'Up and coming' treatments for premature ejaculation: progress towards an approved therapy.

It is generally accepted that premature ejaculation (PE) is a more common problem than erectile dysfunction, although at present the options currently available for the treatment of PE are limited to behavioural psychotherapy and 'off-label' prescribing of pharmacological therapies. A sexual complaint with such a high prevalence together with an increasing understanding of the psychosocial consequences of PE has naturally stimulated the interest of the pharmaceutical industry and the first products designed specifically for the treatment of PE are either in late-stage clinical development or are already under regulatory review. Most of the new treatments for PE have been developed for 'on-demand' use, which may prove to offer the most favourable risk: benefit profile as well as the flexibility to adapt to differing frequencies of sexual activity. This paper reviews a number of emerging therapies in various stages of development that show potential for use in the treatment of PE.

Not all brands are created equal: a comparison of selected components of different brands of Serenoa repens extract.

Recommendations regarding the use of plant-derived medications for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) state that every brand should be fully evaluated and considered separately. Disparity between a number of brands in terms of their stated and actual doses has been recently highlighted. The aim of this study was to fully quantify the variation in Serenoa repens extracts (SrE) commercially available for the treatment of BPH-associated LUTS. To this end, 14 brands of SrE were compared. Concentrations of free fatty acids (FFAs), methyl and ethyl esters, long-chain esters and glycerides were assessed using liquid and gas chromatography. Many of the brands showed a significantly different proportional content which may have an impact on their clinical efficacy and safety. The high concentrations of FFAs in particular, which previous research has suggested as comprising the active agent of SrE for the treatment of LUTS, may influence the clinical benefit derived from each product. Our findings lend further weight to recommendations by the 5th International Consultation on BPH that plant-derived treatments should be analysed and considered as independent entities despite their common origin. Only extracts with demonstrated pharmacological activities and proven clinical efficacy should be considered for the treatment of patients with BPH.

Directions in urological research and drug therapies.

This meeting report summarizes advances and notable developments in the pharmaceutical management of urological diseases presented at various sessions during the Annual Meeting of the American Urological Association held in Anaheim, California, June 2-7, 2001. More than 10,000 attendees drawn from clinical and preclinical research deliberated on the latest trends in surgical and pharmacotherapeutic management in diverse areas of urology. In particular, several forums were dedicated to reviewing scientific trends, emerging concepts and therapies in urological diseases, such as overactive bladder, erectile dysfunction and lower urinary tract symptoms, which are the focus of this report.

Clinical trials design: protocols and endpoints.

Over the last decade there has been a proliferation in clinical trials to test agents for the treatment of erectile dysfunction (ED). Many aspects of clinical trials design and conduct and guidelines for future conduct have been the subject of a recent comprehensive review (Rosen R et al. In: Proceedings of the 1st International Consultation on Erectile Dysfunction 1999). The present article attempts to extend that analysis from trials that focus purely on symptomatic improvement of ED to trials relevant to the management of the ED patient in the community. Although the regulatory approval process accounts for the bulk of the clinical trials undertaken, studies are also initiated for concept testing, post-marketing surveillance and for promotional and/or pricing reasons. The trial design can be dependent on which of the above objectives is being served. However, there are also many common features that are summarized below; the major focus is placed on regulatory-standard or 'pivotal' studies. International Journal of Impotence Research (2000) 12, Suppl 4, S53-S58.

alpha1-adrenoceptor selectivity: the North American experience.

OBJECTIVE: The recent publication of multicentre US studies raises the possibility that the response to tamsulosin is dose-related and less than maximum at 0.4 mg. The objective of the present study was to calculate pharmacologically equivalent, alpha-blocking doses of doxazosin and tamsulosin in a clinical setting and thereby to examine further the concept of 'uroselectivity' and 'prostate selectivity'. METHODS: Healthy male volunteers were monitored in controlled, crossover studies. The effects of placebo or alpha blocker on phenylephrine (PE)-induced urethral and vascular responses, were determined. These were related to plasma drug concentrations and used with in vitro radioligand binding data to derive receptor occupancy. RESULTS: Doxazosin effectively blocked PE-induced vascular and urethral changes over the dose range 1-16 mg. There was no evidence for target organ selectivity. The degree of blockade of the PE-induced responses by tamsulosin was highly dependent on the time of measurement, post drug administration. The degree of observed blockade with tamsulosin at 0.4 mg was substantially less than that observed at 0.8 mg tamsulosin and/or 1 mg doxazosin. CONCLUSIONS: These studies provide no evidence of prostate selectivity for tamsulosin. 0.4 mg tamsulosin is a sub-optimal blocking dose and is equivalent to 1 mg of doxazosin and terazosin (1-2 mg). It is recommended that future comparative studies on benefit/risk in patients should include a range of doses encompassing the ED50.