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PubMed2001

[Evidence based medicine with reference to the aging man].

There is increasing public and medical interest in the physiological changes of the ageing male. The intention for prolongation of life in combination with maintenance of physical and mental fitness are a great challenge for modern medicine. There are known alterations in the hormonal profiles of ageing males supporting the hypothesis of hormonal substitution to increase quality of life and even to prolong life. These therapies must be faced with the performance of evidence-based medicine defined by the combination of clinical experience with available scientific results including experimental and clinical investigations. There are several systems involved in the ageing process but the pathophysiological background for these changes is not completely understood. Some controlled, randomised studies reported positive effects of hormonal therapy in the ageing male but only a few investigated sufficient patients over a longer period. Due to the lack of long-term data, analysis of the literature for the application of evidence based medicine cannot be sufficiently done yet. It is necessary to perform experimental studies and clinical investigations on clearly defined questions concerning the ageing male including high number of patients over long term treatment periods to get sufficient data to evaluate the value of hormonal substitution in the ageing male according to evidence-based medicine criteria for the performance of best patient's care.

Adult↗
PubMed2002

Effects of the association of androgen/estrogen on the bladder and urethra of castrated rats.

PURPOSE: To study the effects of methyltestosterone, isolated or associated to estrogens, on the bladder and urethra of castrated adult rats. MATERIAL & METHODS: A total of 59 castrated animals were studied. They were divided into the following groups: I--placebo; II--equine conjugated estrogens; III--methyltestosterone and conjugated estrogens; IV--methyltestosterone. After 28 days of medication the animals were sacrificed and bladder and urethra cuts were obtained for the evaluation of the number of vessels, the thickness of the epithelia, and the quantity of collagen and muscular fibers. RESULTS: The group receiving the androgen/estrogen association presented a higher number of vessels, epithelial thickness and quantity of muscular fibers (p < 0.05). A smaller quantity of collagen fibers was observed in the group utilizing isolated conjugated estrogen (p < 0.05). CONCLUSION: We concluded that the association of androgen/estrogen positively modifies important parameters in the urinary continence mechanism. Therefore, it could constitute an option for hormone replacement in postmenopausal stress urinary incontinence cases.

Animals↗
PubMed2002

Gene therapy for prostate cancer by targeting poly(ADP-ribose) polymerase.

Poly(ADP-ribose) polymerase (PARP) has strong affinity for DNA strand breaks and cycles on and off the DNA ends to allow DNA repair. A DNA-binding domain of PARP (PARP-DBD) acts as a dominant-negative mutant by binding to DNA strand breaks irreversibly and sensitizing mammalian cells to DNA-damaging agents. Therefore, expression of PARP-DBD in prostate carcinoma cells offers a strategy to achieve sensitization to genotoxic treatments. Toward this end, we developed recombinant plasmids expressing the PARP-DBD under the control of the 5'-flanking sequences of the human prostate-specific antigen (PSA) gene. Tissue specificity of PARP-DBD expression in human tumor cells was confirmed using the PSA-producing (LNCaP) and PSA-negative (PC-3) prostate cancer cells, as well as cells of nonprostate origin, Ewing's sarcoma (A4573 cells). LNCaP cells stably transfected with the PSA-regulated cDNA for PARP-DBD exhibit an androgen-dependent induction of PARP-DBD expression as determined by Western blotting, reverse transcription-PCR, and in situ immunofluorescence. Furthermore, we found that PARP-DBD sensitized LNCaP cells to DNA-damaging agents, such as ionizing radiation and etoposide. Androgen (R1881) -dependent stimulation of PARP-DBD expression resulted in a 2-fold growth inhibition in LNCaP cells as compared with controls, and an augmented apoptotic cell death in response to ionizing radiation or etoposide. Taken together, the plasmid vector developed in this study permits the expression of the human PARP-DBD in an androgen-inducible and PSA-dependent fashion, and sensitizes prostatic adenocarcinoma cells to DNA-damaging treatments. These results provide proof-of-principle for a novel therapeutic strategy for the treatment of prostate cancer.

Adenocarcinoma↗
PubMed2002

Development of selective androgen receptor modulators and their therapeutic applications.

