Testosterone and prostate health: debunking myths demands evidence, caution, and good clinical judgment.
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Biomedical subjects
Publications and source records attributed to Alvaro Morales.
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Dietary patterns reflect combinations of dietary exposures, and here we examine these in relation to prostate cancer risk. In a case-control study, 80 incident primary prostate cancer cases and 334 urology clinic controls were enrolled from 1997 through 1999 in Kingston, Ontario, Canada. Food-frequency questionnaires were completed prior to diagnosis and assessed intake in the 1-year period 2-3 years prior to enrollment. Among controls, dietary intake was used in principal components analyses to identify patterns that were then evaluated with all subjects in relation to prostate cancer risk using unconditional logistic regression, controlling for age. Four dietary patterns were identified: Healthy Living, Traditional Western, Processed and Beverages. Increased prostate cancer risk is apparent in relation to the Processed pattern, composed of processed meats, red meats, organ meats, refined grains, white bread, onions and tomatoes, vegetable oil and juice, soft drinks and bottled water. The OR for the highest tertile compared to baseline is 2.75 (95% CI 1.40-5.39), with a dose-response pattern (trend test p < 0.0035). Our results suggest that a dietary pattern including refined grain products, processed meats and red and organ meats contributes to increased prostate cancer risk. Since dietary information was collected before subjects knew their diagnosis, recall bias was avoided.
Here we describe the cytotoxic and proapoptotic effect of an ent-kaurane (ent-16beta-17alpha-dihydroxykaurane), compound isolated from Croton malambo barks, on malignant cell growth. When MCF-7 mammary carcinoma cells were treated with increasing concentrations of the ent-kauranoid, its cytotoxic activity showed an IC50 of 12.5microg/ml, dose that is 2.66-fold lower than the corresponding value for non-malignant cells. At this growth inhibitory dose, both mRNA and protein levels for Bcl-2 as well as mRNA for hTERT were significantly reduced. The observed preapoptotic activity seemed to be triggered by a mechanism that is not directly affecting NF-(kappa)B binding ability. The potential use of this plant-derived compound as a cancer chemotherapy agent is discussed.
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PURPOSE: We investigated the feasibility and safety of intraprostatic administration of bacillus Calmette-Guerin (BCG) and determined the histological changes induced by this approach. MATERIALS AND METHODS: A total of 36 healthy male beagle dogs 2.2 to 3.6 years old weighing 10.0 to 14.8 kg were randomly assigned to 6 experimental groups. Four groups were given intradermal BCG vaccination and 6 weeks later they were given 0 (group 1), 10 (group 2), 5 x 10 (group 3) or 10 (group 4) BCG organisms intraprostatically. An additional group received prevaccination, followed 6 weeks later by a dose of 10 BCG organisms intraprostatically and then 6 weeks of antibiotics (group 5). Another group receiving no prevaccination and 5 x 10 BCG organisms intraprostatically at week 6 were included (group 6). RESULTS: Adverse reactions (ARs) were seen in 12 dogs, including inguinal lymphadenopathy in 3, an anal lesion in 5, constipation in 7 and dysuria in 3. There was a trend toward an increased incidence of ARs in high dose groups 3 and 4, fewer ARs in group 5 and no ARs in group 6. There was minimal evidence of systemic dissemination of BCG in any group. Post-necropsy histological analysis indicated higher inflammation as well as glandular destruction in high dose groups 3 and 4. Antibiotics did not seem to lessen the histological response to intraprostatic BCG injection (group 5). Interestingly in nonvaccinated group 6 the level of inflammation as well as glandular destruction was higher. CONCLUSIONS: Our results indicate that intraprostatic BCG administration in dogs is a safe and well tolerated procedure. It is free of major or long lasting serious complications.
The issues surrounding androgen replacement therapy in men with symptomatic late-onset hypogonadism has been marred in controversy even before the identification and synthesis of testosterone. The controversy has attained renewed importance because of the ever increasing aging population. Physicians attuned with the various diagnostic approaches, familiar with the advantages and drawbacks of testosterone preparations, and aware of the potential safety issues are well positioned to deal with the hypogonadal man at or beyond middle age. The urologist is in a unique position to assist patients and colleagues in other specialties, particularly in relation to prostate safety. This update focuses on the most prominent areas of controversy.
