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.

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.

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.

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.

Effects of Melandrium firmum methanolic extract on testosterone-induced benign prostatic hyperplasia in Wistar rats

Benign prostatic hyperplasia （BPH） is an age-related disease of unknown aetiology characterized by prostatic enlargement coincident with distinct alterations in tissue histomorphology. Instead of therapeutic agents that can cause severe side effects, plant extracts are frequently used to treat BPH. In this study, we investigated whether the Melandrium firmum methanolic extract （MFME） improves BPH, using the testosterone propionate （TP）-induced BPH rat model. Castration was performed via the scrotal route under sodium pentobarbital anaesthesia. BPH in castrated rats was generated via daily subcutaneous injections of TP （3 mg kg-1） dissolved in corn oil, for 4 weeks. MFME was administered daily by oral garage at a dose of 200 mg kg-1 for 4 weeks, along with the TP injections. The control group received injections of corn oil subcutaneously. At the scheduled termination of the experiment, all rats were killed and their prostates weighed; the relative prostate weight （prostate/body weight ratio） was calculated, and histomorphological changes in the prostate were examined. Additionally, we measured the levels of testosterone and dihydrotestosterone （DHT） in the serum and the prostate. Experimentally induced BPH led to marked decreases in the relative prostate weight and the DHT levels in the serum and the prostate. Histologically, BPH was evident in the ventral lobe of the prostate, and MFME treatment suppressed the severity of the lesions. These results indicate that MFME effectively inhibits the development of BPH induced by testosterone in a rat model. Further studies will be needed to identify the compound（s） responsibility for inducing the protective effect against BPH and determine its mechanism of action,

Inverse relationship between bioavailable testosterone and subclinical coronary artery calcification in non-obese Korean men

Although low testosterone levels in men have been associated with high risk for cardiovascular disease, little is known about the association between male sex hormones and subclinical coronary disease in men with apparently low cardiometabolic risk. This study was performed to investigate the association between male sex hormones and subclinical coronary artery calcification measured as coronary calcium score in non-obese Korean men. We examined the relationship of total testosterone, sex hormone-binding globulin, bioavai lable testosterone and free testosterone with coronary calcium score in 291 non-obese Korean men （mean age： 52.8--- 9.3 years） not having a history of cardiovascular disease. Using multiple linear regression, we evaluated associations between log （sex hormone） levels and log （coronary calcium score） after adjusting for confounding variables in 105 men with some degree of coronary calcification defined as coronary calcium score ~〉 1. In multiple linear regression analysis, bioavailable testosterone was inversely associated with coronary calcium score （P=0.046） after adjusting for age, body mass index, smoking status, alcohol consumption, regular exercise, mean blood pressure, resting heart rate, C-reactive protein, fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein （HDL） cholesterol, hypertension medication and hyperlipidernia medication, whereas total testosterone, sex hormone-binding globulin and free testosterone were not （P=0.674, P=O. 121 and P=O. 102, respectively）. Our findings indicate that bioavailable testosterone is inversely associated with the degree of subclinical coronary artery calcification in non-obese men.

Effect of long-acting testosterone undecanoate treatment on quality of life in men with testosterone deficiency syndrome： a double blind randomized controlled trial

This study aimed to investigate the effect of intramuscular injection of testosterone undecanoate on overall quality of life （QoL） in men with testosterone deficiency syndrome （TDS）. A randomized controlled trial over a 12-month period was carried out in 2009. One hundred and twenty men aged 40 years and above with a diagnosis of TDS （serum total testosterone 〈12 nmol 1-1 and total Aging Male Symptom （AMS） scores ≥ 27） were invited to participate. Interventions comprised intramuscular injection of either placebo or 1000 mg testosterone undecanoate, given at weeks O, 6, 18, 30 and 42. This paper presents the secondary analysis of QoL changes measured in the scores of Short-Form-12 （SF-12） scale at baseline, weeks 30 and 48 after the first injection. A total of 56/60 and 58/60 men from the active treatment and placebo group, respectively, completed the study. At week 48, before adjusting for baseline differences, the QoL of men in the treatment group improved significantly in five out of the eight domains on SF-12. The physical health composite scores improved 4.0 points from a baseline of 41.9±7.0 in the treatment group compared to 0.8 point from a baseline of 43.7--7.1 in the placebo group （F=3.652, P=0.027）. The mental health composite scores improved 4.4 points from a baseline of 37.1±9.0 in the treatment group compared to 1.0 points from a baseline of 37.6±7.9 in the placebo group （F=4.514, P=-0.018）. After adjusting for baseline differences, significant improvement was observed in mental health composite scores, but not in physical health composite scores. LQng-acting testosterone undecanoate significanUy improved the mental health component of QoL in men with TDS.

Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly studied.METHODS This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MRI).RESULTS Of 88 patients enrolled in the index study,39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo.All patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD.Median liver fat at baseline was 15.0%(IQR 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo group.Median ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo group.At week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQR 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%P<0.001).After controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,P<0.001).CONCLUSION Testosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone.Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.

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

<abstract> 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.

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.

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.

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.

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.

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.

Protective mechanism of testosterone on cognitive impairment in a rat model of Alzheimer's disease

Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although the underlying protective mechanism of testosterone on cognitive performance remains unclear. This study explored the protective mechanism of a subcutaneous injection of 0.75 mg testosterone on cognitive dysfunction induced by bilateral injections of amyloid beta 1–42 oligomers into the lateral ventricles of male rats. Morris water maze test results demonstrated that testosterone treatment remarkably reduced escape latency and path length in Alzheimer's disease rat models. During probe trials, testosterone administration significantly elevated the percentage of time spent in the target quadrant and the number of platform crossings. However, flutamide, an androgen receptor antagonist, inhibited the protective effect of testosterone on cognitive performance in Alzheimer's disease rat models. Nissl staining, immunohistochemistry, western blot assay, and enzyme-linked immunosorbent assay results showed that the number of intact hippocampal pyramidal cells, the dendritic spine density in the hippocampal CA1 region, the immune response and expression level of postsynaptic density protein 95 in the hippocampus, and the activities of superoxide dismutase and glutathione peroxidase were increased with testosterone treatment. In contrast, testosterone treatment reduced malondialdehyde levels. Flutamide inhibited the effects of testosterone on all of these indicators. Our data showed that the protective effect of testosterone on cognitive dysfunction in Alzheimer's disease is mediated via androgen receptors to scavenge free radicals, thereby enhancing synaptic plasticity.

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.

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.

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.

Hormonal replacement therapy and aging: Asian practical recommendations on testosterone supplementation

<abstract>Profound and diffuse alterations in the production of gonadal and adrenal androgens as well as growth hormone are associated with aging. To convey this concept more appropriately, partial endocrine deficiency in the aging male (PEDAM) was introduced as a term for the phenomenon of hormonal alterations in the aging male. Hormones responsible for some of the manifestations associated with male aging are testosterone, growth hormone, dehydroepiansdrosterone (DHEA), melatonin, thyroid hormones and leptin. Of these, testosterone has been widely investigated and its beneficial and adverse effects on male bodily systems are relatively well established. However, a serious body of confusion and misunderstandings surrounding the diagnosis, treatment and monitoring of men suspected of having androgen deficiency has been raised. Therefore, it is timely to provide practical criteria for diagnosis and treatment to avoid misconception about the use of testosterone in the aging male. To provide an understanding and information of the issues, the following headings are summarized: (1) Important clinical consideration on testosterone supplementation in the aging male; (2) Asian practical recommendations on testosterone supplementation in the aging male.