Serum Bioavailable Testosterone Levels Research Articles

Bioavailable Testosterone Predicts a Lower Risk of Alzheimer's Disease in Older Men

There is a paucity of data on the relationship between testosterone and Alzheimer's disease (AD) in older men. The objective of the present study was to investigate the effects of serum total testosterone (TT), bioavailable testosterone (BT), and sex hormone binding globulin (SHBG) levels on the subsequent risk of AD in nondemented Chinese older men. This was a one-year prospective cohort study. 153 ambulatory community-living nondemented Chinese older men, aged 55 years or over, were recruited and followed for one year. Morning serum TT, BT, and SHBG levels were measured at baseline. At one-year of followup, assessment for dementia and AD were performed. AD was diagnosed by the NINCDS-ADRDA criteria for probable AD. Overall, the mean age of the subjects was 72.7 (SD 6.9). 6.5% (n = 10) developed dementia (converters), all having AD. 93.5% (n = 143) did not develop dementia (non-converters). Logistic regression analysis for independent predictors of AD showed that the baseline serum BT level, systolic blood pressure (SBP) and ApoE "4 genotype were significant independent predictors, after adjustment for age, education, BMI, fasting plasma glucose, and serum HDLC levels. The baseline serum BT level predicted a reduced risk of AD (adjusted relative risk (RR) 0.22, 95% CI: 0.07-0.69)). Baseline SBP and ApoE "4 genotype but not SHBG were independent risk factors, with RRs of 1.04 and 5.04 respectively. In conclusion, the serum level of bioavailable testosterone in late life predicts a lower risk of future AD development in older men.

Validation of an Arabic ADAM questionnaire for androgen deficiency screening in the Arab community

Background. It is well documented that testosterone levels decline with age, this decline is associated with symptoms which could be assessed denoting androgen deficiency. We investigated the validity of an Arabic version of the Saint Louis University androgen deficiency in ageing men (ADAM) questionnaire to screen for androgen deficiency in Saudi and non Saudi Arabic speaking men.Methods. It was a cross sectional study of ambulatory community-based Arabic Saudi men recruited from Volunteers in Riyadh city, Capital of Saudi Arabia, aged 18–80 years. Seven hundred thirty men agreed to fill the Arabic ADAM questionnaire, they were invited to a morning blood sample for total testosterone and sex hormone binding globulin and those who agreed to complete the whole study were only 407 men. Low serum bioavailable testosterone (BT) levels (androgen deficiency) were defined as <10th percentile of serum BT levels in young healthy Saudi men (18–30 years).Results. Cronbach's Alpha of 0.71 (n = 730) showed a good internal consistency of the Arabic ADAM questionnaire. Among participants, 18.2% and 77.6% had low serum BT levels and a positive ADAM questionnaire, respectively. The prevalence of positive ADAM and low serum BT is increasing with age. The Arabic ADAM questionnaire had a high sensitivity of 86.5%, a low specificity of 24.3%, and positive predictive values (+PVs) and negative (−PVs) of 20.3% and 89%, respectively.Conclusion. The Arabic ADAM questionnaire has a very good sensitivity but very low specificity for screening of androgen deficiency in Saudi men, therefore biological confirmation is needed especially when clinical symptoms of androgen deficiency are present.

Serum Total and Bioavailable Testosterone Levels, Central Obesity, and Muscle Strength Changes with Aging in Healthy Chinese Men

To investigate the effects of the changes in serum bioavailable and total testosterone (TT) levels with aging on visceral body fat distribution and muscle strength in Chinese men. Cross-sectional study. Ambulatory care. Four hundred seventy-five healthy ambulatory Chinese men (aged 18-89, body mass index (BMI) 16.4-40.0 kg/m(2)). Morning serum total and bioavailable testosterone levels, waist circumference (WC), waist-hip ratio (WHR), and right handgrip strength. Mean serum TT levels fell mildly but significantly with aging (P=.02, linear trend; one-way analysis of variance (ANOVA)), whereas mean serum bioavailable testosterone (BT) levels fell greatly with aging (P<.001, linear trend, one-way ANOVA). The rates of decline in serum TT and BT levels were 0.2% and 1.14% per year, respectively. [Correction added after online publication 14-May-2008: BT levels have been corrected from 1.44% to 1.14%.] After adjustment for adiposity according to BMI, multiple linear regression analyses showed that age remained significantly related to serum TT and BT levels. Handgrip strength decreased with age (correlation coefficient (r)=-0.394, P<.001) and was greater with higher serum BT levels (r=0.239, P<.001) but not with higher TT levels. WHR, before and after adjustment for BMI, was inversely related to serum TT (r=-0.34 and -0.197 respectively, P<.001) and BT levels (r=-0.104, P<.05 and -0.161, P<.001, respectively). In Chinese men, serum BT levels decreased with aging and may contribute to central obesity and poorer muscle strength in aging men.

