Showing papers by "Christina Wang published in 2011"

Low Testosterone Associated With Obesity and the Metabolic Syndrome Contributes to Sexual Dysfunction and Cardiovascular Disease Risk in Men With Type 2 Diabetes

Abstract: Men with obesity, the metabolic syndrome, and type 2 diabetes have low total and free testosterone and low sex hormone–binding globulin (SHBG). Conversely, the presence of low testosterone and/or SHBG predicts the development of metabolic syndrome and type 2 diabetes. Visceral adiposity present in men with low testosterone, the metabolic syndrome, and/or type 2 diabetes acts through proinflammatory factors. These inflammatory markers contribute to vascular endothelial dysfunction with adverse sequelae such as increased cardiovascular disease (CVD) risk and erectile dysfunction. This review focuses on the multidirectional impact of low testosterone associated with obesity and the metabolic syndrome and its effects on erectile dysfunction and CVD risk in men with type 2 diabetes. Whenever possible in this review, we will cite recent reports (after 2005) and meta-analyses. ### Epidemiological studies of low testosterone, obesity, metabolic status, and erectile dysfunction Epidemiological studies support a bidirectional relationship between serum testosterone and obesity as well as between testosterone and the metabolic syndrome. Low serum total testosterone predicts the development of central obesity and accumulation of intra-abdominal fat (1–3). Also, low total and free testosterone and SHBG levels are associated with an increased risk of developing the metabolic syndrome, independent of age and obesity (1–3). Lowering serum T levels in older men with prostate cancer treated with androgen deprivation therapy increases body fat mass (4). Conversely, high BMI, central adiposity, and the metabolic syndrome are associated with and predict low serum total and to a lesser extent free testosterone and SHBG levels (1–3,5). Because obesity suppresses SHBG and as a result total testosterone concentrations, alterations in SHBG confound the relationship between testosterone and obesity. Low total testosterone or SHBG levels are associated with type 2 diabetes, independent of age, race, obesity, and criteria for diagnosis of diabetes (6,7). In longitudinal studies, low serum total and free testosterone …

Associations between urinary metabolites of di(2-ethylhexyl) phthalate and reproductive hormones in fertile men

Abstract: Widely used man-made chemicals, including phthalates, can induce hormonal alterations through a variety of cellular and molecular mechanisms. A number of rodent and observational studies have consistently demonstrated the anti-androgenic effect of several phthalates. However, there are only limited data on the relationship between exposure to these chemicals and reproductive hormone levels in men. All men (n = 425) were partners of pregnant women who participated in the Study for Future Families in five US cities and provided urine and serum samples on the same day. Eleven phthalate metabolites were measured in urine and serum samples were analysed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone, testosterone, inhibin B and oestradiol and sex hormone-binding globulin (SHBG). Pearson correlations and parametric tests were used for unadjusted analyses, and multiple linear regression analysis was performed controlling for appropriate covariates. We observed weak or no associations with urinary phthalates other than di(2-ethylhexyl) phthalate (DEHP). All measures of testosterone [total, calculated free testosterone and the free androgen index (FAI)] were inversely correlated with the urinary concentrations of four DEHP metabolites. After adjustment by appropriate covariates, there was no longer an association between urinary DEHP metabolite concentrations and total testosterone levels; however, FAI was significantly associated with the urinary concentrations of several DEHP metabolites. SHBG was positively related to the urinary concentrations of mono(2-ethylhexyl) phthalate, but not with other DEHP metabolites, an association that was attenuated after adjustment. Our results suggest that DEHP exposure of fertile men is associated with minor alterations of markers of free testosterone.

