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Standardised water-soluble extract of Eurycoma longifolia, Tongkat ali, as testosterone booster for managing men with late-onset hypogonadism?

Tambi MI, Imran MK, Henkel RR

Andrologia, 2012 May;44 Suppl 1:226-30.
PMID: 21671978 DOI: 10.1111/j.1439-0272.2011.01168.x

In most countries, millions of people are relying on herbal medicines as remedy for numerous ailments. In South-East Asia, Eurycoma longifolia Jack, also known as 'Malaysian ginseng' or Tongkat ali, is used to combat stress and disease and to improve physical strength. Moreover, the compounds of the roots of this plant are reported to have aphrodisiac and testosterone enhancing effects in the rat. Considering that human studies are not available, 76 of 320 patients suffering from late-onset hypogonadism (LOH) were given 200 mg of a standardised water-soluble extract of Tongkat ali for 1 month. The Ageing Males' Symptoms (AMS) according to the standardised rating scale and the serum testosterone concentration were taken. Results show that treatment of LOH patients with this Tongkat ali extract significantly (P < 0.0001) improved the AMS score as well as the serum testosterone concentration. While before treatment only 10.5% of the patients did not show any complaint according to the AMS scale and 35.5% had normal testosterone levels, after the completed treatment 71.7% and 90.8% of the patients showed normal values, respectively. Thus, Tongkat ali extract appears to be useful as a supplement in overcoming the symptoms of LOH and for the management of hypogonadism.

Matched MeSH terms: Testosterone/blood
Strain differences in intermale aggression and possible factors regulating increased aggression in Japanese quail

Maekawa F, Nagino K, Yang J, Htike NTT, Tsukahara S, Ubuka T, et al.

Gen Comp Endocrinol, 2018 01 15;256:63-70.
PMID: 28765073 DOI: 10.1016/j.ygcen.2017.07.025

The National Institute for Environmental Studies (NIES) of Japan established a strain of Japanese quail (Coturnix japonica) known as NIES-L by rotation breeding in a closed colony for over 35years; accordingly, the strain has highly inbred-like characteristics. Another strain called NIES-Brn has been maintained by randomized breeding in a closed colony to produce outbred-like characteristics. The current study aimed to characterize intermale aggressive behaviors in both strains and to identify possible factors regulating higher aggression in the hypothalamus, such as sex hormone and neuropeptide expression. Both strains displayed a common set of intermale aggressive behaviors that included pecking, grabbing, mounting, and cloacal contact behavior, although NIES-Brn quail showed significantly more grabbing, mounting, and cloacal contact behavior than did NIES-L quail. We examined sex hormone levels in the blood and diencephalon in both strains. Testosterone concentrations were significantly higher in the blood and diencephalon of NIES-Brn quail compared to NIES-L quail. We next examined gene expression in the hypothalamus of both strains using an Agilent gene expression microarray and real-time RT-PCR and found that gene expression of mesotocin (an oxytocin homologue) was significantly higher in the hypothalamus of NIES-Brn quail compared to NIES-L quail. Immunohistochemistry of the hypothalamus revealed that numbers of large cells (cell area>500μm2) expressing mesotocin were significantly higher in the NIES-Brn strain compared to the NIES-L strain. Taken together, our findings suggest that higher testosterone and mesotocin levels in the hypothalamus may be responsible for higher aggression in the NIES-Brn quail strain.

Matched MeSH terms: Testosterone/blood
Testosterone is associated with age-related changes in bone health status, muscle strength and body composition in men

Chin KY, Soelaiman IN, Naina Mohamed I, Shahar S, Teng NI, Suhana Mohd Ramli E, et al.