A Short Version of the ADAM Questionnaire for Androgen Deficiency in Chinese Men

A 10-question screening questionnaire for androgen deficiency in aging men (ADAM) was reported in previous white but not Chinese populations. We therefore investigated the validity of a Chinese version of the Saint Louis University ADAM questionnaire to screen for androgen deficiency in Chinese men. This was a cross-sectional study. Seven hundred ninety-six ambulatory community-based Chinese men, 18-89 years old, were recruited from October 2003 through June 2006. Self-administered Chinese ADAM questionnaire and morning blood samples for serum total testosterone (TT) and bioavailable testosterone (BT) levels were collected from all participants. Low serum BT levels (androgen deficiency) were defined as <5th percentile of serum BT levels in young healthy Chinese men (18-29 years). The Chinese ADAM questionnaire had good internal consistency (Cronbach alpha = 0.74) and test-retest reliability (Pearson correlation coefficient, r = 0.86; p <.001, two-tailed). As a screening test for low serum BT levels, the Chinese ADAM questionnaire has a high sensitivity of 88% but low specificity of 32%. In 6 of the 10 questions, the mean serum BT levels were significantly lower in those who answered positively than in those who answered negatively. Using a cut-off score of > or =2, a six-question short Chinese ADAM questionnaire demonstrated sensitivity, specificity, and positive and negative predictive values of 86%, 40%, 46%, and 82%, respectively. We have validated a full Chinese version and developed a shortened version of the ADAM questionnaire, and demonstrated that they are sensitive but not specific screening tests for androgen deficiency in Chinese men.

P-156: Low serum bioavailable testosterone levels are associated with mild cognitive impairment in Chinese older men

P-156: Low serum bioavailable testosterone levels are associated with mild cognitive impairment in Chinese older men

Sexual Dysfunction in Women With Polycystic Ovary Syndrome: The Effects of Testosterone, Obesity, and Depression

In Brief Objectives: We examine the relationship among sexual function, obesity, psychologic depression, and serum total (totT) and bioavailable (bioT) testosterone levels in a group of premenopausal women with polycystic ovary syndrome (PCOS). Methods: Women with PCOS were given the Female Sexual Function Index (FSFI), the Sexual Distress Scale, the Sexual Energy Scale, the Beck Depression Inventory, a Perceived Body Image Questionnaire, and a bioT and totT blood test. Two-tailed Pearson correlations were made between sexual function, body mass index, depression, and T levels. Results: Thirty-three women (mean age 36) completed the questionnaires, and 23 underwent bioT and totT levels. Twenty-one of 33 (64%) women reported sexually related personal distress, and 20/33 (61%) reported some degree of depression. Sexual distress and depression were each associated with lack of sexual desire, arousal, lubrication, and orgasm (P < 0.05). All women were either overweight or clinically obese. Negative self-image was associated with a higher totT, a higher body mass index, depression, sexual distress, and lack of arousal and lubrication (P < 0.05). BioT level correlated positively with sexual desire (r = 0.46, P = 0.03) and negatively with sexual distress (r = −0.49, P = 0.02). Conclusions: Our study population of women with PCOS demonstrated a high level of sexual dysfunction. All of these women were clinically obese, and negative body image was found to correlate with sexual dysfunction. The majority experienced psychologic depression, which also correlated with the degree of sexual dysfunction. Despite these variables, elevated serum bioavailable testosterone levels correlated positively with sexual desire. We used validated questionnaires to examine the relationship among sexual function, obesity, psychologic depression, and serum total and bioavailable testosterone levels in a group of premeno-pausal women with polycystic ovary syndrome. Elevated serum bioavailable testosterone levels correlated positively with sexual desire.

