ROLE OF TESTOSTERONE IN THE TREATMENT OF ED

Hypogonadism may play a significant role in the pathophysiology of erectile dysfunction (ED). A threshold level of testosterone may be necessary for normal erectile function. Testosterone replacement therapy is indicated in hypogonadal patients and is beneficial in patients with ED and hypogonadism. Monotherapy with testosterone for ED is of limited effectiveness and may be most promising in young patients with hypogonadism and without vascular risk factors for ED. A number of laboratory and human studies have shown the combination of testosterone and other ED treatments, such as phosphodiesterase type 5 (PDE5) inhibitors, to be beneficial in patients with ED and hypogonadism, who fail PDE5 inhibitor therapy alone. There is increasing evidence that combination therapy is effective in treating the symptoms of ED in patients for whom treatment failed with testosterone or PDE5 inhibitors alone. Testosterone replacement therapy has potentially evolved from a monotherapy for ED in cases of low testosterone, to a combination therapy with PDE5 inhibitors. Screening for hypogonadism may be useful in men with ED who fail prior PDE5 inhibitors, especially in populations at risk for hypogonadism such as type 2 diabetes and the metabolic syndrome

On the pathogenesis of penile venous leakage: role of the tunica albuginea

<p>Abstract</p> <p>Background</p> <p>Etiology of venogenic erectile dysfunction is not exactly known. Various pathologic processes were accused but none proved entirely satisfactory. These include presence of large venous channels draining corpora cavernosa, Peyronie's disease, diabetes and structural alterations in fibroblastic components of trabeculae and cavernous smooth muscles. We investigated hypothesis that tunica albuginea atrophy with a resulting subluxation and redundancy effects venous leakage during erection.</p> <p>Methods</p> <p>18 patients (mean age 33.6 ± 2.8 SD years) with venogenic erectile dysfunction and 17 volunteers for control (mean age 31.7 ± 2.2 SD years) were studied. Intracorporal pressure was recorded in all subjects; tunica albuginea biopsies were taken from 18 patients and 9 controls and stained with hematoxylin and eosin and Masson's trichrome stains.</p> <p>Results</p> <p>In flaccid phase intracorporal pressure recorded a mean of 11.8 ± 0.8 cm H₂O for control subjects and for patients of 5.2 ± 0.6 cm, while during induced erection recorded 98.4 ± 6.2 and 5.9 ± 0.7 cmH₂O, respectively. Microscopically, tunica albuginea of controls consisted of circularly-oriented collagen impregnated with elastic fibers. Tunica albuginea of patients showed degenerative and atrophic changes of collagen fibers; elastic fibers were scarce or absent.</p> <p>Conclusion</p> <p>Study has shown that during erection intracorporal pressure of patients with venogenic erectile dysfunction was significantly lower than that of controls. Tunica albuginea collagen fibers exhibited degenerative and atrophic changes which presumably lead to tunica albuginea subluxation and floppiness. These tunica albuginea changes seem to explain cause of lowered intracorporal pressure which apparently results from loss of tunica albuginea veno-occlusive mechanism. Causes of tunica albuginea atrophic changes and subluxation need to be studied.</p

Estradiol and Bisphenol A Stimulate Androgen Receptor and Estrogen Receptor Gene Expression in Fetal Mouse Prostate Mesenchyme Cells

doi:10.1289/ehp.9804Hormonal alterations during development have lifelong effects on the prostate gland. Endogenous estrogens, including 17β-estradiol (E2), and synthetic estrogenic endocrine disruptors, such as bisphenol A (BPA), have similar effects on prostate development. Increasing exposure to estrogens within the low-dose, physiologic range results in permanent increases in the size and androgen responsiveness of the prostate, whereas exposure within the high-dose, pharmacologic range has the opposite effects

Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase.

OBJECTIVES: We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. MATERIALS AND METHODS: Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry. RESULTS: When compared with the control group, the COMB-4 group exhibited 46% higher maximum strength (t-test, p = 0.029) and 92% higher stiffness (t-test, p = 0.023), but no significant changes were observed in the tadalafil group. At days 14 and 42, there was no significant difference between the three groups with respect to callus volume, mineral content and bone density. Expression of iNOS at day 14 was significantly higher in the COMB-4 group which, as expected, had returned to baseline levels at day 42. CONCLUSION: This study demonstrates an enhancement in fracture healing by an oral natural product known to augment iNOS expression.Cite this article: R. A. Rajfer, A. Kilic, A. S. Neviaser, L. M. Schulte, S. M. Hlaing, J. Landeros, M. G. Ferrini, E. Ebramzadeh, S-H. Park. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase. Bone Joint Res 2017:6:-97. DOI: 10.1302/2046-3758.62.BJR-2016-0164.R2

Partial Priapism Treated with Pentoxifylline

ABSTRACTMain findings:A 26-year-old man suffering from partial priapism was successfully treated with a regimen including pentoxifylline, a nonspecific phosphodiesterase inhibitor that is often used to conservatively treat Peyronie's disease.Case hypothesis:Partial priapism is an extremely rare urological condition that is characterized by thrombosis within the proximal segment of a single corpus cavernosum. There have only been 36 reported cases to date. Although several factors have been associated with this unusual disorder, such as trauma or bicycle riding, the etiology is still not completely understood. Treatment is usually conservative and consists of a non-steroidal anti-inflammatory and anti-thrombotic.Promising future implications:This case report supports the utilization of pentoxifylline in patients with partial priapism due to its anti-fibrogenic and anti-thrombotic properties

Stress Affects a Gastrin-Releasing Peptide System in the Spinal Cord That Mediates Sexual Function: Implications for Psychogenic Erectile Dysfunction

Many men suffering from stress, including post-traumatic stress disorder (PTSD), report sexual dysfunction, which is traditionally treated via psychological counseling. Recently, we identified a gastrin-releasing peptide (GRP) system in the lumbar spinal cord that is a primary mediator for male reproductive functions.To ask whether an acute severe stress could alter the male specific GRP system, we used a single-prolonged stress (SPS), a putative rat model for PTSD in the present study. Exposure of SPS to male rats decreases both the local content and axonal distribution of GRP in the lower lumbar spinal cord and results in an attenuation of penile reflexes in vivo. Remarkably, pharmacological stimulation of GRP receptors restores penile reflexes in SPS-exposed males, and induces spontaneous ejaculation in a dose-dependent manner. Furthermore, although the level of plasma testosterone is normal 7 days after SPS exposure, we found a significant decrease in the expression of androgen receptor protein in this spinal center.We conclude that the spinal GRP system appears to be a stress-vulnerable center for male reproductive functions, which may provide new insight into a clinical target for the treatment of erectile dysfunction triggered by stress and psychiatric disorders