Androgens control a broad range of physiological functions. The androgen receptor (AR), a steroid receptor that mediates the diverse biological actions of androgens, is a ligand inducible transcription factor. Abnormalities in the androgen signaling system result in many disturbances ranging from changes in gender determination and sexual development to psychiatric and emotional disorders. Androgen replacement therapy can improve many clinical conditions including hypogonadism and osteoporosis, but is limited by the lack of efficacious and safe therapeutic agents with easy delivery options. Recent progress in the area of gene regulation by steroid receptors and by selective receptor modulators provides an opportunity to examine if selective androgen receptor modulators (SARMs) could address some of the problems associated with current androgen therapy. Since the composition of the transcriptional initiation complex recruited by liganded AR determines the specificity of gene regulation, synthetic ligands aimed at initiating transcription of tissue and promoter specific genes offers hope for developing better androgen therapy. Establishment of assays that predict synthetic ligand activity is critical for SARM development. Advancement in high throughput compound screening and gene fingerprinting technologies, such as microarrays and proteomics, will facilitate and accelerate identification of effective SARMs.

Androgen Antagonists↗
PubMed2002

Addition of testosterone to estrogen replacement therapy in oophorectomized women: effects on sexuality and well-being.

OBJECTIVE: To evaluate the effect of adding testosterone undecanoate 40 mg daily to estrogen replacement on sexual function, psychological well-being and self-esteem in surgically postmenopausal women. METHODS: A letter of invitation to participate in the study was mailed to women who had undergone hysterectomy and bilateral oophorectomy for benign disorders during 1990-98. Fifty women, 45-60 years old, were consecutively recruited and randomly assigned to oral treatment with testosterone undecanoate 40 mg plus estradiol valerate 2 mg daily or placebo plus estradiol valerate 2 mg daily for 24 weeks. A double-blind design was chosen, with cross-over to the other regimen for another 24 weeks of treatment. Forty-four women completed the study. Outcome included scores on McCoy's sex scale questionnaire, the Psychological General Well-Being index and a self-esteem questionnaire, at baseline and after 24 weeks of either treatment. Serum concentrations of total testosterone, sex hormone binding globulin, free testosterone, dihydrotestosterone, androstenedione, estradiol, follicle stimulating hormone and luteinizing hormone were analyzed at baseline and after 24 weeks of both treatment regimens. RESULTS: After 24 weeks, both treatment regimens had significantly improved some of the sexual variables. The addition of testosterone had a significantly better effect on the sex variables 'enjoyment of sex', 'satisfaction with frequency of sexual activity' and 'interest in sex'. The total McCoy score was significantly increased by both treatments, but there was a stronger effect when testosterone was also given. Although both regimens improved psychological well-being and self-esteem, we found no significant differences between testosterone-estrogen or estrogen alone at 24 weeks. Serum levels of all androgens, with considerable individual variation, increased significantly from baseline after 24 weeks of testosterone-estrogen treatment. Supraphysiological levels were achieved in a significant proportion of the women. Increases in estradiol and sex hormone binding globulin were less marked when testosterone was also given. Both treatments reduced gonadotropin levels. CONCLUSIONS: The addition of testosterone undecanoate improved specific aspects of sexual function more than treatment with estrogen alone. Improvements in well-being and self-esteem were similar for both treatments. If testosterone undecanoate 40 mg daily should be used for clinical treatment, regular monitoring of androgen serum levels is needed.

Cross-Over Studies↗
PubMedDate not supplied

[Correction of the microbiocoenosis of the male urogenital tract in the course of hormonal therapy].

The effect of androgenic preparations on the urogenital tract microflora in males of the reproductive age with chronic prostatitis has been studied. As the result of the use of androgens, the normalization of the microflora of ejaculate has been noted, which is characterized by the restoration of normal microflora (corynebacteria and lactic bacteria), a decrease in the content, or elimination, of opportunistic microorganisms and the inhibition of their persistence potential. The method for the correction of the dysbiosis of the male urogenital tract is proposed.

Adult↗
PubMed2003

Oral testosterone undecanoate (Andriol) supplement therapy improves the quality of life for men with testosterone deficiency.

