Androgen Replacement in Men with Hypogonadism and Erectile Dysfunction
Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, United States Endocrine
(Impact Factor: 3.88).
03/2004; 23(2-3):143-8. DOI: 10.1385/ENDO:23:2-3:143
The prevalence of hypogonadism and erectile dysfunction (ED) increases with age. Hypogonadism also is frequently associated with decreased libido and ED. Testosterone replacement therapy for hypogonadal ED is effective in restoring sexual desire and erectile function, especially in younger and healthy men. It appears to be less effective in older men with comorbid diseases that may cause ED. Therapy should be individualized, considered carefully, and closely monitored because of potential risks, especially in older men. The FDA has approved several testosterone delivery systems. These include a buccal testosterone tablet, intra-muscular injections, transdermal and subcutaneous forms. There also are several promising experimental androgens under investigation including non-steroidal selective androgen receptor modulators (SARMs).
Available from: clinsci.org
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ABSTRACT: Penile erection is a complicated event involving the regulation of corpus cavernosal smooth muscle tone. Recently, the small monomeric G-protein RhoA and its downstream effector Rho-kinase have been proposed to be important players for mediating vasoconstriction in the penis. RhoA/Rho-kinase increases MLC (myosin light chain) phosphorylation through inhibition of MLCP (MLC phosphatase) thereby increasing Ca2+ sensitivity. This review will outline the RhoA/Rho-kinase signalling pathway, including the upstream regulators, guanine nucleotide exchange factors, GDP dissociation inhibitors and GTPase-activating proteins. We also summarize the current knowledge about the physiological roles of RhoA/Rho-kinase in both male and female erectile tissues and its aberrations contributing to erectile dysfunction in several disease states. Understanding the RhoA/Rho-kinase signalling pathway in the regulation of erection is important for the development of therapeutic interventions for erectile dysfunction.
Clinical Science 03/2006; 110(2):153-65. DOI:10.1042/CS20050255 · 5.60 Impact Factor
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ABSTRACT: To evaluate whether combination therapy with testosterone gel (T-gel) and sildenafil citrate is effective in achieving adequate potency in subjects with low-normal serum testosterone levels in whom sildenafil alone has failed.
From July 2000 to June 2001, we evaluated 90 men (aged 32 to 72 years) in whom 3 months of sildenafil therapy at the maximal recommended dose (100 mg) with at least three attempts at intercourse during the 3-month period had failed. Of these, 24 men had testosterone levels less than 400 ng/dL (range 92 to 365, mean 231.4) and were subsequently started on 1% T-gel monotherapy (AndroGel, 5 g daily). After 4 weeks of T-gel alone (week 4), sildenafil citrate (Viagra, 100 mg) was added to the treatment regimen for an additional 12 weeks (through week 16). Potency was defined as the ability to have at least one episode of satisfactory intercourse during the treatment period.
All the men had normalized serum testosterone levels after 4 weeks of T-gel monotherapy (range 424 to 596 ng/dL, mean 525). However, none of the men regained potency. At week 16, almost all (22 of 24, 92%) of the men reported improved potency with combination therapy. Improvement in erection quality was also observed.
The results of this study support the use of T-gel with sildenafil citrate in men with low-normal serum testosterone levels in whom sildenafil alone fails. It also underscores the numbers of men with low to low-normal testosterone levels who would benefit from testosterone screening when evaluated for erectile dysfunction.
Urology 04/2006; 67(3):571-4. DOI:10.1016/j.urology.2005.09.032 · 2.19 Impact Factor
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ABSTRACT: Androgens are deemed critical for penile-tissue development, growth, and maintenance of erectile function, however, their role in erection, especially in humans, remains controversial. In this review, we summarize information from clinical and animal model studies to provide a comprehensive and rational argument for the role of androgens, or lack thereof, on penile erection ability in humans. The goal of this review is to present the clinical and preclinical evidence available in the literature with regard to testosterone and erectile physiology and engage the reader in this discussion. Ultimately, each reader will have to form his or her own conclusions based on the existing evidence.
In humans, androgen-deficiency manifestations are noted in clinical situations such as: (i) inadequate development of the penis; and (ii) loss of erectile function in prostate cancer and benign prostatic hyperplasia patients managed with medical or surgical castration or antiandrogen therapy. Androgen treatment causes: (i) improvement in sexual function in hypogonadal patients treated with androgen supplementation; (ii) improvement in nocturnal penile tumescence in hypogonadal patients treated with androgens; (iii) improvement in erectile function with androgen supplementation in patients who did not respond to phosphodiesterase type 5 inhibitor therapy initially; and (iv) improvement in the well-being, mood, energy, and sexual function in aging men who have testosterone deficiency treated with androgen therapy. In contrast to animals, especially rodents in which the adrenal cortex does not synthesize androgens, the human adrenal is a source of peripherally circulating androgen precursors, thus, complete androgen insufficiency may not be observed in men at a younger age. Furthermore, in light of the concept that a threshold of androgen levels exists in animals and humans below which sexual function is diminished, further contributes to the complexity of understanding androgens role in erections, especially in humans. Nevertheless, based on the preclinical and clinical data available in the literature, to date, we infer that androgens play a critical role in maintaining erectile physiology in humans. Traish AM, and Guay AT. Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence. J Sex Med 2006;3:382–407.
Journal of Sexual Medicine 06/2006; 3(3):382-404; discussion 404-7. DOI:10.1111/j.1743-6109.2006.00245.x · 3.15 Impact Factor
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