Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction

Aversa, Antônio; Isidori, Andrea M.; Martino, M. U. De; Caprio, Massimiliano; Fabbrini, Elisa; Rocchietti-March, M.; Frajese, Gaetano; Fabbri, Andrea

doi:10.1046/j.1365-2265.2000.01118.x

Cited by 181 publications

(146 citation statements)

References 40 publications

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“…65,[88][89][90] In men with erectile dysfunction, low free testosterone levels correlate with impaired relaxation of cavernous endothelial and corporeal smooth muscle cells to a vasoactive challenge. 91 A direct effect of testosterone is feasible as testosterone modulates expression of endothelial nitric oxide synthase and phosphodiesterase type 5 (PDE5) within penile tissues. [92][93][94] Testosterone therapy can improve IIEF scores in men who do not respond to PDE5 inhibitors by improving sexual desire and orgasmic function and increasing penile arterial inflow during sexual stimulation.…”

Section: Testosterone and Sexual Health In Aging Menmentioning

confidence: 99%

Are declining testosterone levels a major risk factor for ill-health in aging men?

Yeap

2008

Int J Impot Res

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As men grow older, testosterone levels fall, with a steeper decline in unbound or free testosterone compared with total testosterone concentrations. Lower testosterone levels have been associated with poorer cognitive function, and with impaired general and sexual health in aging men. Recently, lower testosterone levels have been linked with metabolic syndrome and type II diabetes, both conditions associated with cardiovascular disease, and shown to predict higher overall and cardiovascular-related mortality in middle-aged and older men. However, reverse causation has to be considered, as systemic illness may result in reduced testosterone levels. Thus, the strength of these associations and the likely direction of causation need to be carefully considered. Furthermore, these conditions may overlap, for example aging, lower testosterone levels, erectile dysfunction and cardiovascular disease are interrelated. Cross-sectional and longitudinal observational studies may be informative. However, ultimately randomized controlled trials of testosterone therapy are needed to clarify its role in the maintenance of general and sexual health in aging men. Testosterone therapy should be considered in hypogonadal men who meet rigorous criteria for the diagnosis of androgen deficiency. Additional consideration should be given to designing and testing interventions that may prevent or ameliorate the age-related decline in testosterone levels in men.

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Section: Testosterone and Sexual Health In Aging Menmentioning

confidence: 99%

Are declining testosterone levels a major risk factor for ill-health in aging men?

Yeap

2008

Int J Impot Res

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“…Clinical and animal studies provided evidence that androgens protect cavernous SM, promoting cell proliferation and maintaining functional integrity (Andersson and Wagner 1995;Aversa et al 2000Aversa et al , 2003Garban et al 1995;Huang et al 2008;Lue and Dahiya 1997;Mills et al 1992;Shabsigh 1997). It was also demonstrated that androgen deficiency contributes to endothelial damage in a castrated rat model (Lu et al 2007).…”

mentioning

confidence: 98%

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Tomada

Almeida

et al. 2011

AGE

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Aging and physiological androgen decay leads to structural changes in corpus cavernosum (CC) that associate with erectile function impairment. There is evidence that such changes relate to nitric oxide (NO) bioavailability, an endothelial compound produced by the action of endothelial NO synthase (eNOS), and is regulated by sirtuin-1 (Sirt1), a NAD + -dependent protein deacetylase. Taking into account the reduced NO synthesis observed in aging and erectile dysfunction, we aimed to characterize human CC of androgen-deprived, young, and aged individuals postulating that androgen deprivation induces modifications similar to those observed in aging. Human penile fragments were collected from young individuals submitted to male-to-female sex reassignment procedure, who undergone an androgen deprivation chemical regimen, from young organ donors and from aged patients submitted to penile deviation surgery. They were processed for histomorphometric analysis of smooth muscle (SM) and connective tissues (CT), and dual-immunofluorescence of alpha-actin/vWf or Sirt1, and endothelin-1/eNOS. Estrogen receptors were analyzed by immunohistochemistry and semiquantification of Sirt1, eNOS, and phospho-Akt was assayed by Western blotting. Androgen withdrawal, similarly to aging, leads to a noteworthy reduction of SM-to-CT ratio in CC. However, in contrast to young and aged, a significant increase in penile Sirt1 expression accompanied by an increase in total eNOS expression was observed in androgen-depleted individuals. No changes were evidenced in phospho-Akt system and estrogen receptors were undetectable. These findings indicate that Sirt1 regulates the expression of eNOS in human CC employing mechanisms influenced by androgen depletion.

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“…combination with sildenafil in these patients who have dual pathology. Recent data suggest that testosterone is a smooth muscle relaxant for the penile vessels 16 which is likely to potentiate the action of sildenafil. Although no properly conducted study is available to provide hard scientific data on the efficacy of combination therapy of TRT with sildenafil, improvement in libido may increase erectile performance, thereby self-correcting borderline testosterone insufficiency.…”

Section: Discussionmentioning

confidence: 99%

Management of erectile dysfunction by combination therapy with testosterone and sildenafil in recipients of high-dose therapy for haematological malignancies

Chatterjee

Kottaridis

Mcgarrigle

et al. 2002

Bone Marrow Transplant

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Summary:Erectile dysfunction (ED) is a well recognised complication of bone marrow transplantation, which affects quality of life in adult patients. Although the major contributory factors include hypogonadism and psychogenic factors, the best treatment still remains to be established due to the complex aetiopathology of the condition. Here, we report our preliminary results in eight patients treated with testosterone replacement therapy and sildenafil. We studied eight male recipients of BMT aged 22-58 years, presenting with clinical features of hypogonadism, ED, diminished libido and ejaculatory disorders. ED was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume, FSH, LH and testosterone (T) measurements. Erectile performance, libido and ejaculatory function were determined by a structured interview. Patients had severe primary hypogonadism as evidenced by low mean testicular volume, elevated gonadotrophins and low normal mean testosterone levels compared with controls. All had Leydig cell insufficiency (LCI) with or without frank serum testosterone insufficiency. All except one had cavernosal arterial insufficiency. All patients received intramuscular injections of testosterone cypionate (250 mg 4 weekly) for 6 months and 50-100 mg of sildenafil orally, one to two times per week. All patients responded favourably as substantiated from the NIH consensus criteria. Our preliminary results suggest that this combined therapy is a safe and effective therapeutic approach in recipients of high-dose therapy presenting with ED after transplant.

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Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction

Cited by 181 publications

References 40 publications

Are declining testosterone levels a major risk factor for ill-health in aging men?

Are declining testosterone levels a major risk factor for ill-health in aging men?

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Management of erectile dysfunction by combination therapy with testosterone and sildenafil in recipients of high-dose therapy for haematological malignancies

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