Aging Male, 2012 Dec;15(4):240-5.
PMID: 23098182 DOI: 10.3109/13685538.2012.724740

OBJECTIVE: Variations in testosterone levels are associated with several outcomes of aging. The present study aimed to examine the relationship between age-related decline of testosterone levels and changes in bone health status, handgrip strength, body fat percentage and fat-free mass.
MATERIALS AND METHODS: A total of 335 Malaysian Chinese and Malay men aged 40 years and above were recruited for this study. Their body compositions, calcaneal speed of sound and handgrip strength were measured and their blood was collected. Linear regression analysis was done to examine the relationship among age, testosterone levels and outcomes of aging.
RESULTS: The results indicated significant changes in all testosterone measurements, sex hormone binding globulin level, calcaneal speed of sound, handgrip strength, body fat percentage and fat-free mass with age (p < 0.05). Age-dependent decline in bioavailable and free testosterone levels were significantly associated with reduction in calcaneal speed of sound, fat-free mass and handgrip strength (p < 0.05). Age-dependent decline in the total testosterone level was significantly associated with an increase in body fat percentage among the elderly men (p < 0.05).
CONCLUSION: Testosterone levels are associated with changes in outcome of aging such as bone health status, muscle strength and body composition, and the relationships are age-dependent.

Matched MeSH terms: Testosterone/blood*
Testosterone up-regulates vacuolar ATPase expression and functional activities in vas deferens of orchidectomized rats

Khadijah Ramli NS, Giribabu N, Muniandy S, Salleh N

Theriogenology, 2018 Mar 01;108:354-361.
PMID: 29294437 DOI: 10.1016/j.theriogenology.2017.12.035

Precise regulation of vas deferens fluid pH is essential for sperm. However, the mechanisms underlying effect of testosterone on vas deferens fluid pH have never been identified, which could involve changes in expression and functional activity of vacoular (V)-ATPase.
METHODS: Orchidectomized, adult male Sprague-Dawley rats were treated subcutaneously with 125 μg/kg/day and 250 μg/kg/day testosterone with or without flutamide (androgen receptor blocker) and finasteride (5α-reductase inhibitor) for seven (7) days. Following treatment completion, in vivo perfusion of vas deferens lumen was performed and changes in fluid secretion rate, pH and HCO3- content were measured with and without bafilomycin, a V-ATPase inhibitor. Rats were then sacrificed and vas deferens were harvested and subjected for V-ATPase A1 and B1/2 protein expression and distribution analysis by western blotting and immunohistochemistry, respectively.
RESULTS: In sham-operated and testosterone-treated orchidectomized rats, higher fluid secretion rate, which was not antagonized by bafilomycin but lower HCO3- content and pH which were antagonized by bafilomycin were observed when compared to orchidectomized-only and orchidectomized, testosterone-treated rats receiving flutamide or finasteride, respectively. Bafilomycin had no effect on fluid secretion rate, HCO3- content and pH in orchidectomized and testosterone-treated orchidectomized rats receiving flutamide and finasteride. V-ATPase A1 and B1/2 proteins were expressed at high levels in vas deferens and were highly distributed at the apical membrane of luminal epithelium and in muscle layer of this organ, mainly in sham and testosterone-treated orchidectomized rats.
CONCLUSIONS: V-ATPase is involved in acidification of vas deferens fluid under testosterone influence.

Matched MeSH terms: Testosterone/blood
Testosterone, dehydroepiandrosterone and 4-androstene-3, 17-dione concentrations in maternal and fetal plasma in the last days of ovine gestation

Colás AE, Curet LB

Biol Reprod, 1978 Apr;18(3):434-40.
PMID: 149570
Matched MeSH terms: Testosterone/blood*
Fulltext The Effects of Quassinoid-Rich Eurycoma longifolia Extract on Bone Turnover and Histomorphometry Indices in the Androgen-Deficient Osteoporosis Rat Model

