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Adrian S Dobs

Publications and source records attributed to Adrian S Dobs.

33 records · Page 2Linked to original sources
PubMed2004

New testosterone buccal system (Striant) delivers physiological testosterone levels: pharmacokinetics study in hypogonadal men.

A new mucoadhesive testosterone buccal system (Striant), 30 mg testosterone (T), was applied twice daily in 82 hypogonadal men for 3 months. Serum T, free T, and 5alpha-dihydrotestosterone were measured during this period. T pharmacokinetics were determined from the data obtained during a 24-h sampling at wk 12. Physiological mean serum T concentrations were steady and consistently maintained. The mean percentage of time over a 24-h period that total serum T concentrations were above the lower limit of adult male range was 80.1%. During treatment, mean serum 5alpha-dihydrotestosterone, free T, and estradiol concentrations paralleled serum T. T pharmacokinetics were not significantly affected by body mass index, age, food or beverage, gum abnormalities, or medications known to cause dry mouth. Gum-related adverse events occurred in 16.3% of subjects. Except for three subjects, the gum adverse effects occurred early during treatment, did not cause interruption of treatment, and resolved rapidly and completely. The T buccal system is a novel T formulation that offers a safe, effective, and convenient alternative to existing formulations for physiological T replacement therapy in hypogonadal men.

Adult↗
PubMed2004

Safety and adverse effects of androgens: how to counsel patients.

Recently, interest has grown in the use of androgen replacement therapy for postmenopausal women. Androgen replacement in women improves libido, bone density, and body composition. The adverse effects, like hirsutism, are generally mild, and the safety profile of transdermal testosterone replacement is more favorable than that of other modes of androgen therapy. Further studies may help to determine the effect of lipid changes on cardiac outcomes. We believe that long-term studies are necessary to observe the potential effect of androgen replacement on cardiovascular mortality, breast and endometrial tissues, and mood and anger before this therapy can be used routinely in women.

Acne Vulgaris↗
PubMed2003

Effects of simvastatin, an HMG-CoA reductase inhibitor, in patients with hypertriglyceridemia.

BACKGROUND: Patients with elevated levels of serum triglycerides (TG) often have other associated lipid abnormalities (e.g., low levels of high-density lipoprotein cholesterol [HDL-C]) and are at increased risk of developing coronary heart disease. Although the therapeutic benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in hypercholesterolemic patients have been well established, less is known about the effects of statins in patient populations with hypertriglyceridemia. HYPOTHESIS: The purpose of this study was to evaluate the lipoprotein-altering efficacy of simvastatin in hypertriglyceridemic patients. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. In all, 195 patients with fasting serum triglyceride levels between 300 and 900 mg/dl received once daily doses of placebo or simvastatin 20, 40, or 80 mg for 6 weeks. RESULTS: Compared with placebo, simvastatin treatment across all doses resulted in significant reductions (p < 0.05 - < 0.001) in serum levels of triglycerides (-20 to -31% decrease) and TG-rich lipoprotein particles. Significant (p < 0.001) reductions were also seen in low-density lipoprotein cholesterol (-25 to -35%) and non-HDL-C (-26 to -40%). Levels of HDL-C were increased (7-11%) in the simvastatin groups compared with placebo (p < 0.05 - < 0.001). CONCLUSION: The results of this study demonstrate the beneficial effects of simvastatin in patients with hypertriglyceridemia.

Adult↗
PubMed2003

Opiate drug use: a potential contributor to the endocrine and metabolic complications in human immunodeficiency virus disease.

Endocrine and metabolic abnormalities are common in human immunodeficiency virus (HIV) disease and have been attributed to both the disease and its treatment. Other risk factors and behaviors may also be important. Approximately 28% of new HIV infections occur in users of injection drugs, such as opiates. We focus on the effects of opiates on multiple endocrine systems and their potential to contribute to the metabolic and endocrine problems in HIV. Opiate use has been associated with hypogonadism, adrenal dysfunction, reduced bone mineral density, and growth-hormone abnormalities. In addition, some studies have suggested abnormalities in glucose and lipid metabolism among opiate users. Although much of the evidence should be viewed as preliminary, these potential abnormalities should be kept in mind when treating opiate-dependent patients infected with HIV.

Body Composition↗
PubMed2003

Fish oil supplementation in the treatment of cachexia in pancreatic cancer patients.

