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  1. 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/deficiency
  2. Fulltext A randomized, double-blind, placebo-controlled trial on the effect of long-acting testosterone treatment as assessed by the Aging Male Symptoms scale
    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/deficiency*
  3. Fulltext True hermaphrodite--a case report
    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/deficiency
  4. Fulltext Effect of long-acting testosterone undecanoate treatment on quality of life in men with testosterone deficiency syndrome: a double blind randomized controlled trial
    Tong SF, Ng CJ, Lee BC, Lee VK, Khoo EM, Lee EG, et al.
    Asian J Androl, 2012 Jul;14(4):604-11.
    PMID: 22635164 DOI: 10.1038/aja.2011.178
    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 l(-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 0, 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. Long-acting testosterone undecanoate significantly improved the mental health component of QoL in men with TDS.
    Matched MeSH terms: Testosterone/deficiency*
  5. Influence of testosterone on mean arterial pressure: A physiological study in male and female normotensive WKY and hypertensive SHR rats
    Loh SY, Salleh N
    Physiol Int, 2017 Mar 01;104(1):25-34.
    PMID: 28361574 DOI: 10.1556/2060.104.2017.1.3
    Introduction Testosterone plays an important role in the blood pressure regulation. However, information with regard to the effect of this hormone on blood pressure in normotensive and hypertensive conditions is limited. Therefore, in this study, the relationship between plasma testosterone level and mean arterial pressure (MAP) was investigated under these conditions. Methods Normotensive Wistar-Kyoto (WKY) and hypertensive Spontaneous Hypertensive (SHR) male and female rats were gonadectomized with female rats treated with testosterone. Estrous cycle stages of intact female rats of both strains were identified by vaginal smear. Pressure in the carotid artery of anesthetized rats was measured via direct cannulation technique. The blood was withdrawn for plasma testosterone level measurement by enzyme-linked immunosorbent assay. Results Treatment of ovariectomized female WKY and SHR rats with testosterone for 6-week duration has resulted in MAP to increase (P 
    Matched MeSH terms: Testosterone/deficiency
  6. A Review on the Effects of Testosterone Supplementation in Hypogonadal Men with Cognitive Impairment
    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/deficiency
  7. Fulltext Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies
    Watts EL, Appleby PN, Perez-Cornago A, Bueno-de-Mesquita HB, Chan JM, Chen C, et al.
    Eur Urol, 2018 Nov;74(5):585-594.
    PMID: 30077399 DOI: 10.1016/j.eururo.2018.07.024
    BACKGROUND: Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.

    OBJECTIVE: To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.

    DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.

    RESULTS AND LIMITATIONS: Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p<0.001) compared with men with higher concentrations (2nd-10th tenths of the distribution). Heterogeneity was present by tumour grade (phet=0.01), with a lower risk of low-grade disease (OR=0.76, 95% CI 0.67-0.88) and a nonsignificantly higher risk of high-grade disease (OR=1.56, 95% CI 0.95-2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation.

    CONCLUSIONS: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade.

    PATIENT SUMMARY: In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer.