OBJECTIVE: To assess whether testosterone (T) supplementation in men considered to have symptomatic late-onset hypogonadism (SLOH) can be evaluated clinically and biochemically. PATIENTS AND METHODS: To assess the relevance of the clinical and biochemical diagnosis of hypogonadism we investigated patients referred for the diagnosis and treatment of SLOH. Patients were assessed clinically and completed a screening questionnaire. The pituitary-adrenal-gonadal axis was comprehensively assessed biochemically. Those with a clinical diagnosis of hypogonadism and serum levels of T supporting such a diagnosis received exogenous T for >/= 3 months and were assessed for any clinical and biochemical response. Of an initial group of 45 men (mean age 59.2 years) 38 completed the study. RESULTS: Most men presented with symptoms of sexual dysfunction, lack of energy and/or depression. There were differences before and after treatment only in bioavailable T (BT), with none in the levels of total T (TT). There was a strong correlation before and after treatment in the levels of luteinizing hormone and follicle-stimulating hormone, and a weak negative correlation between gonadotrophins and BT. Neither TT nor BT had predictive value for the treatment response. There was a trend to a correlation between BT levels and treatment success. Changes in serum prostate specific antigen were insignificant during the limited period. CONCLUSION: The lack of accurate methods for diagnosing SLOH suggests that a therapeutic trial of T supplementation is warranted in men in whom there are no contraindications. The 3-month period largely circumvents the placebo effect and has minimal risks for serious adverse effects (mostly in relation to prostate safety). This controversial position needs further evaluation with a larger cohort and other biochemical measurements.
INTRODUCTION: There are few published guidelines for the management of sexual dysfunctions in men and women, despite the prevalence and lack of attention to these problems. Disorders of sexual function in men include erectile dysfunction, orgasm/ejaculation disorders, priapism, and Peyronie's disease. AIM: To provide evidence-based and expert-opinion consensus guidelines for the clinical management of men's sexual dysfunctions. METHODS: An International Consultation in collaboration with major urological and sexual medicine societies assembled over 200 multidisciplinary experts from 60 countries into 17 consultation committees. Committee members established the scope and objectives for each chapter. Following intensive review of available data and publications, committees developed evidence-based guidelines in each area. MAIN OUTCOME MEASURE: New algorithms and guidelines for assessment and treatment of men's sexual dysfunction were developed. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of the medical literature, in addition to cultural and ethical considerations. RESULTS: Recommendations and guidelines for men's sexual dysfunction are presented. These guidelines were developed as evidence-based, patient-centered, and multidisciplinary in focus. For the clinical assessment and diagnosis of ED, a basic evaluation was recommended for all patients, with optional and specialized testing reserved for special cases. A new treatment algorithm is proposed. This algorithm provides a clinically relevant guideline for managing ED in the large majority of men. New treatment guidelines and algorithms are provided for men's orgasm and ejaculation disorders, including premature ejaculation, retrograde and delayed ejaculation. Finally, expert opinion-based guidelines for the clinical management of priapism and Peyronie's disease are provided. CONCLUSIONS: Additional research is needed to validate and extend these guidelines. Nonetheless, this summary encompasses the recommendations concerning men's sexual dysfunctions presented at the 2nd International Consultation on Sexual Medicine in Paris, France, June 28-July 1, 2003.
INTRODUCTION: Endocrine disorders of sex steroid hormones may adversely affect men's sexual function. Aim. To provide expert opinions/recommendations concerning state-of-the-art knowledge for the pathophysiology, diagnosis and treatment of endocrinologic sexual medicine disorders. METHODS: An International Consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a scientific and debate process. Concerning the Endocrine committee, there were eight experts from seven countries. MAIN OUTCOME MEASURE: Expert opinions/recommendations are based on grading of evidence-based medical literature, extensive internal committee discussion over 2 years, public presentation and deliberation. RESULTS: Hypogonadism is a clinical and biochemical syndrome characterized by a deficiency in serum androgen levels which may decrease sexual interest, quality of erections and quality of life. Biochemical investigations include testosterone and either bioavailable or calculated free testosterone; prolactin should be considered when hypogonadism has been documented. If clinically indicated, androgen therapy should maintain testosterone within the physiological range avoiding supraphysiologic values. Digital rectal examination and determination of serum prostate specific antigen values are mandatory prior to therapy and regularly thereafter. Androgen therapy is usually long-term requiring regular follow-up, frequent monitoring of blood levels and beneficial and adverse therapeutic responses. CONCLUSIONS: Safe and effective treatments for endocrinologic sexual medicine disorders examined by prospective, placebo-controlled, multi-institutional clinical trials are needed.
The AmpFlSTR Identifiler kit has recently been accepted for use in DNA databasing of forensic samples in the FBI's National DNA Index System. In the present study, we used this kit to analyze the allele distribution of 15 short tandem repeat markers (STR) in individuals living in Caracas city, Venezuela. The allele frequencies of two of these STR, D2S1338 and D19S433, have not previously been reported for this or any other Latin American population. The results indicate that for the population here studied, the 15 STR tested are useful markers for paternity testing and forensic casework.