Patients with pancreatic cancer often experience a loss of weight and appetite, known as the anorexia-cachexia syndrome, which is associated with decreased quality of life and reduced survival. Research into the biological mechanisms of cachexia has demonstrated that an array of inflammatory mediators and tumor-derived factors cause appetite suppression, skeletal muscle proteolysis, and lipolysis,producing an overall hypercatabolic state that contributes to loss of fat and lean body mass. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to modulate levels of proinflammatory cytokines, hepatic acute phase proteins, eicosanoids, and tumor-derived factors in animal models of cancer and may reverse some aspects of the process of cachexia. Results of clinical trials of n-3 PUFAs in the form of fish oils have been mixed, but should encourage further investigation into dietary fish oil supplementation, including the most effective route of administration and the proper dosage to promote optimal weight maintenance and to limit side effects. Concerns about standardization and quality control should also be considered. With the current available evidence, a recommendation for the use of omega 3 polyunsaturated fatty acids in pancreatic cancer cachexia is premature.

Appetite↗
PubMed2003

New modalities of transdermal testosterone replacement.

Hypogonadism, irrespective of its etiology, has a negative impact on various physiologic parameters. These parameters may improve with testosterone replacement therapy. Before 1990, intramuscular testosterone esters were the principal modality of testosterone replacement in men with hypogonadism. Although effective, they have a non-physiologic pharmacokinetic profile. Recently, transdermal preparations of testosterone have become widely available. These include a scrotal patch, non-scrotal patches and, the most recent development, a gel. Several studies have shown that transdermal testosterone replacement is physiologic, efficacious and has a good safety profile. Transdermal testosterone replacement improves bone mass and lean body mass, decreases fat mass, and improves mood and sexual function. There are no harmful effects on the prostate and lipids. Acne, polycythemia, and gynecomastia are less common with this form of therapy than with the intramuscular esters.

Administration, Cutaneous↗
PubMed2002

Changes in the incidence and predictors of wasting syndrome related to human immunodeficiency virus infection, 1987-1999.

The authors examined the impact of potent antiretroviral therapy (ART) on the diagnosis of wasting syndrome in the Multicenter AIDS Cohort Study. Study time was divided into the periods 1988-1990, 1991-1993, 1994-1995, and 1996-1999 to correspond to different treatment eras. The proportion of acquired immunodeficiency syndrome diagnoses in which wasting was present increased from 5% in 1988-1990 to 7.1% in 1991-1993, 7.7% in 1994-1995, and 18.9% in 1996-1999. The incidence of wasting per 1,000 person-years increased from 7.5 in 1988-1990 to 14.4 in 1991-1993 and 22.1 in 1994-1995; it decreased to 13.4 in 1996-1999. Fewer patients with wasting had low hemoglobin and hematocrit levels and reported oral thrush in 1996-1999 than in any other period. Analysis of change in body mass index (weight (kg)/height (m)(2)) after wasting showed a faster return to prewasting levels in 1994-1995 and 1996-1999 than in earlier periods. Case-control analysis showed that wasting prior to 1996 was weakly associated with fatigue (p = 0.10), low hemoglobin (p = 0.11), and CD4-positive T-lymphocyte count (p = 0.04). During 1996-1999, wasting was weakly associated with diarrhea (p = 0.05) and potent ART (p = 0.097). Predictors of wasting have changed with potent ART. Further research is needed to determine whether lipodystrophy may be misdiagnosed as wasting syndrome.

Anemia↗
PubMed2002

Endocrine effects of marijuana.

In the 35 years since the active compound of marijuana, delta9-tetrahydrocannabinol, was isolated, the psychological and physiological impact of marijuana use has been actively investigated. Animal models have demonstrated that cannabinoid administration acutely alters multiple hormonal systems, including the suppression of the gonadal steroids, growth hormone, prolactin, and thyroid hormone and the activation of the hypothalamic-pituitary-adrenal axis. These effects are mediated by binding to the endogenous cannabinoid receptor in or near the hypothalamus. Despite these findings in animals, the effects in humans have been inconsistent, and discrepancies are likely due in part to the development of tolerance. The long-term consequences of marijuana use in humans on endocrine systems remain unclear.

Animals↗
PubMed2002

Long-term effects of androgen deprivation therapy in prostate cancer patients.