    Matched MeSH terms: Testosterone/deficiency*
  8. Fulltext Annatto tocotrienol improves indices of bone static histomorphometry in osteoporosis due to testosterone deficiency in rats
    Chin KY, Abdul-Majeed S, Fozi NF, Ima-Nirwana S
    Nutrients, 2014 Nov;6(11):4974-83.
    PMID: 25389899 DOI: 10.3390/nu6114974
    This study aimed to evaluate the effects of annatto tocotrienol on indices of bone static histomorphometry in orchidectomized rats. Forty male rats were randomized into baseline (BL), sham (SH), orchidectomized (ORX), annatto tocotrienol-treated (AnTT) and testosterone enanthate-treated (TE) groups. The BL group was sacrificed upon receipt. All rats except the SH group underwent bilateral orchidectomy. Annatto tocotrienol at 60 mg/kg body weight was administered orally daily to the AnTT group for eight weeks. Testosterone enanthate at 7 mg/kg body weight was administered intramuscularly once weekly for eight weeks to the TE group. The rat femurs were collected for static histomorphometric analysis upon necropsy. The results indicated that the ORX group had significantly higher osteoclast surface and eroded surface, and significantly lower osteoblast surface, osteoid surface and osteoid volume compared to the SH group (p < 0.05). Annatto tocotrienol and testosterone enanthate intervention prevented all these changes (p < 0.05). The efficacy of annatto tocotrienol was on par with testosterone enanthate. In conclusion, annatto tocotrienol at 60 mg/kg can prevent the imbalance in bone remodeling caused by increased osteoclast and bone resorption, and decreased osteoblast and bone formation. This serves as a basis for the application of annatto tocotrienol in hypogonadal men as an antiosteoporotic agent.
    Matched MeSH terms: Testosterone/deficiency*
  9. 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/deficiency*
  10. The anti-osteoporotic effect of Eurycoma Longifolia in aged orchidectomised rat model
    Shuid AN, Abu Bakar MF, Abdul Shukor TA, Muhammad N, Mohamed N, Soelaiman IN
    Aging Male, 2011 Sep;14(3):150-4.
    PMID: 20874437 DOI: 10.3109/13685538.2010.511327
    Osteoporosis in elderly men is becoming an important health issue with the aging society. Elderly men with androgen deficiency are exposed to osteoporosis and can be treated with testosterone replacement. In this study, Eurycoma longifolia (EL), a plant with androgenic effects, was supplemented to an androgen-deficient osteoporotic aged rat as alternative to testosterone. Aged 12 months old Sprague-Dawley rats were divided into groups of normal control (NC), sham-operated (SO), orchidectomised-control (OrxC), orchidectomised and supplemented with EL (Orx + El) and orchidectomised and given testosterone (Orx + T). After 6 weeks of treatment, serum osteocalcin, serum terminal C-telopeptide Type 1 collagen (CTX) and the fourth lumbar bone calcium were measured. There were no significant differences in the osteocalcin levels before and after treatment in all the groups. The CTX levels were also similar for all the groups before treatment. However, after treatment, orchidectomy had caused significant elevation of CTX compared to normal control rats. Testosterone replacements in orchidectomised rats were able to prevent the rise of CTX. Orchidectomy had also reduced the bone calcium level compared to normal control rats. Both testosterone replacement and EL supplementation to orchidectomised rats were able to maintain the bone calcium level, with the former showing better effects. As a conclusion, EL prevented bone calcium loss in orchidectomised rats and therefore has the potential to be used as an alternative treatment for androgen deficient osteoporosis.
    Matched MeSH terms: Testosterone/deficiency
  11. Erectile dysfunction and comorbidities in aging men: an urban cross-sectional study in Malaysia
    Khoo EM, Tan HM, Low WY
    J Sex Med, 2008 Dec;5(12):2925-34.
    PMID: 18761590 DOI: 10.1111/j.1743-6109.2008.00988.x
    INTRODUCTION: Erectile dysfunction (ED), lower urinary tract symptoms (LUTS), cardiovascular disease (CVD), depression, and androgen deficiency are common conditions affecting aging men over 50 years. However, data were limited in developing countries.
    AIMS: To investigate the prevalence of ED, LUTS, chronic diseases, depression, androgen deficiency symptoms, and lifestyle of aging men in Malaysia, and to examine their associations with sociodemographic factors.
    MAIN OUTCOME MEASURES: ED, LUTS, chronic diseases, depression, positive Androgen Deficiency in the Aging Male (ADAM) questionnaire
    METHODS: A randomized survey of 351 men using structured questionnaires consisting of self-reported medical conditions, International Index for Erectile Function-5, International Prostate Symptom Score, Geriatric Depression Scale-15, and St Louis University questionnaire for ADAM. Blood samples were taken for glucose, lipid, prostate specific antigen (PSA), and hormones.
    RESULTS: Mean age was 58+/-7 years. Prevalence of ED was 70.1% (mild ED 32.8%, mild to moderate ED 17.7%, moderate ED 5.1%, and severe ED 14.5%). There were 29% of men with moderate and severe LUTS; 11.1% had severe depression; 25.4% scored positive on ADAM questionnaire; 30.2% self-reported hypertension, 21.4% self-reported diabetes mellitus; 10.8% self-reported coronary artery disease; 19.1% were smokers; and 34% consumed alcohol. There were 78.6% of men that are overweight and obese; 28.8% had a fasting blood sugar (FBS) >or=6.1 mmol/L, 70.1% had total cholesterol >5.2 mmol/L, 19.1% had total testosterone >or=11.0 nmoL/L, 14.0% had calculated free testosterone <0.0225 nmoL/dL; 4% had PSA >4 microg/L; 9.4% had insulin-like growth factor-1 (IGF-1) level below age specific range, 5.1% had abnormal sex hormone binding globulin (<15 nmoL/L and >70 nmol/L). ED was found to be significantly associated with LUTS, depression (P<0.001 respectively). Similarly, LUTS was significantly associated with depression and ADAM questionnaire status (P<0.001 respectively); and ADAM questionnaire status was also significantly associated with depression (P<0.001).
    CONCLUSION: ED, LUTS, depression, and androgen deficiency symptoms are common in urban aging men. As these conditions are possibly interrelated, strategies for early disease prevention and detection are warranted when one disease presents.
    Matched MeSH terms: Testosterone/deficiency
  12. Fulltext Establishing an Animal Model of Secondary Osteoporosis by Using a Gonadotropin-releasing Hormone Agonist
    Mohamad NV, Che Zulkepli MAA, May Theseira K, Zulkifli N, Shahrom NQ, Ridzuan NAM, et al.
    Int J Med Sci, 2018;15(4):300-308.
    PMID: 29511366 DOI: 10.7150/ijms.22732
    Introduction: Orchidectomy is currently the preferred method to induce bone loss in preclinical male osteoporosis model. Gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer treatment can induce testosterone deficiency but its effects on bone in preclinical male osteoporosis model are less studied. Objective: This study aimed to evaluate the skeletal effect of buserelin (a GnRH agonist) in male rats and compare it with orchidectomy. Methods: Forty-six three-month-old male Sprague-Dawley rats were divided into three experimental arms. The baseline arm (n=6) was sacrificed at the onset of the study. In the buserelin arm, the rats received a daily subcutaneous injection of either normal saline (n=8), buserelin acetate at 25 µg/kg (n=8) or 75 µg/kg (n=8). In the orchidectomy arm, the rats were either sham-operated (n=8) or orchidectomized (n=8). All groups underwent in-vivo X-ray micro-computed tomography scanning at the left proximal tibia every month. Blood was collected at the beginning and the end of the study for testosterone level evaluation. The rats were euthanized after the three-month treatment. The femurs were harvested for biomechanical strength and bone calcium determination. Results: The results showed that buserelin at both doses caused a significant decline in testosterone level and deterioration in bone microstructure (p<0.05), but did not affect bone calcium content (p>0.05). Buserelin at 25 µg/kg decreased displacement and strain of the femur significantly (p<0.05). Similar changes were observed in the orchidectomized group compared to the sham-operated group but without any significant changes in biomechanical strength (p>0.05). Conclusion: Buserelin can induce testosterone deficiency and the associated deterioration of bone microarchitecture similar to orchidectomy in three months. However, it may require a longer time to show significant effects on bone strength and mineral content.
    Matched MeSH terms: Testosterone/deficiency
  13. The Effects of Annatto Tocotrienol on Bone Biomechanical Strength and Bone Calcium Content in an Animal Model of Osteoporosis Due to Testosterone Deficiency
    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/deficiency
  14. Efficacy and safety of long-acting intramuscular testosterone undecanoate in aging men: a randomised controlled study
    Tan WS, Low WY, Ng CJ, Tan WK, Tong SF, Ho C, et al.
    BJU Int, 2013 Jun;111(7):1130-40.
    PMID: 23651425 DOI: 10.1111/bju.12037
    OBJECTIVE: To evaluate the efficacy and safety of long-acting i.m. testosterone undecanoate (TU) in Malaysian men with testosterone deficiency (TD).

