Andrew Harbin

5-Alpha Reductase Inhibitors and Erectile Dysfunction: The Connection

INTRODUCTION Benign prostatic hyperplasia (BPH) is a common problem affecting middle-aged and elderly men. First-line medical therapy includes alpha 1blockers and 5alpha-reductase inhibitors (5ARIs), such as finasteride and dutasteride. 5ARI use has been associated with adverse sexual outcomes, including erectile dysfunction (ED), ejaculatory dysfunction (EjD), and decreased libido. AIM To clarify the association between sexual adverse effects (AEs) and 5ARIs through review of literature concerning 5ARIs and to review the proposed mechanisms of these effects. METHODS A comprehensive literature review, using MEDLINE and PUBMED search engines, was conducted for all publications concerning 5ARIs and sexual AEs. MAIN OUTCOME MEASURE Sexual adverse effects, such as ED, EjD, and decreased libido, were the measured outcomes of this literature review. RESULTS Sexual AEs are reported in clinical trials at rates of 2.1% to 38%. The most common sexual AE is ED, followed by EjD and decreased libido. These effects occur early in therapy and attenuate over time. A proposed mechanism for sexual dysfunction involves decreased nitric oxide synthase activity due to decreased dihydrotestosterone. CONCLUSIONS The connection between 5ARIs and sexual dysfunction is apparent upon review of the literature. Though theories have been proposed, little is known about the exact mechanisms behind 5ARI-related sexual dysfunction. Since the connection between 5ARIs and sexual AEs is established in the literature, future research should be directed toward deciphering the pathophysiologic mechanisms. When more basic science knowledge is attained in this area, the focus can shift toward prevention and treatment.

The Effects of Chronic 5‐Alpha‐Reductase Inhibitor (Dutasteride) Treatment on Rat Erectile Function

INTRODUCTION Numerous clinical series have reported an association between 5-alpha-reductase inhibitors (5ARIs) and sexual dysfunction, but there are limited preclinical data available. AIM To further investigate the mechanisms of erectile dysfunction (ED) related to 5ARI therapy using a rat model. MAIN OUTCOME MEASURES Outcome measures include serum dihydrotestosterone (DHT), relaxant and contractile properties of cavernosal muscle, and nitric oxide synthase expression. METHODS Twenty adult male Sprague-Dawley rats were randomized into control (N = 10) and dutasteride (0.5 mg/rat/day, in drinking water, N = 10) groups. Serum samples were obtained at baseline, from which DHT was measured after 30 days of treatment via radioimmunoassay (Beckman Coulter, Fullerton, CA, USA). Before the terminal blood draw, erectile response was measured using cavernosal nerve stimulation. The relaxant and contractile properties of cavernosal muscle strips were evaluated in tissue baths, and immunohistochemical (IHC) staining for nitric oxide synthase (NOS) and collagen deposition was performed. RESULTS Mean serum DHT was suppressed by 86.5% (range 64.2-94.8%) after 30 days of 5ARI treatment and was statistically significant (P = 0.0024). In vivo erectile response in the dutasteride treated group decreased significantly compared with control (P < 0.001). While electrical field stimulation (EFS)-induced and acetylcholine-induced relaxation was decreased, EFS-induced and phenlyephrine-induced adrenergic contraction was significantly enhanced in the dutasteride group (P < 0.01). IHC studies demonstrated increased collagen deposition in the treatment arm as well as altered expression of neuronal NOS (nNOS) and inducible NOS (iNOS). CONCLUSIONS The 5ARIs, as demonstrated in these rat cavernosal smooth muscle studies, have a detrimental effect on erectile function. Enhanced iNOS expression may protect penile smooth muscle from fibrosis. The effect of 5ARIs on human sexual function warrants further investigation.

Chronic inhibition of nitric-oxide synthase induces hypertension and erectile dysfunction in the rat that is not reversed by sildenafil

Study Type – Aetiology (case control)
Level of Evidence 3b

Oncocytic Adrenocortical Neoplasm Diagnosed after Robot-Assisted Adrenalectomy.

Oncocytic tumors, composed of eosinophilic, mitochondria-rich cells, can occur in several locations throughout the body. These tumors can occur in the adrenal cortex and are rarely malignant. We report a case of a patient presenting with an incidental adrenal mass which was later diagnosed as a oncocytic adrenocortical neoplasm (OAN). The patient is a 53-year-old man found to have a 7.2 cm right adrenal mass, incidentally found by computed tomography (CT). After metabolic workup was negative, a right robotic adrenalectomy (RA) was performed. Pathologic analysis revealed clusters of large cells with abundant eosinophilic and granular cytoplasm, consistent with OAN. This pathology is rare, with only about 150 cases described in the literature. It occurs in females 2.5 times more frequently and more commonly on the left side. Diagnosis is usually made by imaging criteria, typically with CT or magnetic resonance imaging (MRI). Treatment is generally surgical, since OAN can be malignant in some cases. Differentiation between benign and malignant OAN is done based on the Lin-Weiss-Bisceglia criteria and can be difficult. If malignancy is diagnosed, recurrence is common and close surveillance should be performed.

The Penile Prosthesis Option for Erectile Dysfunction

Erectile dysfunction (ED) treatment can be divided into three main categories. These are oral agents, intracavernosal and intraurethral therapies, and local devices, such as vacuum and penile prosthesis. The first-line treatment for ED is oral phosphodiesterase type 5 inhibitors (PDE5Is); second-line treatment options include any combination of intracavernosal agents, such as papaverine, phentolamine, PGE1, or transurethral alprostadil. For this reason, penile prosthesis continues to be an important form of treatment for ED. Penile prosthesis implantation is a highly effective treatment option which yields high success rates, increased patient satisfaction, and low complication rates for men who fail first- and second-line treatment. Penile prostheses are indicated in a variety of conditions which cause ED, such as diabetes mellitus (DM), Peyronie’s disease, corporal fibrosis following priapism, ED following radical prostatectomy for prostate cancer and spinal cord injury.