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers in men and has an increasing incidence. In 1999, 37 000 men died from PCa in the USA. Androgen deprivation therapy (ADT) with GnRH agonists is frequently employed in the treatment of recurrent and metastatic PCa by inducing medical castration, rendering these men hypogonadal. Because hypogonadism in men is associated with a wide range of complications, we attempted to determine the effects of long-term ADT in men with PCa. METHODS: We conducted a cross-sectional study at a tertiary care centre to determine the effect of ADT on lean body mass (LBM), muscle strength, bone mineral density (BMD), sexual function, and quality of life (QOL) in men with PCa. Three groups of men were enrolled: (1) 20 men with PCa who were undergoing medical castration with GnRH agonists for at least 12 months prior to the onset of the study (ADT group); (2) 18 age-matched men with nonmetastatic PCa who were post prostatectomy and/or radiotherapy but had not yet undergone ADT (non-ADT group); and (3) 20 age-matched normal men who were healthy and ambulatory (control group). RESULTS: Men on ADT had castrate levels of serum total testosterone (P < 0.0001), free testosterone (P < 0.0001) and oestradiol (P < 0.0001), which were significantly lower than in the other groups. Total body (P = 0.03) and lumbar spine (P < 0.0001) BMD was significantly lower in patients on ADT compared to other groups and was associated with higher levels of urinary N-telopeptide (P = 0.02). The ADT group had higher fat mass compared to the other groups (P = 0.0001) and significantly reduced upper body strength (P = 0.001) when compared to non-ADT patients. The ADT group had lower overall scores on Watt's Sexual Function Questionnaire compared to other groups (P = 0.0001), in particular a decrease in desire, arousal and frequency of spontaneous early morning erections. The ADT group also had lower overall QOL scores, resulting in significant limitation of physical function (P = 0.001), role limitation (P = 0.02) and perception of physical health (P = 0.004). CONCLUSIONS: This study suggests that osteoporosis, unfavourable body composition, sexual dysfunction and reduced quality of life are seen in patients receiving androgen deprivation therapy for at least 12 months. Longitudinal studies in this patient population will shed further light on the timing of the development and the extent of these complications. Meanwhile, this information will assist both physicians and patients with prostate cancer to make informed decisions regarding androgen deprivation therapy.

Aged↗
PubMed2002

Effect of methyl testosterone administration on plasma viscosity in postmenopausal women.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of mortality in women, with an incidence that increases after menopause, hence suggesting a cardioprotective role of oestrogen. Menopause also results in a decline in androgen levels with resulting symptoms of decreased libido and sexual dysfunction. Recently, there has been a growing interest in the treatment of postmenopausal women with androgens. However, no data are available on plasma viscosity and fibrinogen levels in postmenopausal women on combined oestrogen/androgen therapy. METHODS: We conducted a randomized, double-blind, parallel-group 16-week study evaluating the effects of methyltestosterone supplementation on plasma viscosity and fibrinogen levels in postmenopausal women already on oestrogen replacement therapy (ERT) for at least 3 months. Women 21 years and older who were menopausal (natural or surgical) for at least 12 months were enrolled in the study. Participants were randomized to (1) an oestrogen-only group taking 1.25 mg esterified oestrogen (E-group) and (2) an oestrogen plus methyltestosterone (1.25 mg esterified oestrogen and 2.5 mg methyltestosterone) group (EA-group). Progesterone was not administered during the study period and women with intact uteri were given medroxyprogesterone 10 mg daily for 14 days at the completion of the study. RESULTS: After 16 weeks of treatment, both groups had a significant increase in serum oestradiol levels from baseline. The levels of total oestrogen were significantly higher in the E-group compared to the EA-group (P < 0.001). There was a greater decrease in the LH and SHBG levels in the EA-group (P = 0.01). There was no difference in total testosterone; however, free testosterone levels were significantly higher in the EA-group (P = 0.01). At the end of the study, there was a significant decrease in plasma viscosity only in the EA-group (P = 0.01). Fibrinogen levels increased in both the groups, reaching significance only in the EA-group (P = 0.006). Baseline weight, body mass index (BMI) and the duration of menopausal status did not have any significant impact on the changes in plasma viscosity or fibrinogen. Women in the EA-group showed significant reductions in total cholesterol (P = 0.009), high density lipoprotein (HDL) (P < 0.001) and triglyceride (TG) levels (P = 0.001). There was no significant change in these parameters in the E-group. CONCLUSION: This prospective study shows that the treatment of postmenopausal women on oestrogen with low-dose oral methyltestosterone results in a significant reduction in plasma viscosity. This lowering of plasma viscosity was achieved despite an increase in fibrinogen levels. Significant lowering of lipoproteins, especially TG levels, might have been responsible for this benefit. The combination regimen did not result in major side-effects. Based on these results, we feel confident in recommending low-dose androgens to postmenopausal women with a history of sexual dysfunction and decreased libido.

