Displaying all 11 publications

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  1. Ho CC, Tong SF, Low WY, Ng CJ, Khoo EM, Lee VK, et al.
    BJU Int, 2012 Jul;110(2):260-5.
    PMID: 22093057 DOI: 10.1111/j.1464-410X.2011.10755.x
    Study Type - Therapy (RCT). Level of Evidence 1b. What's known on the subject? and What does the study add? Testosterone deficiency syndrome can be treated with testosterone replacement in the form of injectable, transdermal, buccal and oral preparations. Long-acting i.m. testosterone undecanoate 1000 mg, which is given at 10-14 week intervals, has been shown to be adequate for sustaining normal testosterone levels in hypogonadal men. This study confirms that long-acting i.m. testosterone undecanoate is effective in improving the health-related quality of life in men with testosterone deficiency syndrome as assessed by the improvement in the Aging Male Symptoms scale. Testosterone treatment can be indicated in men who have poor health-related quality of life resulting from testosterone deficiency syndrome.
    Matched MeSH terms: Testosterone/administration & dosage
  2. Chik Z, Johnston A, Tucker AT, Kirby K, Alam CA
    Int J Clin Pharmacol Ther, 2009 Apr;47(4):262-8.
    PMID: 19356392
    Circulating concentrations of endogenous compounds such as testosterone, complicate the analysis of pharmacokinetic parameters when these compounds are administered exogenously. This study examines the influence of three correction methods of accounting for endogenous concentrations on the determination of bioequivalence between two testosterone formulations.
    Matched MeSH terms: Testosterone/administration & dosage
  3. Yip CH, Pathmanathan R
    Singapore Med J, 1996 Feb;37(1):117-8.
    PMID: 8783930
    A case report of a male true hermaphrodite with 46XX/46XY karyotype is presented. He was first diagnosed at the age of 9 years when he presented with hypospadias and a left undescended testis. He was lost to follow-up until he presented at the age of 23 years with bilateral gynaecomastia. A hormonal profile showed a low testosterone level, while a seminal assay showed very few sperms. However he claimed to be sexually active. A year later, after he got married, he began to complain of impotence. A review of the condition is presented.
    Matched MeSH terms: Testosterone/administration & dosage
  4. 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/administration & dosage*
  5. Mohamad NV, Ima-Nirwana S, Chin KY
    Curr Drug Targets, 2018;19(8):898-906.
    PMID: 28914204 DOI: 10.2174/1389450118666170913162739
    Cognitive function and testosterone level of men decline concurrently with age. Low testosterone levels are associated with higher risk of Alzheimer's disease and mild cognitive impairment in men. There are continuous debates on whether this relationship is casual. This paper aims to summarize the current evidence on the association between testosterone level and cognitive function in elderly men. The presence of testosterone, androgen receptor and its responsive genes indicates that testosterone has biological functions in the central nervous system. The ability of the body to convert testosterone into estrogen suggests that part of the actions of testosterone could be mediated by estrogen. Observational studies generally showed that low endogenous testosterone levels were associated with poor cognitive performance in healthy elderly men. Testosterone substitution exerted positive effects on certain cognitive domains in normal and hypogonadal elderly men. In conclusion, testosterone may influence cognitive function in elderly men and its substitution may be considered in men with cognitive impairment and testosterone deficiency.
    Matched MeSH terms: Testosterone/administration & dosage*
  6. George A, Henkel R
    Andrologia, 2014 Sep;46(7):708-21.
    PMID: 24386995 DOI: 10.1111/and.12214
    The testosterone deficiency syndrome (TDS) is characterised by numerous symptoms, including low libido, increased fat mass, fatigue, erectile dysfunction or osteoporosis, and up to 80% of men will experience some kind of ageing males' symptoms. This is caused by the age-depending decline in serum testosterone levels with concentrations being about 40-50% lower in men older than 60 years compared with young men. This significant decline in testosterone levels is further closely linked with medical conditions such as obesity, metabolic syndrome, diabetes or hypertension. The conventional way of treating TDS is the testosterone replacement therapy (TRT), for which preparations are on the market. Apart from the beneficial effects of TRT, significant adverse side effects have been described, and prostate cancer (PCa) as absolute contraindication is debated. Eurycoma longifolia (Tongkat Ali; TA) is natural alternative to TRT and has been shown to restore serum testosterone levels, thus significantly improving sexual health. This includes significant positive effects on bone health and physical condition of patients. In addition, a significant antihyperglycaemic effect and cytotoxicity against PCas cells has been shown. Thus far, at therapeutic concentrations, no significant side effects of the treatment were obvious. Therefore, TA might be a safe alternative to TRT.