    PATIENTS AND METHODS: A total of 120 men, aged 40-70 years, with TD (serum total testosterone [TT] ≤ 12 nmol/L) were randomised to receive either i.m. TU (1000 mg) or placebo. In all, 58 and 56 men in the placebo and treatment arm, respectively, completed the study. Participants were seen six times in the 48-week period and the following data were collected: physical examination results, haemoglobin, haematocrit, TT, lipid profile, fasting blood glucose, sex hormone-binding globulin, liver function test, prostate- specific antigen (PSA) and adverse events.

    RESULTS: The mean (sd) age of the participants was 53.4 (7.6) years. A significant increase in serum TT (P < 0.001), PSA (P = 0.010), haematocrit (P < 0.001), haemoglobin (P < 0.001) and total bilirubin (P = 0.001) were seen in the treatment arm over the 48-week period. Two men in the placebo arm and one man in the treatment arm developed myocardial infarction. Common adverse events observed in the treatment arm included itching/swelling/pain at the site of injection, flushing and acne. Overall, TU injections were well tolerated.

    CONCLUSIONS: TU significantly increases serum testosterone in men with TD. PSA, haemoglobin and haematocrit were significantly elevated but were within clinically safe limits. There was no significant adverse reaction that led to the cessation of treatment.

    Matched MeSH terms: Testosterone/deficiency
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