Differential Effects of Antiepileptic Drugs on Neuroactive Steroids in Men with Epilepsy

To compare serum levels of neuroactive steroids among men with epilepsy who take various antiepileptic drugs, untreated men with epilepsy and normal controls (NC). Subjects were 85 men with localization-related epilepsy [unmedicated >6 months (No Rx)-10, carbamazepine (CBZ)-25, phenytoin (PHT)-25, lamotrigine (LTG)-25] and 25 NC. Sexual function scores (S-Score), hormone levels [dehydroepiandrosterone sulfate (DHEAS), bioactive (BA) testosterone (T), estradiol (BAE), and androstanediol (BAL)] and the ratios of inhibitory to excitatory neuroactive metabolites of T, i.e., BAL/BAE, were compared among groups. S-scores, DHEAS, and bioactive testosterone (BAT) were significantly (p < 0.05) lower and BAL and BAL/BAE were significantly higher among CBZ and PHT groups than among NC and LTG groups. LTG did not differ from NC in any of these measures. BAT correlated significantly with BAL/BAE for PHT (r = 0.44, p = 0.02) and CBZ (r = 0.42, p = 0.03) but not for NC (r = 0.03, p = NS) and LTG (r = 0.06, p = NS) groups. In comparison to LTG, enzyme inducing AEDs (CBZ, PHT) are associated with a more favorable neuroactive steroid balance (lower DHEAS and higher BAL/BAE) for seizure management, but at the expense of reduced serum bioavailable testosterone levels and sexual function.

P1-186: Low serum bioavailable testosterone levels are associated with mild cognitive impairment and Alzheimer’s disease in Chinese older men

P1-186: Low serum bioavailable testosterone levels are associated with mild cognitive impairment and Alzheimer’s disease in Chinese older men

Transdermal testosterone in female cancer survivors with decreased libido

8507 Background: Problems with sexual functioning are an issue negatively affecting the quality of life of female cancer survivors. Testosterone has been implicated as an important hormone in sexual functioning such as libido. Studies of transdermal testosterone have shown benefit in enhancing libido in women who have been diagnosed with hypoactive sexual desire disorder after bilateral oophorectomy. This phase III placebo-controlled clinical trial evaluated whether transdermal testosterone would increase libido in female cancer survivors. Methods: Women with a history of cancer, currently without evidence of disease, were eligible if they reported a decrease in sexual desire and had a sexual partner. Women must have been postmenopausal. Eligible women were randomized to receive 2% testosterone in Vanicream (10 mg daily) versus placebo Vanicream for four weeks, then crossed over to the opposite treatment. The primary endpoint, libido, was measured via the desire subscales of the Changes in Sexual Functioning Questionnaire (CSFQ), which were completed at baseline and at the end of 4 and 8 weeks of treatment. The primary endpoint was the average intra-patient change from baseline to four weeks in the CSFQ subscales between the two arms. A total of 64 patients per group were needed to provide 80% power to detect a difference of 8 units between the treatment means. Two-sided alternative hypothesis testing and a 5% Type I error rate were used. Results: One hundred fifty women were enrolled onto this study. Complete data were available for 132 women. For those on active testosterone cream, serum bioavailable testosterone levels increased significantly over placebo, with a mean change from baseline of 12 and 10 ng/dl for the first and second period, respectively (p&lt;.0001). The average intra-patient change from baseline to week 4 in libido was 5.5 on testosterone and 4.4 on placebo (p=0.58). No carryover effect was detected. The difference in average intra-patient changes from baseline for the entire crossover design between the two arms was only 1.1 points (95% confidence interval of -1.2 to 3.4, p=0.35). Conclusion: Testosterone is not a panacea for libido troubles in women with a history of cancer. Further studies are needed to determine whether there is a role for transdermal testosterone in this population. No significant financial relationships to disclose.

Correlates of osteoprotegerin levels in women and men.