In a single-blind, placebo-controlled study, the effects of a 3-month oral administration of 160 mg/day testosterone undecanoate (Andriol) on the quality of life of men with testosterone deficiency were evaluated. The subjects included ten men with primary hypogonadism and 29 with andropause with sexual dysfunction as the most common problem. The changes in subjective symptoms were evaluated by the PNUH QoL scoring system and the St. Louis University Questionnaire for androgen deficiency in aging males (ADAM). Digital rectal examination (DRE) was performed and serum testosterone, prostate-specific antigen (PSA) and liver profile were monitored. Testosterone undecanoate treatment (n = 33) significantly improved sexual dysfunction and symptom scores of metabolic, cardiopulmonary, musculoskeletal and gastrointestinal functions compared to baseline and to placebo (n = 6). ADAM score also significantly improved after 3 months of treatment. Serum testosterone was significantly increased compared to pretreatment levels only in the testosterone undecanoate group. In the placebo group, no significant changes compared to baseline were found for testosterone levels and QoL questionnaires. No abnormal findings were detected on DRE or laboratory findings in either group. Adverse events, such as gastrointestinal problems and fatigue, were mild and self-limiting. It is concluded that androgen supplement therapy with oral testosterone undecanoate (Andriol) restores the quality of life through improvement of general body functions in men with testosterone deficiency.

Administration, Oral↗
PubMed2003

Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone.

AIMS: To evaluate the cause of failure of sildenafil citrate (Viagra) to restore erections in patients with organic erectile dysfunction (ED) associated with type II diabetes mellitus (DM) and receiving oral antidiabetic drugs. METHODS: Diabetic ED patients (n = 120), aged 43-74 years, failing to respond at least three times to 100 mg Viagra were evaluated. After at least 2 weeks' treatment with oral testosterone undecanoate (Andriol), 100 mg Viagra was used before coitus. ED was assessed with the International Index of Erectile Function (IIEF). Serum total testosterone, prolactin, thyroid stimulating hormone, lipid profile and prostate-specific antigen (PSA) were determined by standard methods and prostate volume by digital rectal examination. Age-matched diabetic ED patients (n = 100) served as controls for baseline values. RESULTS: Viagra non-responders had, at baseline, significantly lower testosterone and more depressed libido than controls. Andriol restored testosterone to normal levels and increased libido. In 84/120 (70%) Viagra non-responders, combined therapy with Andriol induced satisfactory erections, a significant increase in IIEF scale (question (Q) 3 from 2.0 +/- 0.2 to 3.7 +/- 0.3, Q4 from 1.9 +/- 0.1 to 3.4 +/- 0.2, Q12 from 1.0 +/- 0.1 to 4.2 +/- 0.4) and increased sexual contacts from 0.5 to 3-4 per month. No adverse events were noted, and PSA levels remained below 4 ng/ml. CONCLUSION: Decreased testosterone levels in patients with ED and type II DM receiving oral antidiabetic against may be responsible for failure to respond to sildenafil citrate therapy. Combination with oral testosterone undecanoate restores sexual function in these patients.

Aged↗
PubMedDate not supplied

[Advances in the treatment of aplastic anemia].

The purpose of this paper is to describe the current advances in the pathogenesis, classification and treatment of acquired aplastic anemia (AA). The therapeutical experience obtained at the Servicio de Hematología, Centro Medico Nacional, Siglo XXI is described. Bone marrow transplantation is the first choice therapy for severe AA. This procedure succeeds in obtaining complete remission in nearly 80% of the cases. Nevertheless, few patients are eligible for such therapy, consequently other treatments should be considered. In this context some immunosuppressive therapies such as antilymphocyte globulin had shown to produce favorable responses in 60% of the patients. In addition, androgens and immunosuppressive drugs like methylprednisolone bolus and cyclosporin A do not have a definitive place in severe AA. Finally, it is important to describe the experience with lymphocytapheresis, a new procedure, that decreases the immunological response against the normal hematopoiesis by removing the population of T-lymphocytes inducing complete remission in a few patients.

Anemia, Aplastic↗
PubMed1955

[Anabolics].

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Proteins↗