    Matched MeSH terms: Testosterone/administration & dosage*
  7. Loh SY, Giribabu N, Salleh N
    Exp Biol Med (Maywood), 2017 07;242(13):1376-1386.
    PMID: 28399644 DOI: 10.1177/1535370217703360
    We tested the hypothesis that testosterone-induced increase in blood pressure was due to changes in aquaporin (AQP) expression in kidneys. In this study, expression level of kidney AQPs was investigated under testosterone influence. Adult normotensive Wistar Kyoto (WKY) and hypertensive SHR male and female rats underwent gonadectomy. For female rats, testosterone was given for six weeks duration, two weeks following ovariectomy via subcutaneous silastic implant. Mean arterial pressure (MAP) was measured in all the rats after eight weeks via carotid artery cannulation and the rats were then sacrificed and kidneys were harvested for analyses of AQP-1, 2, 3, 4, 6, and 7 mRNA and protein expressions by quantitative real-time PCR and Western blotting, respectively. Distribution of AQP subunits' protein in kidneys was observed by immunofluorescence. In male WKY rats, MAP, AQP-1, 2, 4, and 7 protein; and mRNA expression decreased however AQP-3 protein and mRNA expression increased following orchidectomy. The vice versa effects were observed in testosterone-treated ovariectomized female WKY rats. However, no changes in AQP-6 expression were observed. Meanwhile, in adult male SHR rats, MAP and expression level of all AQP subunits decreased following orchidectomy. The opposite effects were seen in ovariectomized female SHR rats following testosterone treatment. Immunofluorescence study showed AQP-1 and AQP-7 were distributed in the proximal convoluted tubules (PCT) while AQP-2, AQP-4, and AQP-6 were distributed in the collecting ducts (CDs). AQP-3 was distributed in the PCT and CD. In conclusion, changes in AQP subunit expression in kidneys could explain changes in blood pressure under testosterone influence. Impact statement This study provides fundamental understanding on the mechanisms underlying testosterone-induced increase in blood pressure which involve regulation of aquaporin channel subunits in the kidneys. A better understanding of this issue can help to explain the reason for higher blood pressure in males as compared to females and may explain the reason for higher blood pressure in females after menopause than females before menopause, the former most probably related to the changes in female androgen.
    Matched MeSH terms: Testosterone/administration & dosage*
  8. Gholami K, Loh SY, Salleh N, Lam SK, Hoe SZ
    PLoS One, 2017;12(6):e0176368.
    PMID: 28591185 DOI: 10.1371/journal.pone.0176368
    Real-time quantitative PCR (qPCR) is the most reliable and accurate technique for analyses of gene expression. Endogenous reference genes are being used to normalize qPCR data even though their expression may vary under different conditions and in different tissues. Nonetheless, verification of expression of reference genes in selected studied tissue is essential in order to accurately assess the level of expression of target genes of interest. Therefore, in this study, we attempted to examine six commonly used reference genes in order to identify the gene being expressed most constantly under the influence of testosterone in the kidneys and hypothalamus. The reference genes include glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin beta (ACTB), beta-2 microglobulin (B2m), hypoxanthine phosphoribosyltransferase 1 (HPRT), peptidylprolylisomerase A (Ppia) and hydroxymethylbilane synthase (Hmbs). The cycle threshold (Ct) value for each gene was determined and data obtained were analyzed using the software programs NormFinder, geNorm, BestKeeper, and rank aggregation. Results showed that Hmbs and Ppia genes were the most stably expressed in the hypothalamus. Meanwhile, in kidneys, Hmbs and GAPDH appeared to be the most constant genes. In conclusion, variations in expression levels of reference genes occur in kidneys and hypothalamus under similar conditions; thus, it is important to verify reference gene levels in these tissues prior to commencing any studies.
    Matched MeSH terms: Testosterone/administration & dosage
  9. Loh SY, Giribabu N, Salleh N
    Steroids, 2017 Dec;128:128-135.
    PMID: 28954214 DOI: 10.1016/j.steroids.2017.09.008
    We hypothesized that testosterone-induced increase in blood pressure involve changes in aldosterone levels and expression of epithelial sodium channel (ENaC) in the kidneys.