Osteoprotegerin (OPG) is a potent antiresorptive molecule that binds the final effector for osteoclastogenesis, receptor activator of NF-kappaB ligand (RANK-L). OPG production is regulated by a number of cytokines and hormones, including sex steroids, but there are few data on age and gender effects on circulating serum OPG levels, as well as possible relationships between OPG levels and bone turnover markers or bone mineral density (BMD). Thus, we measured serum OPG levels in an age-stratified, random sample of men (n = 346 age range, 23-90 years) and women (n = 304; age range 21-93 years) and related them to sex steroid levels, bone turnover markers and BMD. Serum OPG levels increased with age in both men (R = 0.39, p < 0.001) and women (R = 0.18, p < 0.01). Premenopausal women had higher OPG levels than men under age 50 years (171 +/- 6 pg/ml vs 134 +/- 6 pg/ml, respectively, p < 0.001), whereas serum OPG levels were no different in postmenopausal women compared with men = 50 years (195 +/- 7 pg/ml vs 188 +/- 7 pg/ml, respectively, p = 0.179). OPG levels correlated inversely with serum bioavailable testosterone levels in men = 50 years (R = -0.27, p < 0.001), but no associations were present with either estrogen or testosterone levels in the women. In the men, there was a trend for OPG levels to be associated positively with bone resorption markers and inversely with BMD. Collectively, the gender difference in OPG levels suggests that sex steroids may regulate OPG production in vivo, as has been found in vitro. Moreover, OPG production may also rise with increases in bone turnover, probably as a homeostatic mechanism to limit bone loss. Further studies directly testing these hypotheses should provide additional insights into the potential role of OPG in bone loss related to aging and sex steroid deficiency.

A common promotor variant in the cytochrome P450c17alpha (CYP17) gene is associated with bioavailability testosterone levels and bone size in men.

Cytochrome P450c17alpha (CYP17) encodes an enzyme with 17a-hydroxylase and 17,20-lyase activities, which is essential for the normal production of adrenal and gonadal androgens. Because androgens have powerful effects on bone growth and metabolism, we determined whether a single base pair (bp) substitution (T-->C) in the promoter region (-34 bp) of CYP17 is associated with sex hormone levels, stature, and femoral mass and size in 333 white men aged 51-84 years (mean +/- SD; 66+/-7 years). Femoral neck bone mineral content (BMC), cross-sectional area (CSA), and bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry (DXA). Genotype frequencies did not deviate from Hardy-Weinberg expectations. Serum bioavailable testosterone levels were 20% or 0.5 SDs higher in men with the C/C compared with the T/T genotype, whereas heterozygous men had intermediate hormone levels (p = 0.019). Men with the C/C genotype also were nearly 3 cm taller and had 0.6 SD greater femoral neck CSA than men with the T/T genotype (p < or = 0.01 for both). The association with CSA persisted after adjusting for age, height, and body weight. In contrast, CYP17 genotype was not associated with femoral neck BMC, areal BMD (g/cm2), or estimated volumetric BMD (g/cm3). These results suggest that allelic variation at the CYP17 locus may contribute to the genetic influence on stature and femoral size in men.

Hypothalamo—pituitary—gonadal function in aging men

Aging in healthy men is accompanied by a progressive decline of gonadal function with, in particular, a decline of Leydig cell function and decreased testosterone production. Population means for total serum testosterone decrease by about 30% between the ages of 25 and 75 years. Over the same period, mean serum levels of free or bioavailable testosterone decrease by as much as 50%. The decline of Leydig cell function in aging is the consequence of primary testicular changes, with decreased numbers of Leydig cells, and alterations in neuroendocrine regulation of the pituitary secretion of luteinizing hormone (LH), with an inappropriately low LH drive in the face of a persistent relative hypoandrogenism. The changes in neuroendocrine regulation of LH secretion are situated primarily at the hypothalamic level with, in particular, an increased sensitivity to the negative feedback effects of sex steroids. The testicular changes and the altered regulation of LH secretion are accompanied by an independent, age-associated increase of serum sex hormone binding globulin levels, which explains the steeper decline of serum bioavailable testosterone levels as compared to total serum testosterone levels. More limited information indicates that global Sertoli cell function and spermatogenesis are relatively well preserved in elderly men, although this appears to require increased follicle stimulating hormone (FSH) drive to compensate for primary testicular changes. Thus, whereas aging is accompanied by testicular changes affecting both Leydig cells and Sertoli cells, there appears to be a dissociation in neuroendocrine response with deficient LH secretion but appropriately increased FSH release.