Neurogenic Erectile Dysfunction

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Abstract: Erectile Dysfunction (ED) is the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance, causing tremendous effects on both patients and their partners. The pathophysiology of ED remains a labyrinth. The underlying mechanisms of ED may be vasculogenic, neurogenic, anatomical, hormonal, drug-induced, and/or psychogenic. Neurogenic ED consists of a large cohort of ED, accounting for about 10% to 19% of all cases. Its diversity does not allow an in-depth clarification of all the underlying mechanisms nor a “one size fits all” therapeutical approach. In this review, we focus on neurogenic causes of ED, trying to elucidate the mechanisms that lie beneath it and how we manage these patients.




1. Introduction

Erectile dysfunction (ED) is defined as the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance [1]. Besides the obvious, it has tremendous effects on the patient’s psychosocial health, and it affects not only their quality of life but the lives of their partners [2].

The pathophysiology of ED remains a labyrinth since many pathways can co-exist, thus contributing negatively.

Traditionally ED was divided into three large cohorts, organic, psychogenic, and of mixed etiology, but, in most cases, ED is associated with more than one pathophysiological factor, and there is always a psychological component, if not at the beginning, then at least afterward. Therefore, the most politically correct terms should be the primary organic and primary psychogenic.

The pathophysiology of ED may be vasculogenic, neurogenic, anatomical, hormonal, drug-induced and/or psychogenic.

Neurogenic Sexual dysfunction (NSD) has a prevalence of between 10% and 19% of all causes of erectile dysfunction (ED) [3]. Several reasons may influence ED in patients suffering from neurological diseases, depending on the genesis, which can be central, peripheral, or both. It appears that many neurogenic conditions have overlapping characteristics, For example, patients with diabetes mellitus (DM) may have a vasculogenic and a neurogenic component, therefore the following Table 1 must be used only for diagnostic classification purposes.

Patients experiencing neurogenic ED are a multifaceted group, making management a real challenge. In this narrative review, we focus on neurogenic causes of ED, trying to elucidate the pathophysiological mechanisms that lie beneath this and how we manage these patients, providing a compensatory navigating guide for everyday practice.




2. Physiology of Erection

The sexual response consists of a neuro-vascular event under neuro-hormonal control. Its control is orchestrated by several centers in the brain and the spinal cord. Brain centers are located in the hypothalamus and the midbrain, while two others are located in the spinal cord (sympathetic and parasympathetic autonomous nervous system). The close collaboration of all these centers guarantees a proper sexual response.

Sexual stimuli received via our senses, such as touch, vision, hearing, and smell, gather in the temple lobe and, via the amygdala, stimulate the upper centers of the hypothalamus. The main involved nuclei are the paraventricular nucleus, medial preoptic area, paragigantocellular nucleus, and locus coeruleus. Those centers are triggered not only by the stimuli mentioned above but also by the recollection of previous sexual memories, experiences, and fantasies. The neuronal signal travels to the lower centers of erection, located in the spinal cord: the psychogenic thoracolumbar-sympathetic center (Th11,12–L2,3 level) [4] and the reflexogenic sacral parasympathetic center (S2–S4 level) [5]. Additional afferent signals via the pudental nerve provoke the voluntary contraction of the bulba-cavernosum and cavernosum muscles. Both these muscles, by contracting, compress the crura of the corpa cavernosa over the pubic symphysis, thus increasing pressure inside, leading to a rigid penis.

The two centers of the spinal cord are under the control of the brain [6]. Depending on the origin of its induction and the erection center mainly involved, two types of erection can be recognized, reflective and psychogenic. On the one hand, we have a reflective erection, which is the outcome of somato-aesthetic stimulation and may be independent of sexual arousal. This is facilitated through the reflexogenic, parasympathetic erection center. On the other hand, the psychogenic erection, which predominates in humans, is generated by sexual desire driven by images, fantasies, and thoughts related to previous sexual experiences. The psychogenic, sympathetic erection center is mainly responsible for this kind of erection.

Depending on the level of injury (SCI, MS, stroke, etc.) and the severity (whether the injury is complete or not), various effects on erectile function can be demonstrated.




3. Etiology of Neurogenic ED

3.1. Central Nervous System (CNS) Conditions
3.1.1. Spinal Cord Injury (SCI)
3.1.2. Multiple Sclerosis (MS)
3.1.3. Parkinson’s Disease (PD)
3.1.4. Multiple System Atrophy (MSA)
3.1.5. Cerebrovascular Accident (CVA/Stroke)

3.2. Peripheral Neurological Impairment




4. Diagnostic Evaluation




5. Management of Neurogenic Erectile Dysfunction

5.1. Oral Pharmacotherapy

5.1.1. Phosphodiesterase Type 5 Inhibitors (PDE5Is)
5.1.2. Fampridine
5.1.3. Apomorphine

5.2. Local Therapies
5.2.1. Topical/Intraurethral Alprostadil
5.2.2. Vacuum Devices
5.2.3. Intra-Cavernous Injections
5.2.4. Low-Intensity Extra-Corporeal Shock Waves Treatment (LI-ESWT)

5.3. Regenerative Therapeutic Strategies

5.4. Penile Prostheses





6. Conclusions

Neurogenic ED is characterized by tremendous diversity since it has many etiological factors. This diversity makes it impossible to fully understand the underlying mechanisms of its pathophysiology, let alone to design a “one fits all” method of treatment. Several studies are needed, not only to elucidate the reason why ED is established in several neurological conditions but also to identify the pathways that are involved in different conditions, how they intersect and, finally, how we can provide a “tailor-made” therapeutic approach to every one of our patients, trying to meet their needs successfully.
 

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Table 1. Etiological factors of neurogenic erectile dysfunction (ED).
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Table 2. Minimal diagnostic evaluation in patients with ED (including neurogenic ED). Adapted from EAU Guidelines on Sexual and Reproductive Health 2020 [1]
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Figure 1. Management algorithm for ED. Adapted from EAU Guidelines on Sexual and Reproductive Health 2020 [1].
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Beyond Testosterone Book by Nelson Vergel
Again unfortunately too many are still caught up on TT/FT, estradiol, DHT, prolactin when it comes to ED/libido which is multifactorial.


*The pathophysiology of ED remains a labyrinth. The underlying mechanisms of ED may be vasculogenic, neurogenic, anatomical, hormonal, drug-induced, and/or psychogenic.


*
Neurogenic Sexual dysfunction (NSD) has a prevalence of between 10% and 19% of all causes of erectile dysfunction (ED)
 
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