    METHODS: Ovariectomized female normotensive Wistar Kyoto (WKY) and Spontaneous hypertensive (SHR) rats were given six weeks treatment with testosterone via subcutaneous silastic implant. The rats were anesthetized and mean arterial pressure (MAP) was measured via direct cannulation of the carotid artery. Animals were sacrificed and kidneys were removed and subjected for α, β and γ-ENaC protein and mRNA expression analyses by Western blotting and Real-time polymerase chain reaction (qPCR), respectively. Distributions of α, β and γ-ENaC proteins in kidneys were observed by immunofluorescence. Plasma testosterone, aldosterone, electrolytes, osmolality, urea and creatinine levels were determined by biochemical assays. Analysis were also performed in non-testosterone treated orchidectomized and sham-operated male WKY and SHR rats.

    RESULTS: Treatment of ovariectomized female WKY and SHR rats with testosterone causes increased in MAP but decreased in plasma aldosterone, sodium (Na+), osmolality and expression and distribution of α, β and γ-ENaC subunits in the kidneys. Orchidectomy decreased the MAP but increased plasma aldosterone, Na+, osmolality and α, β and γ-ENaC expression and distribution in the kidneys of male WKY and SHR rats.

    CONCLUSIONS: Decreased in plasma aldosterone, Na+ and ENaC levels in kidneys under testosterone influence indicated that testosterone-induced increased in MAP were not due to increased plasma aldosterone and ENaC levels in kidneys, and thus the testosterone effect on MAP likely involve other mechanisms.

    Matched MeSH terms: Testosterone/administration & dosage
  10. Dehghan F, Muniandy S, Yusof A, Salleh N
    Int J Med Sci, 2014;11(2):180-91.
    PMID: 24465164 DOI: 10.7150/ijms.6283
    The incidence of non-contact knee injury was found higher in female than in male and is related to the phases of the menstrual cycle. This raised the possibility that female sex-steroids are involved in the mechanism underlying this injury via affecting the expression of the receptors for relaxin, a peptide hormone known to modulate ligament laxity. Therefore, this study aims to investigate the effect of sex-steroids on relaxin receptor isoforms (RXFP1 & RXFP2) expression in the ligaments and tendons of the knee.

    METHODS: Ovariectomized adult female WKY rats were treated with different doses of estrogen (0.2, 2, 20 μg/kg), progesterone (4mg) and testosterone (125 & 250μg/kg) for three consecutive days. At the end of the treatment, the animals were sacrificed and the patellar tendon and lateral collateral ligament were harvested for mRNA and protein expression analyses by Real Time PCR and Western blotting respectively.

    RESULTS: RXFP1, the main isoform expressed in these knee structures and RXFP2 showed a dose-dependent increase in expression with estrogen. Progesterone treatment resulted in an increase while testosterone caused a dose-dependent decrease in the mRNA and protein expression of both relaxin receptor isoforms.

    DISCUSSION: Progesterone and high dose estrogen up-regulate while testosterone down-regulates RXFP1 and RXFP2 expression in the patellar tendon and lateral collateral ligament of rat's knee.

    CONCLUSION: Relaxin receptor isoforms up-regulation by progesterone and high dose estrogen could provide the basis for the reported increase in knee laxity while down-regulation of these receptor isoforms by testosterone could explain low incidence of non-contact knee injury in male.

    Matched MeSH terms: Testosterone/administration & dosage
  11. Chin KY, Gengatharan D, Mohd Nasru FS, Khairussam RA, Ern SL, Aminuddin SA, et al.
    Nutrients, 2016 Dec 14;8(12).
    PMID: 27983628
    Osteoporosis reduces the skeletal strength and increases the risk for fracture. It is an underdiagnosed disease in men. Annatto tocotrienol has been shown to improve bone structural indices and increase expression of bone formation genes in orchidectomized rats. This study aimed to evaluate the effects of annatto tocotrienol on biomechanical strength and calcium content of the bone in orchidectomized rats. Thirty three-month-old male Sprague-Dawley rats were randomly assigned to five groups. The baseline control (BC) group was sacrificed at the onset of the study. The sham-operated group (SHAM) received olive oil (the vehicle of tocotrienol) orally daily and peanut oil (the vehicle of testosterone) intramuscularly weekly. The remaining rats were orchidectomized and treated with three different regimens, i.e., (1) daily oral olive oil plus weekly intramuscular peanut oil injection; (2) daily oral annatto tocotrienol at 60 mg/kg plus weekly intramuscular peanut oil injection; (3) daily oral olive oil plus weekly intramuscular testosterone enanthate injection at 7 mg/kg. Blood, femur and tibia of the rats were harvested at the end of the two-month treatment period for the evaluation of serum total calcium and inorganic phosphate levels, bone biomechanical strength test and bone calcium content. Annatto-tocotrienol treatment improved serum calcium level and tibial calcium content (p < 0.05) but it did not affect femoral biomechanical strength (p > 0.05). In conclusion, annatto-tocotrienol at 60 mg/kg augments bone calcium level by preventing calcium mobilization into the circulation. A longer treatment period is needed for annatto tocotrienol to exert its effects on bone strength.
    Matched MeSH terms: Testosterone/administration & dosage
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