A comprehensive history of injection therapy for erectile dysfunction, 1982-2023.

INTRODUCTION: Although oral phosphodiesterase 5 inhibitors represent a first choice and long-term option for about half of all patients with erectile dysfunction (ED), self-injection therapy with vasoactive drugs remains a viable alternative for all those who are not reacting or cannot tolerate oral drug therapy. This current injection therapy has an interesting history beginning in 1982. OBJECTIVES: To provide a comprehensive history of self-injection therapy from the very beginnings in 1982 by contemporary witnesses and some members of the International Society for Sexual Medicine's History Committee, a complete history of injection therapy is prepared from eyewitness accounts and review of the published literature on the subject, as well as an update of the current status of self-injection therapy. METHODS: Published data on injection therapy, as a diagnostic and therapeutic tool for ED, were reviewed thoroughly by PubMed and Medline research from 1982 until June 2023. Early pioneers and witnesses added firsthand details to this historical review. Therapeutic reports of injection therapy were reviewed, and results of side effects and complications were thoroughly reviewed. RESULTS: The pioneers of the first hours were Ronal Virag (1982) for papaverine, Giles Brindley (1983) for cavernosal alpha-blockade (phentolamine and phenoxybenzamine), Adrian Zorgniotti (1985) for papaverine/phentolamine, and Ganesan Adaikan and N. Ishii (1986) for prostaglandin E1. Moxisylyte (thymoxamine) was originally marketed but later withdrawn. The most common side effect is priapism, with the greatest risk of this from papaverine, which has modified its use for therapy. Currently, prostaglandin E1 and trimixes continue to be the agents of choice for diagnostic and therapeutic use in ED. A recent agent is a mixture of a vasoactive intestinal polypeptide (aviptadil) and phentolamine. CONCLUSIONS: After 40 years, self-injection therapy represents the medication with the highest efficacy and reliability rates and remains a viable option for many couples with ED. The history of this therapy is rich.

Erectile Dysfunction Resistant to Medical Treatment Caused by Cavernovenous Leakage: An Innovative Surgical Approach Combining Pre-operative Work Up, Embolisation, and Open Surgery.

OBJECTIVE: Thirty per cent of cases of erectile dysfunction (ED)/male impotence are resistant to oral treatment. Half of these cases are due to blood drainage from the corpora cavernosa occurring too soon, due to cavernovenous leakage (CVL). The aim of this study was to report on an innovative treatment scheme combining pre- and post-operative haemodynamic assessment, venous embolisation, and open surgery for drug resistant ED caused by CVL. METHODS: An analysis of prospectively collected data, with clinical and haemodynamic pre- and post-operative assessment, was carried out. Forty-five consecutive patients operated on for drug resistant ED caused by CVL were evaluated pre-operatively and three months post-operatively by pharmacologically challenged penile duplex sonography (PC-PDS), pharmacologically challenged Erection Hardness Score (PC-EHS), and pharmacologically challenged computed caverno tomography (PC-CCT). Follow up consisted of patient interview, PC-PDS, PC-EHS and if needed PC-CCT. RESULTS: Mean patient age was 43.9 ± 12.0 years (range 20-67). Forty-nine per cent of patients had primary ED. Patients with diabetes, a smoking habit, hypercholesterolaemia, and hypertension were 18%, 11%, 9%, and 4%, respectively. Three months post-operatively, PC-EHS increased from 2.0 ± 0.7 to 3.1 ± 0.74 (p < .001), with an EHS of 3 being the threshold allowing for penetration. Deep dorsal vein velocity, a haemodynamic marker of CVL, decreased from 14.2 ± 13.0 to 0.9 ± 3.5 cm/s (p < .001). After a 14.0 ± 10.7 month follow up, the primary success rate (clinical EHS ≥ 3, possible sexual intercourse with penetration, no vascular re-operation, no penile prosthesis implant) was 73.3%. Four patients (9%) underwent successful re-operation for persistent ED and CVL. Accordingly, compared with a possible penetration rate of 8.9% before surgery, 37 patients (secondary success rate: 82.2%) were able to achieve sexual intercourse with penetration. Type of ED (primary vs. secondary) and diabetes had no influence on the results. Thirty-two per cent of patients with secondary success achieved penetration with no medication. CONCLUSIONS: After a 14 month follow up, pre-operative work up, embolisation, and open surgery during the same procedure allowed patients with ED resistant to oral medical to achieve intercourse with penetration.