Jayusman PA, Mohamed IN, Alias E, Mohamed N, Shuid AN

Nutrients, 2018 Jun 21;10(7).
PMID: 29933617 DOI: 10.3390/nu10070799

Male osteoporosis is associated with higher rates of disability and mortality. Hence the search for suitable intervention and treatment to prevent the degeneration of skeletal health in men is necessary. Eurycoma longifolia (EL), a traditional plant with aphrodisiac potential may be used to treat and prevent male osteoporosis. The skeletal protective effect of quassinoid-rich EL extract, which has a high content of eurycomanone, has not been studied. This study aimed to determine whether EL could prevent skeletal deteriorations in gonadal hormone-deficient male rats. Ninety-six male Sprague⁻Dawley rats were randomly assigned to baseline, sham-operated (Sham), orchidectomised or chemically castrated groups. Chemical castration was achieved via subcutaneous injection of degarelix at 2 mg/kg. The orchidectomised and degarelix-castrated rats were then divided into negative control groups (ORX, DGX), testosterone-treated groups (intramuscular injection at 7 mg/kg weekly) (ORX + TES, DGX + TES), and EL-supplemented groups receiving daily oral gavages at doses of 25 mg/kg (ORX + EL25, DGX + EL25), 50 mg/kg (ORX + EL50, DGX + EL50), and 100 mg/kg (ORX + EL100, DGX + EL100). Following 10 weeks of treatment, the rats were euthanized and their blood and femora were collected. Bone biochemical markers, serum testosterone, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa β-ligand (RANKL) levels and histomorphometric indices were evaluated. Quassinoid-rich EL supplementation was found to reduce degenerative changes of trabecular structure by improving bone volume, trabecular number, and separation. A reduction in the percentage of osteoclast and increase in percentage of osteoblast on bone surface were also seen with EL supplementation. Dynamic histomorphometric analysis showed that the single-labeled surface was significantly decreased while the double-labeled surface was significantly increased with EL supplementations. There was a marginal but significant increase in serum testosterone levels in the ORX + EL25, DGX + EL50, and DGX + EL100 groups compared to their negative control groups. Quassinoid-rich EL extract was effective in reducing skeletal deteriorations in the androgen-deficient osteoporosis rat model.

Matched MeSH terms: Testosterone/blood
The effect of organochlorines and heavy metals on sex steroid-binding proteins in vitro in the plasma of nesting green turtles, Chelonia mydas

Ikonomopoulou MP, Olszowy H, Hodge M, Bradley AJ

J. Comp. Physiol. B, Biochem. Syst. Environ. Physiol., 2009 Jul;179(5):653-62.
PMID: 19247670 DOI: 10.1007/s00360-009-0347-3

In this study on green turtles, Chelonia mydas, from Peninsular Malaysia, the effect of selected environmental toxicants was examined in vitro. Emphasis was placed on purported hormone-mimicking chemicals such as dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene, dieldrin, lead, zinc and copper. Five concentrations were used: high (1 mg/L), medium (10(-1) mg/L), low (10(-2) mg/L), very low (10(-6) mg/L) and control (diluted carrier solvent but no toxicants). The results suggest that environmental pesticides and heavy metals may significantly alter the binding of steroids [i.e. testosterone (T) and oestradiol] to the plasma proteins in vitro. Competition studies showed that only Cu competed for binding sites with testosterone in the plasma collected from nesting C. mydas. Dieldrin and all heavy metals competed with oestradiol for binding sites. Furthermore, testosterone binding affinity was affected at various DDT concentrations and was hypothesised that DDT in vivo may act to inhibit steroid-protein interactions in nesting C. mydas. Although the precise molecular mechanism is yet to be described, DDT could have an effect upon the protein conformation thus affecting T binding (e.g. the T binding site on the steroid hormone binding protein molecule).

Matched MeSH terms: Testosterone/blood
Fulltext The effects of Tualang honey on female reproductive organs, tibia bone and hormonal profile in ovariectomised rats--animal model for menopause

Zaid SS, Sulaiman SA, Sirajudeen KN, Othman NH

BMC Complement Altern Med, 2010;10:82.
PMID: 21194469 DOI: 10.1186/1472-6882-10-82

Honey is a highly nutritional natural product that has been widely used in folk medicine for a number of therapeutic purposes. We evaluated whether Malaysian Tualang honey (AgroMas, Malaysia) was effective in reducing menopausal syndrome in ovariectomised female rats; an animal model for menopause.

