the association between elevated oestradiol （E2） and low testosterone （T） levels on erectile dysfunction （ED） severity. A total of 614 male patients with ED and a normal or low T level in association with normal or elevated E2 levels were enrolled. Patients underwent routine laboratory investigations in addition to measurements of total T, total E2, follicle-stimulating hormone （FSH）, luteinizing hormone （LH） and prolactin. We compared the responses to the erectile function domain, Q3 （achieving erection） and Q4 （maintaining erection） of the International Index for Erectile Function （IIEF） score in patients with the following： normal T and E2 levels; low T level; low T level and elevated E2 level; and elevated E2 level. Of the patients included, 449 （73.1%） had normal T and E2 levels, 110 （17.9%） had a low T level, 36 （5.9%） had a low T level and an elevated E2 level, and 19 （3.1%） had an elevated E2 level. Increased ED severity was significantly associated with low T levels, elevated E2 levels, and both a low T level and an elevated E2 level. Additionally, the mean values of the EF-domain, Q3 and Q4 were significantly lower in patients with both a low T level and an elevated E2 level compared to patients with any condition alone. In conclusion, a low T level had the primary effect on erectile function; however, a concomitantly elevated E2 level had an additive impairment effect.

Testosterone deficiency：a historical perspective

The biological effects of the testes and testosterone are known since antiquity. Aristotle knew the effects of castration and his hypothesis on fertilization is one of the first scientific encounters in reproductive biology. Over centuries, castration has been performed as punishment and to produce obedient slaves, but also to preserve the soprano voices of prepubertal boys. The Chinese imperial （and other oriental） courts employed castrates as overseers in harems who often obtained high-ranking political positions. The era of testis transplantation and organotherapy was initiated by John Hunter in London who transplanted testes into capons in 1786. The intention of his experiments was to prove the ＇vital principle＇ as the basis for modern transplantation medicine, but Hunter did not consider endocrine aspects. Arnold Adolph Berthold postulated internal secretion from his testicular transplantation experiments in 1849 in Gottingen and is thus considered the father of endocrinology. Following his observations, testicular preparations were used for therapy, popularized by self-experiments by Charles-Edouard Brown-Sequard in Paris （1889）, which can at best have placebo effects. In the 1920s Sergio Voronoff transplanted testes from animals to men, but their effectiveness was disproved. Today testicular transplantation is being refined by stem cell research and germ cell transplantation. Modern androgen therapy started in 1935 when Enrest Lacquer isolated testosterone from bull testes in Amsterdam. In the same year testosterone was chemically synthesized independently by Adolf Butenandt in G6ttingen and Leopold Ruzicka in Basel. Since testosterone was ineffective orally it was either compressed into subcutaneous pellets or was used orally as 17α-methyl testosterone, now obsolete because of liver toxicity. The early phases of testosterone treatment coincide with the first description of the most prominent syndromes of hypogonadism by Klinefelter, by Kallmann, DelCastillo and Pasqualini. In the 1950s longer-acting injectable testosterone enanthate became the preferred therapeutic modality. In the 1950s and 1960s, research concentrated on the chemical modification of androgens in order to emphasize their anabolic effects. Although anabolic steroids have largely disappeared from clinical medicine, they continue to live an illegal life for doping in athletics. In the 1970s the orally effective testosterone undecanoate was added to the spectrum of preparations. Recent transdermal gels and long-acting injectable preparations provide options for physiological testosterone substitution therapy.

Testosterone and cardiovascular disease in men

Despite regional variations in the prevalence of coronary artery disease （CAD）, men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are implicated in this inequality. This ＇Perspectives＇ article reviews the current evidence regarding the cardiovascular effects of testosterone in men including an examination of the age-related decline in testosterone, the relationship between testosterone levels and coronary disease, coronary risk factors and mortality. We also review the vaso-active effects of testosterone, and discuss how these have been used in men with heart failure and angina. We discuss the ＇cause＇ versus ＇effect＇ controversy, regarding low testosterone levels in men with coronary heart disease, as well as concerns over the use of testosterone replacement therapy in middle aged and elderly men. The article concludes with a discussion regarding the future direction for work in this interesting area, including the relative merits of screening for, and treating hypogonadism with testosterone replacement therapy in men with heart disease.