OBJECTIVES: To compare aspiration and sclerotherapy using sodium tetradecylsulfate (STDS) with open hydrocelectomy in the treatment of hydroceles with regard to safety, efficacy, and cost-effectiveness. METHODS: Patients with symptomatic hydroceles were prospectively enrolled in an aspiration and sclerotherapy protocol between October 1998 and June 2000. Patients in this group underwent percutaneous aspiration followed by sclerotherapy with an STDS-based solution. This group was compared with a group of patients chosen consecutively who underwent hydrocelectomy between December 1996 and August 1999. Primary outcome measures included patient satisfaction and procedural success. Secondary outcome measures included complications and comparative costs. RESULTS: A total of 27 patients with 28 hydroceles were enrolled in the aspiration and sclerotherapy protocol and compared with 24 patients with 25 hydroceles in the hydrocelectomy group. Mean follow-up for the aspiration and sclerotherapy group and hydrocelectomy group was 8.9 and 16.4 months, respectively. Patient satisfaction was 75% for aspiration and sclerotherapy and 88% for hydrocelectomy. The overall success rate for aspiration and sclerotherapy was 76% compared with 84% for hydrocelectomy. The complication rate was only 8% in the aspiration and sclerotherapy group, but 40% in the hydrocelectomy group. Comparative costs per procedure demonstrated that hydrocelectomy was almost ninefold more expensive than aspiration and sclerotherapy. CONCLUSIONS: In the treatment of hydroceles, aspiration and sclerotherapy with STDS represents a minimally invasive approach that is simple, inexpensive, and safe but less effective than hydrocelectomy. Aspiration and sclerotherapy is a viable first-line therapeutic option in the management of hydroceles.
The endocrine system has a major role in erections in normal men and it can also be a cause of significant morbidity. The relationship between serum testosterone measurement and erectile function is complex. Androgen treatment should certainly be considered in patients without prostate cancer but with a clinical picture that suggests a relevant contribution of hypogonadism to the ED. Other, nondiabetic, endocrine abnormalities may need to be considered in the management or the patient with ED.
The treatment of male sexual dysfunction in the elderly offers special challenges. Commonly, these men have other conditions requiring medical treatment and the possibility of adverse drug interactions is common. Similarly, the severity of dysfunction is frequently increased by alteration in various organ systems. For instance, ED is commonly associated with significant cardiovascular problems and hormonal alterations. The treatment of these men requires familiarity with the various options available and good clinical judgment to determine when and how modification of therapeutic regimens and combinations of specific drugs may provide the best responses. Frequently one hears the embarrassed older man coming for a consultation and stating that, "At my age, I should not be thinking of this." It is imperative to remember that advancing age does not preclude sexual interest and desire for performance. A well-informed, understanding physician can provide sound advice, institute appropriate therapies, and organize intelligent referrals.
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In men, gonadal function is affected in a slow, progressive way as part of the normal ageing process. Recently, however, significant interest has developed on the importance of this condition, which is variously known as male climacteric, andropause or, more appropriately, androgen decline in the ageing male (ADAM). The term andropause is biologically wrong and clinically inappropriate but, it adequately conveys the concept of emotional and physical changes that, although related to ageing in general, are also associated with significant hormonal alterations. The inappropriateness of the term is based on the fact that in women, the reproductive cycle invariably ends with ovarian failure. In men, this process is not universal and when it occurs it is normally subtle in its clinical manifestations. This has led to a tendency to ignore the syndrome as an unavoidable and untreatable result of the ageing process. For the sake of simplicity and directness, this review will use the terms ADAM and andropause to denote the global hormonal alterations associated with ageing.
OBJECTIVES: To compare the effectiveness of two rapid urine tests fibrinogen/fibrin degradation products FDP (Aura Tek FDP, PerImmune Inc., Rockville, Maryland, USA) and bladder tumor antigen BTA (Bard BTA, Bard Canada Inc., Mississauga, Ontario, Canada) to urinary cytology in establishing the diagnosis of transitional cell carcinoma (TCC) in patients with suspected upper tract malignancy. MATERIALS AND METHODS: In a prospective study, urine samples were collected from 29 patients with abnormalities of the upper tracts highly suspicious for malignancy. Sensitivity and specificity of the BTA and FDP tests were determined and compared to those of cytology. All persons interpreting the individual tests were blinded to the other test results. RESULTS: Of the 29 patients evaluated, 14 were found to have upper tract TCC. The overall sensitivity of FDP, BTA and urinary cytology was found to be 100%, 50% and 29%, respectively. The accuracy of the FDP test was 83% as compared to 62% for BTA and 59% for cytology. CONCLUSION: Urinary cytology lacks sensitivity in the diagnosis of upper tract TCC. This preliminary study suggests that the point-of-care test, FDP, has better test characteristics than urinary cytology. Further evaluation of these tests is warranted for their potential to improve and facilitate the diagnosis of upper tract tumors.