Aged↗
PubMed2002

Evaluation of high-dose estrogen and high-dose estrogen plus methyltestosterone treatment on cognitive task performance in postmenopausal women.

OBJECTIVES: To investigate the cognitive effects of high-dose oral estrogen alone or in combination with oral methyltestosterone in postmenopausal women. METHODS: Participants were tested with a randomized, double-blind design on the Identical Pictures, Cube Comparisons, Building Memory and Shape Memory tasks before and after 4 months of hormone treatment. RESULTS: Women receiving estrogen and methyltestosterone maintained a steady level of performance on the Building Memory task, whereas those receiving estrogen alone showed a decrease in performance. CONCLUSIONS: These results indicate that the addition of testosterone to high-dose estrogen replacement exerts a protective effect on memory performance in postmenopausal women.

Aged↗
PubMed2002

Differential effects of oral estrogen versus oral estrogen-androgen replacement therapy on body composition in postmenopausal women.

Menopause is associated with decreased lean body mass and increased fat due to aging and declining hormone secretion. Estrogens or estrogen-progestins have been used to alleviate vasomotor symptoms. However, estrogen-androgen (E/A) therapy is also used for vasomotor symptom relief and has been shown to increase lean body mass while decreasing fat mass. The objective of this 16-wk, double-blind, randomized, parallel group clinical trial was to compare esterified estrogen plus methyltestosterone (1.25 mg estrogen + 2.5 mg methyltestosterone/d; E/A group) vs. esterified estrogen alone (1.25 mg/d; E group) on body composition. Forty postmenopausal women (mean age, 57 yr) participated. Compared with estrogen treatment alone, women in the E/A group increased their total lean body mass and reduced their percentage fat for all body parts (P < 0.05). After E/A treatment, there were statistically significant increases in lean body mass by 1.232 kg [0.181 +/- 0.004, 0.81 +/- 0.057, and 0.24 +/- 0.009 kg in the upper body (P = 0.021), trunk (P = 0.001), and lower body (P = 0.047), respectively]. In the E group, the increase was 0.31 +/- 0.004, 0.021 +/- 0.03, and 0.056 +/- 0.05 kg in the upper body, trunk, and lower body, respectively. In the E/A group, body fat was reduced by 0.90 kg (P = 0.18 for the trunk only), and percentage body fat declined by 7.4% (P < or = 0.05 for all body parts). Lower body strength increased by 23.1 kg (51 lb) in the E/A group vs. only 11 kg (24.25 lb) in the E group (P = 0.002 between groups). A statistically significant increase in weight (2.7 +/- 5.1 vs. 0.1 +/- 4.6 lb; P < 0.05) was observed in the E/A group compared with the E group. When subjects were given self-reporting questionnaires, more improvement was noted in sexual functioning and quality of life in the E/A group when compared with patients receiving E alone. There were no noteworthy side effects. In conclusion, E/A replacement therapy can improve body composition, lower-body muscle strength, quality of life, and sexual functioning in postmenopausal women.

Administration, Oral↗
PubMedDate not supplied

Klinefelter syndrome: expanding the phenotype and identifying new research directions.

PURPOSE: The purpose of this study is to summarize new data on etiology and clinical features of Klinefelter syndrome in order to derive research priorities. METHODS: This study was conducted using critical reviews of selective topics, emphasizing less well-recognized clinical findings. RESULTS AND CONCLUSIONS: The phenotype of the prototypic 47,XXY case is well recognized: seminiferous tubule dysgenesis and androgen deficiency. Less well appreciated is the varied expressivity of 47,XXY Klinefelter syndrome, in particular neurological/cognitive perturbations like language and behavioral problems. Effective therapies are available. Reproductive technologies allow 47,XXY men to sire offspring through intracytoplasmic sperm injection (ICSI); however, genetic counseling is complex and success is low. Behavioral and expressive language difficulties are amenable to treatment by androgen therapy and psychological help. Early treatment may be imperative for optimal outcome.

Biomedical Research↗