Effects of testosterone replacement and its pharmacogenetics on physical performance and metabolism

In men, testosterone （T） deficiency is associated with decreased physical performance, as defined by adverse traits in body composition, namely increased body fat content and reduced muscle mass. Physical abilities in androgen-deficient men are further attenuated by lower oxygen supply due to decreased hemoglobin concentrations and by poor glucose utilization. Dysthymia and a lack of necessary aggressiveness also contribute to deteriorate physical effectiveness. Substitution of T can improve lipid and insulin metabolism as well as growth of muscle fibers and decreasing fat depots, which consequently will result in changes of body composition. Increment of bone density will further contribute to increase physical fitness. The effects of T replacement therapy （TRT） are strongly influenced by age, training, and also pharmacogenetics： the CAG repeat polymorphism in exon 1 of the androgen receptor （AR） gene modulates androgen effects. In vitro, transcription of androgen-dependent target genes is attenuated with increasing length of triplet residues, Clinically, the CAG repeat polymorphism causes significant modulations of androgenicity in healthy eugonadal men as well as efficacy of TRT. Thresholds at which T treatment should be initiated, as well as androgen dosage, could be tailored according to this polymorphism.

Endocrine milieu and erectile dysfunction： is oestradio-testosterone imbalance, a risk factor in the elderly？

Oestrogens are not exclusive to the female gender but occur in moderate circulating levels of 25-70 pg ml^-1 in men, compared to 44- 153 pg ml^-1 in women. Arising from aromatisation of testosterone （T）, oestrogen is considered to have many opposing physiological functions and the progressive T decline in the aging male is associated with relative and/or absolute increase in serum oestradiol （E2）. Sexual disinterest and erectile dysfunction （ED） in the elderly may well be due to pathophysiological E2-T imbalance; the altered hormonal ratio may also explain the higher incidence of ED in hyperestrogenism or following exposure to environmental/plant oestrogens.

Relationship between testosterone and indexes indicating endothelial function in male coronary heart disease patients

Aim： To investigate the relationship between androgen level and the indexes indicating endothelial function in male patients with coronary heart disease （CHD）. Methods： We registered the following data for 106 50-70-year-old men： age, weight, blood lipid, including total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride, whether a smoker, sugar levels, blood pressure, free testosterone （FT）, vascular cell adhesion molecule- 1 （VCAM- 1） and the intima-media thickness （IMT） of common carotid artery, common carotid diameter, maximum velocity in systolic phase, minimum velocity in diastolic phase and resistent index. Among the 106 men, 51 were patients with CHD. The relationships between FT level, VCAM-1 concentration and IMT were examined, respectively, using a stepwise linear regression technique among all the 106 men. Results： There was no statistical difference in terms of age, blood pressure, whether a smoker, sugar levels, HDL-C, minimum velocity in diastolic phase, resistent index between male CHD patients and controls; whereas results for weight, total cholesterol, low density lipoprotein cholesterol, triglyceride, VCAM- 1 and IMT of male CHD patients were higher than those of controls; FT level and maximum velocity in systolic phase were lower. It was found that among all the objects, FT level was inversely correlated with IMT and VCAM-1 concentration. Condusion： FT level was inversely correlated with VCAM-I concentration and IMT which are indicators of endothelial function. （Asian JAndro12008 Mar; 10： 214-218）

More than eight years＇ hands-on experience with the novel long-acting parenteral testosterone undecanoate

Testosterone （T） as a compound for treatment of T deficiency has been available for almost 70 years, but the pharmaceutical formulations have been less than ideal. Traditionally, injectable T esters have been used for treatment, but they generate supranormal T levels shortly after the 2-3 weekly injection interval. T levels then decline very rapidly, becoming subnormal during the days preceding the next injection. The rapid fluctuations in plasma T are subjectively experienced as disagreeable. T undecanoate （TU） is a new injectable T preparation with a considerably better pharmacokinetic profile. After two initial injections separated by a 6-week interval, the following intervals between two injections are generally 12 weeks, eventually amounting to a total of four injections per year. Plasma T levels with this preparation are nearly always in the range of normal men, as are its metabolic products estradiol and dihydrotestosterone （DHT）. It reverses the effects of hypogonadism on bone and muscle and metabolic parameters, and on sex functions. It is suitable for male contraception. Its safety profile is excellent because of the continuous normalcy of plasma T levels. No polycythemia has been observed and no adverse effects on lipid profiles. Prostate safety parameters are well within reference limits. TU is a valuable treatment option of androgen deficiency.