Efficacy and safety of the 2% formulation of testosterone topical solution applied to the axillae in androgen-deficient men

Abstract: Objectives Testosterone replacement therapy in hypogonadal men relieves symptoms and restores serum testosterone levels to the physiological range. In this study, we assessed the safety, pharmacokinetics, and efficacy of the 2% formulation of testosterone topical solution applied daily to the axillae. Design and patients An open-label trial was conducted in testosterone-deficient men who started on a daily dose of 60 mg of testosterone. Dose was adjusted on Days 45 and 90 when necessary to maintain serum testosterone levels within the physiological range (10·41-36·44 nmol/l) based on average serum testosterone levels on Days 15 and 60, respectively. Sexual function and mood changes were assessed by the Psychosexual Daily Questionnaire (PDQ) for the 7 days preceding visits at Days 1, 15, 60, and 120; and quality of life by SF-36 questionnaire on Days 1, 60, and 120. Safety parameters, laboratory tests, and adverse events were collected at each visit. Results Among the Completer Set (135 study completers and 3 patients who discontinued due to adverse events), 76·1% (Days 15/16), 84·8% (Days 60/61), and 84·1% (Days 120/121) had an average total testosterone level between 10·41-36·44 nmol/l. PDQ scores increased significantly from baseline to 120 days of treatment (p 2% of the 155 subjects who received ≥ 1 dose were application site irritation (7·1%), application site erythema (5·2%), headache (5·2%), increased hematocrit (3.9%), nasopharyngitis (3·9%), diarrhea (2·6%), and vomiting (2·6%). Conclusions These results indicate that once-daily application of the testosterone topical solution 2% to the axillae is a safe and effective treatment for androgen replacement in hypogonadal men.

Does ethnicity matter in male hormonal contraceptive efficacy

Abstract: The development of male hormonal contraception has progressed significantly during the last three decades. The ultimate goal is to produce an effective, safe and reversible male method of contraception that are within reach of and can be used by all men globally. This review aims to outline the recent developments in male hormonal contraception with special emphasis on how ethnicity influences acceptability, extent of sperm suppression, and rate of recovery of spermatogenesis. Baseline differences in testicular histomorphology and testosterone metabolism between East Asian and Caucasian men have been reported, but whether this contributes significantly to varying degrees of sperm suppression in response to exogenous testosterone therapy is less known. Testosterone alone male hormonal contraceptive regimens are effective and applicable for East Asian men, and less so for Caucasians. Combinations of progestins with androgens are sufficient to optimize effectiveness of suppression and applicability to all ethnicities. New compounds such as steroidal or non-steroidal selective androgen receptor modulators with dual androgenic and progestational activities are potential compounds for further development as male hormonal contraceptive methods. At the present time, combined androgen and progestin contraceptive regimens appear to be effective, safe, reversible and convenient to use for all men with ethnic, cultural and environmental differences. Further refinements on the hormonal agent, methods of delivery, and dose optimization of the androgen relative to the progestin are necessary. This goal mandates further investment and large clinical trials in multiethnic populations to better define safety and efficacy.

Mouse model for men with klinefelter syndrome: a multifaceted fit for a complex disorder

Abstract: 41 XXY mouse models share many characteristics of the human 47XXY Klinefelter syndrome (KS). This manuscript discusses the relative role of androgen deficiency and X chromosome genes resulting in the XXY mouse phenotype. The similarities in phenotype between 47XXY men and 41XXY mice suggest that the clinical manifestations in XXY men may be because of gene-dosage effect from genes that escape X inactivation in mouse. Conclusion: The 41XXY mouse is an excellent model for KS.

Testosterone Treatment of Older Men—Why Are Controversies Created?

Abstract: Cunningham and Toma have published an article entitled “Why Is Androgen Replacement in Males Controversial?” (1) in this issue of JCEM. This represents a new look at an old controversy. The article reviews the status of testosterone treatment in older men and serves as an extension to previously published guidelines on hypogonadism by Bhasin et al. (2) and recommendations published by Wang et al. (3) on late-onset hypogonadism. There are many causes for controversy in the practice of medicine, not the least of which is insufficiency of high-grade, evidence-based data. This is likely to occur when a medication was established in clinical use before the modern era of pharmaceutical regulation. This new review describes the insufficiency of evidence-based data to be certain that the benefit-to-risk ratio justifies testosterone treatment in older men, whereas taking the position that androgen replacement therapy in younger and middle-aged men is well established. The authors do acknowledge, as do the above guidelines (2), that relatively few large-scale, double-blind, placebo-controlled, multiple end point studies had been performed on testosterone treatment in men of any age. This position was also taken by the Institute of Medicine (4). Most of the data come from relatively small-size studies and meta-analyses of small- or medium-size databases (5,6,7,8).