Matched MeSH terms: Testosterone/blood
The effects of orchidectomy and supraphysiological testosterone administration on trabecular bone structure and gene expression in rats

Chin KY, Ima-Nirwana S

Aging Male, 2015 Mar;18(1):60-6.
PMID: 25166624 DOI: 10.3109/13685538.2014.954995

This study aimed to determine the effects of orchidectomy and supraphysiological testosterone replacement on trabecular structure and gene expression in the bone.

Matched MeSH terms: Testosterone/blood
The relationship between circulating testosterone and inflammatory cytokines in men

Mohamad NV, Wong SK, Wan Hasan WN, Jolly JJ, Nur-Farhana MF, Ima-Nirwana S, et al.

Aging Male, 2019 Jun;22(2):129-140.
PMID: 29925283 DOI: 10.1080/13685538.2018.1482487

Testosterone is the predominant gonadal androgen in men. Low testosterone levels are found to be associated with an increased in metabolic risk and systematic inflammation. Since adipose tissue is a source of inflammatory cytokines, testosterone may regulate inflammation by acting on adipose tissue. This review aimed to explore the role of testosterone in inflammation and its mechanism of action. Both animal studies and human studies showed that (1) testosterone deficiency was associated with an increase in pro-inflammatory cytokines; (2) testosterone substitution reduced pro-inflammatory cytokines. The suppression of inflammation by testosterone were observed in patients with coronary artery disease, prostate cancer and diabetes mellitus through the increase in anti-inflammatory cytokines (IL-10) and the decrease in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Despite these, some studies also reported a non-significant relationship. In conclusion, testosterone may possess anti-inflammatory properties but its magnitude is debatable. More evidence is needed to validate the use of testosterone as a marker and in the management of chronic inflammatory diseases.

Matched MeSH terms: Testosterone/blood*
The triad of erectile dysfunction, testosterone deficiency syndrome and metabolic syndrome: findings from a multi-ethnic Asian men study (The Subang Men's Health Study)

Tan WS, Ng CJ, Khoo EM, Low WY, Tan HM

Aging Male, 2011 Dec;14(4):231-6.
PMID: 22115177 DOI: 10.3109/13685538.2011.597463

The etiology of erectile dysfunction (ED) is multi-factorial. This paper examines the association between ED, testosterone deficiency syndrome (TDS) and metabolic syndrome (MS) in Malaysian men in an urban setting. One thousand and forty-six men aged ≥ 40 years from Subang Jaya, Malaysia were randomly selected from an electoral-roll list. The men completed questionnaires that included: socio-demographic data, self-reported medical problems and the International Index of erectile function (IIEF-5). Physical examination and the following biochemical tests were performed: lipid profile, fasting blood glucose (FBG) and total testosterone. The response rate was 62.8% and the mean age of men was 55.8 ± 8.4 (41-93) years. Ethnic distribution was Chinese, 48.9%; Malay, 34.5%; Indian, 14.8%. The prevalence of moderate-severe ED was 20.0%, while 16.1% of men had TDS (< 10.4 nmol/L) and 31.3% of men had MS. Indian and Malay men were significantly more likely to have ED (p = 0.001), TDS (p < 0.001) and MS (p < 0.001) than the Chinese. Multivariate regression analysis showed that elevated blood pressure, elevated FBG, low high-density lipoprotein and heart disease were predictors of ED while all MS components were independently associated with TDS. Malay and Indian men have a higher disease burden compared to Chinese men and were more likely to suffer with ED, TDS and MS. MS components were closely related to TDS and ED.