Differentially expressed angiogenic genes in diabetic erectile tissue - results from a microarray screening.

Diabetes-induced metabolic derangements promote endothelial malfunction, contributing to erectile dysfunction (ED). However, it remains unclear which angiogenic molecular mechanisms are deregulated in diabetic corpus cavernosum (CC). We investigated early and late alterations in cavernosal angiogenic gene expression associated to diabetes. Angiogenic changes were assessed in penile tissue of streptozotocin-induced Wistar rats, in an early (2-week) and established stage (8-week) of diabetes. Differentially expressed genes were identified by microarrays and expression data validated by quantitative real-time PCR (qrt-PCR). At protein level, quantitative immunohistochemistry confirmed the arrays data and dual immunofluorescence for selected alterations and α-smooth muscle actin (α-SMA) identified the cellular location of target proteins. The selected differentially expressed genes were also evaluated in human non-diabetic and diabetic CC by quantitative immunolabeling. At 2-week diabetes there was no differential gene expression between non-diabetic and diabetic CC. At 8-week, 10 genes were found down-regulated in diabetics. The results were validated by qrt-PCR for the insulin-like growth factor-1 (Igf1) and the natriuretic peptide receptor-1 (Npr1) genes. Dual immunofluorescence for IGF-1/ α-SMA showed predominant localization of IGF-1 in SM. NPR-1 expression was diffuse and mostly present in trabecular fibroblasts and SM. Quantitative immunostaining confirmed the decreased expression of both proteins in diabetic tissues. Concordantly, we detected a significant reduction in IGF-1 and NPR-1 protein expressions in human diabetic samples. Microarray analysis identified 10 angiogenic-related molecules deregulated in CC of established diabetes. Among them, IGF-1 and NPR-1 were significantly down-regulated and might result in preventive/therapeutic targets for ED management.

New classification of anomalous venous drainage using caverno-computed tomography in men with erectile dysfunction.

INTRODUCTION: Venous leak evaluation remains a challenge in many ED patients. Adequate anatomical evaluation may help with optimizing therapeutic strategies. AIM: Propose a new classification of venous leakage using multidetector computed tomography (MDCT) cavernography, after contrast media intracavernous injection (ICI), under pharmacological stimulation. METHODS: Thirty-eight patients gave informed consent for the study: 34 complained of ED, unsatisfied with treatment and suspected to have cavernovenous leak; four having morphological anomalies and needing surgery. Patient's clinical history, including age, vascular risk factors, penile nitric oxide release test, Doppler ultrasound and previous treatments were evaluated. MDCT consisted in: 1-ICI of 1 mL of vasoactive medications containing papaverine, chlorydrate (20 mg), urapidil chlorydrate (2.75 mg) and alprostadil (10 mcg); 2-ICI of 20-60 cc of diluted contrast media (1/3) using 20 cc of Ioprimide (300 mg/mL); 3-Spiral MDCT acquisition and three-dimensional volume rendering. MAIN OUTCOMES MEASURES: Erection degree was assessed using the erection hardness score (EHS); venous drainage was analyzed and deep, superficial veins (SVs), and caverno-spongious communications identified. MDCT findings were compared with clinical data. RESULTS: The deep dorsal vein (DDV) was opacified in 58% of patients and the SV in 50%. Cavernospongious communications were visible in 18.4%. Sixteen percent presented no visible drainage. A new classification of venous drainage anomalies is proposed: A-No visible drainage (N = 8); B-DDV and preprostatic plexus opacification (N = 11); C-Exclusive SV opacification (N = 10); D-Opacification of both SV and DDV (N = 9). All patients (with one exception) in group A quoted 4 at the EHS vs. none in the others groups (P < 0.0001, exact Fisher test). One patient in group A needed venous drainage due to prolonged erection. CONCLUSIONS: MDCT after ICI contrast media was able to differentiate between various venous pathways in men with venous origin ED, leading to a new anatomical classification. Absence of leakage was associated with normal erection under pharmacological stimulation.