Male hormonal contraception: Potential risks and benefits

Abstract: An effective, safe, reversible, and acceptable method of contraception is an important component of reproductive health and provides the opportunity of shared responsibility for family planning for both partners. Female hormonal contraceptives have been proven to be safe, reversible, available and widely acceptable by different populations. In contrast, male hormonal contraception, despite significant progress showing contraceptive efficacy comparable to female hormonal methods during last three decades, has not yet led to an approved product. Safety of a pharmaceutical product is an appropriate concern but the majority of male hormonal contraceptive clinical trials have not reported significant short term safety concerns. While the absence of serious adverse effects is encouraging, the studies have been designed for efficacy endpoints not long term safety. In this review we summarize potential risks and benefits of putative male hormonal contraceptives on reproductive and non-reproductive organs. While the review covers what we believe will be the likely class of drugs used for male hormonal contraception a true assessment of long term risks and benefits cannot be achieved without an available product.

Steady-state pharmacokinetics of oral testosterone undecanoate with concomitant inhibition of 5α-reductase by finasteride

Abstract: Oral testosterone undecanoate (TU) is used to treat testosterone deficiency; however, oral TU treatment elevates dihydrotestosterone (DHT), which may be associated with an increased risk of acne, male pattern baldness and prostate hyperplasia. Co-administration of 5α-reductase inhibitors with other formulations of oral testosterone suppresses DHT production and increases serum testosterone. We hypothesized that finasteride would increase serum testosterone and lower DHT during treatment with oral TU. Therefore, we studied the steady-state pharmacokinetics of oral TU, 200 mg equivalents of testosterone twice daily for 7 days, alone and with finasteride 0.5 and 1.0 mg po twice daily in an open-label, three-way crossover study in 11 young men with experimentally induced hypogonadism. On the seventh day of each dosing period, serum testosterone, DHT and oestradiol were measured at baseline and 1, 2, 4, 8, 12, 13, 14, 16, 20 and 24 h after the morning dose. Serum testosterone and DHT were significantly increased into and above their normal ranges similarly by all three treatments. Co-administration of finasteride at 0.5 and 1.0 mg po twice daily had no significant effect on either serum testosterone or DHT. Oral TU differs from other formulations of oral testosterone in its response to concomitant inhibition of 5α-reductase, perhaps because of its unique lymphatic route of absorption.

Association of testosterone level with phenotypic characteristics and long-term outcomes of men with COPD in the ECLIPSE cohort

Abstract: The impact of plasma total testosterone (T) level, measured by liquid chromatography tandem mass spectrometry, was evaluated in 1296 male COPD patients from the “Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints” (ECLIPSE) study in which GOLD II-IV COPD patients were followed without additional intervention for three years. Median T level was 439 ng/dL. T level was not correlated with% pred FEV 1 but was inversely correlated with body mass index (BMI) (Spearman9s r=-0.47) and positively correlated with% predicted total lung capacity (r=0.21), each p 1 , BMI, smoking status and T level, both COPD hospitalization and subject death were predicted by age and% predicted FEV 1 but T level was not predictive of COPD hospitalization and was only predictive of higher subject death in stage II patients (OR 0.25 p=0.007). In a large cohort of men with COPD, T level correlated with several COPD phenotypic characteristics. Low T tended to predict higher death rate particularly in subjects with moderate disease. The ECLIPSE Study was funded by GlaxoSmithKline (SCO104960, NCT00292552)