Matched MeSH terms: Testosterone/blood
Tocotrienol-rich fraction supplementation prevents foetal loss in females mated with corticosterone-treated male Sprague-Dawley rats

Abd Aziz NAA, Chatterjee A, Chatterjee R, Durairajanayagam D

Andrologia, 2019 Apr;51(3):e13199.
PMID: 30461035 DOI: 10.1111/and.13199

This study examined whether tocotrienol supplementation to corticosterone-treated male rats could prevent foetal loss in females upon their mating. Epididymides of adult male Sprague-Dawley (SD) rats with proven fertility were surgically separated at the testis-caput junction. Twenty-four hours post-surgery, these animals received for 7 days either: tocopherol-stripped corn oil (Control), corticosterone 25 mg/kg s.c. (CORT), CORT 25 mg/kg s.c. and tocotrienol-rich fraction (TRF) 100 mg/kg orally (CORT + TRF) or TRF 100 mg/kg orally (TRF). On day 8, males were cohabited with proestrus females. A spermatozoa-positive vaginal smear indicated pregnancy. Males were euthanised for analysis of testosterone and antioxidant activities. Reproductive organs were weighed. On day 8 of pregnancy, females were laparotomised to count the number of implantation sites. Pregnancy was continued until term. Number of pups delivered and their weights were determined. Data were analysed using ANOVA. Malondialdehyde levels were significantly lower in CORT + TRF group compared with CORT group. Enzymatic antioxidant activities, testosterone level and reproductive organ weights were significantly higher in CORT + TRF group compared with CORT group. Number of implantation sites and live pups delivered, and their birth weights from females mated with CORT + TRF males were significantly higher compared to CORT group. Therefore, TRF prevents foetal loss in females mated with CORT + TRF-treated males.

Matched MeSH terms: Testosterone/blood
Total testosterone and sex hormone-binding globulin are significantly associated with metabolic syndrome in middle-aged and elderly men

Chin KY, Ima-Nirwana S, Mohamed IN, Aminuddin A, Ngah WZ

Exp. Clin. Endocrinol. Diabetes, 2013 Jul;121(7):407-12.
PMID: 23765753 DOI: 10.1055/s-0033-1345164

Testosterone and sex hormone-binding globulin (SHBG) have been shown to be associated with metabolic syndrome (MS) in men. This study aimed at validating these relationships in a group of middle-aged and elderly men and assessing their strength of association to MS. A cross-sectional study of 332 Malaysian men aged 40 years and above was conducted. The blood of subject was collected under fasting condition for determination of testosterone, SHBG, glucose and lipid levels. Their medical history, smoking and alcohol consumption status, waist circumference (WC), body mass index (BMI) and blood pressure (BP) were recorded. All testosterone and SHBG levels were significantly reduced in MS subjects compared to non-MS subjects (p<0.05). Testosterone and SHBG were correlated significantly with most of the MS indicators without adjustments. In multiple regression analysis, the triglyceride level was the only MS indicator that was significantly, inversely and independently associated with all testosterone measurements and SHBG (p<0.05). Waist circumference was significantly and negatively associated with SHBG level (p<0.05) though not independent of BMI. Total testosterone and SHBG were significantly and inversely associated with the presence of MS. Testosterone and SHBG are potential intervention targets for the prevention of MS in men.

Matched MeSH terms: Testosterone/blood*
Fulltext Vascular Dysfunction among Malaysian Men with Increased BMI: An Indication of Synergistic Effect of Free Testosterone and Inflammation

Aminuddin A, Salamt N, Ahmad Fuad AF, Chin KY, Ugusman A, Soelaiman IN, et al.

Medicina (Kaunas), 2019 Sep 08;55(9).
PMID: 31500378 DOI: 10.3390/medicina55090575

