trelstar and Erectile-Dysfunction

Inhibition of phosphodiesterase-5 (PDE5) is a well-known mechanism for the effective treatment of erectile dysfunction (ED). Androgen supplementation has also been prescribed for treating ED. However, it has been widely accepted that androgen can upregulate PDE5 expression, and thus creating a paradox in which a positive regulator of erectile function (androgen) could possibly increase the level of a negative regulator (PDE5). To solve this paradox, we conducted a systematic search of the PubMed and a non-systematic search of the Internet using PDE5, erectile, penis, testosterone and androgen as keywords. The retrieved papers were analyzed for data concerning the expression and regulation of PDE5 by androgens. Human and rat PDE5A gene sequences were retrieved from GenBank and computer-analyzed. The results showed that a putative androgen-response element (ARE) was reported in a study of human PDE5A gene promoter, and this prompted a separate study on whether androgen regulates PDE5 expression. The positive outcome in the latter study has since been cited in 17 review and editorial articles as the underlying mechanism for androgen's therapeutic effects on ED. In addition, five other research studies also reached the same conclusion. On the other hand, two independent studies on the genome-wide searches for androgen-regulated genes did not find PDE5A as a candidate. Sequence analysis conducted in this study also failed to find ARE in rat PDE5A gene. Two independent studies on Leydig cells also failed to find positive regulation of PDE5 expression by androgen. Two other studies found concomitant reduction of cavernous smooth muscle and PDE5 expression in castrated rats. One of these studies also found no effect of androgen on PDE5 expression in cultured cavernous smooth muscle cells. Thus, it appears that reduced PDE5 expression in castrated animals is due to reduced smooth muscle content and that PDE5A gene is not directly regulated by androgens.

Topics: Androgens; Animals; Base Sequence; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Gene Expression Regulation; Humans; Leydig Cells; Male; Myocytes, Smooth Muscle; Orchiectomy; Penile Erection; Penis; Phosphodiesterase Inhibitors; Promoter Regions, Genetic; Rats; Response Elements; RNA, Messenger; Sequence Alignment; Triptorelin Pamoate

Men with deviant sexual behavior, or paraphilia, are usually treated with psychotherapy, antidepressant drugs, progestins, and antiandrogens, but these treatments are often ineffective. Selective inhibition of pituitary-gonadal function with a long-acting agonist analogue of gonadotropin-releasing hormone may abolish the deviant sexual behavior by reducing testosterone secretion.. In an uncontrolled observational study, we treated 30 men (mean age, 32 years) with severe long-standing paraphilia (25 with pedophilia and 5 with other types of abnormal behavior) with monthly injections of 3.75 mg of triptorelin and supportive psychotherapy for 8 to 42 months. The efficacy of therapy was evaluated monthly by the Intensity of Sexual Desire and Symptoms Scale and yearly by the Three Main Complaints questionnaire.. All the men had a decrease in the number of deviant sexual fantasies and desires, from a mean (+/-SD) of 48+/-10 per week before therapy to zero during therapy (P<0.001), and a decrease in the number of incidents of abnormal sexual behavior (from 5+/-2 per month to zero, P<0.001) while receiving triptorelin. These effects were evident after 3 to 10 months of therapy (P<0.001) and persisted in all 24 men who continued therapy for at least 1 year. The men's mean serum testosterone concentration fell from 545+/-196 ng per deciliter (18.9+/-6.8 nmol per liter) before therapy to 23+/-14 ng per deciliter (0.8+/-0.5 nmol per liter, P<0.001) after 42 months of triptorelin. The main side effects were erectile failure, hot flashes, and decrease in bone mineral density in some men.. Continuous administration of triptorelin, a long-acting agonist analogue of gonadotropin-releasing hormone, together with supportive psychotherapy, may be an effective treatment for men with severe paraphilia.

Topics: Adult; Bone Density; Erectile Dysfunction; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Paraphilic Disorders; Testis; Testosterone; Treatment Outcome; Triptorelin Pamoate