Background and objectives: Obesity is associated with poor vascular function and may lead to future cardiovascular disease (CVD). Obesity is also related to increased inflammation and a low testosterone level. This study was conducted to determine the relationship between inflammation, testosterone level, and vascular function among subjects with an increased body mass index (BMI) and to determine whether both low testosterone and high inflammation have synergistic effects towards vascular dysfunction. Materials and Methods: A total of 303 men aged 40-80 years were recruited from Klang Valley, Malaysia. Their height, weight, blood pressure (BP), lipid, blood glucose level, total testosterone (TT), free testosterone (FT), and C-reactive protein (CRP) were measured. The carotid femoral pulse wave velocity (PWVCF) and augmentation index (AI) were also recorded as markers of vascular function. Results: The mean age of all the subjects was 54.46 ± 9.77 years. Subjects were divided into a low/normal body mass index (BMI) group (BMI < 25 kg/m2; NG, n = 154) and high BMI group (BMI ≥ 25 kg/m2; OG, n = 149). The mean BMI for NG was 22.20 ± 1.94 kg/m2 while for OG was 28.87 ± 3.24 kg/m2 (p < 0.01). The level of TT (OG = 21.13 ± 6.44 versus NG = 16.18 ± 6.16 nmol/L, p < 0.01) and FT (OG = 0.34 ± 0.12 versus NG = 0.39 ± 0.11 nmol/L, p < 0.01) were reduced while the level of CRP [OG = 1.05 (2.80) versus NG = 0.50 (1.50) mmol/L, p = 0.01] was increased in OG compared to NG. PWVCF (OG = 8.55 ± 1.34 versus NG = 8.52 ± 1.42 m/s, p = 0.02) and AI (OG = 16.91% ± 6.00% versus 15.88% ± 5.58%, p < 0.01) were significantly increased in OG after adjustment for other CVD risk factors. The subjects that had both a low FT and an increased CRP had higher AI when compared to those with a high CRP and high FT (p < 0.01). Conclusions: The increased BMI was associated with vascular dysfunction, mediated by a low testosterone level and increased inflammation. Furthermore, having both conditions concurrently lead to higher vascular dysfunction. Weight loss, testosterone supplementation, and the anti-inflammatory agent may be beneficial for men to prevent vascular dysfunction.

Matched MeSH terms: Testosterone/blood
Vitamin D is significantly associated with total testosterone and sex hormone-binding globulin in Malaysian men

Chin KY, Ima-Nirwana S, Wan Ngah WZ

Aging Male, 2015;18(3):175-9.
PMID: 26004987 DOI: 10.3109/13685538.2015.1034686

OBJECTIVE: Cross-sectional studies in the Caucasian population have shown a significant relationship between vitamin D and testosterone levels, but data in the Asian population are limited. This study aimed to determine the association between vitamin D and testosterone levels in Malaysian men.
METHODS: Chinese and Malay men (n = 382) aged 20 years or above residing in the Klang Valley, Malaysia were recruited. Their fasting blood was collected for serum testosterone, sex hormone-binding globulin (SHBG) and 25-hydroxyvitamin D (25(OH)D) assays. Relationship between 25(OH)D and testosterone levels was analyzed using multiple regression analysis. Testosterone and SHBG levels among subjects with different vitamin D status were compared using univariate analysis. Confounders such as age, ethnicity and body mass index (BMI) were adjusted.
RESULTS: 25(OH)D was significantly and positively associated with total testosterone and SHBG levels before and after adjustment for age and ethnicity (p 0.05).
CONCLUSION: 25(OH)D is significantly associated with total testosterone and SHBG in Malaysian men but this association is BMI-dependent.

Matched MeSH terms: Testosterone/blood*
Vitamin E attenuates nicotine- and noise-induced reproductive impairment in male albino Wistar rats

Bisong SA, Ukoh IE, Nna VU, Ebong PE

Andrologia, 2018 Sep;50(7):e13050.
PMID: 29806220 DOI: 10.1111/and.13050

Previous studies showed that exposure to stress or nicotine induced reproductive impairment in male rats. Here, we assessed the effect of an antioxidant (vitamin E) on nicotine-, stress- and nicotine + stress-induced reproductive impairment in male rats. Forty-eight male albino Wistar rats were divided into eight groups as follows; control, stress (generator noise 90-120 dB, 8 hr/day), nicotine (1.5 mg kg-1 day-1 ), nicotine + stress, vitamin E (100 mg kg-1 day-1 ), stress + vitamin E, nicotine + vitamin E and stress + nicotine + vitamin E. Sperm count, viability, motility and rapid progressive forward movement decreased significantly (p

Matched MeSH terms: Testosterone/blood

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