Impact of Immune System Activation and Vascular Impairment on Male and Female Sexual Dysfunction

Abstract

Introduction: Male and female sexual dysfunction (SD) is considered a multifactorial condition. Numerous studies have shown the involvement of inflammatory processes in this pathological condition. Sexual intercourse requires healthy and functioning vessels to supply the pelvic region in both males and females, generating penile erection and clitoral and vaginal lubrication, respectively. Cardiovascular diseases and associated risk factors may contribute negatively to pelvic blood flow, possibly through immune system activation.

Aim: The study aimed to address the correlation between vascular inflammation driven by immune system activation and SD in males and females.

Methods: A literature review was performed to identify articles addressing male and female SD and vascular inflammation. Key words included "male and female sexual dysfunction," "vascular inflammation," "iliac and pudendal arteries dysfunction," "genitourinary tract," and "blood flow."

Main outcome measures: Management of systemic and local inflammation may be a useful alternative to improve SD and reduce the risk of cardiovascular diseases in the future.

Results: Increased levels of cytokines and chemokines have been detected in humans and animals with hypertension, obesity, and diabetic conditions. Chronic activation of the innate immune system, especially by pathogen- or damage-associated molecular patterns, and metabolic-related disorders may act as triggers further contributing to an increased inflammatory condition. Due to the reduced size of vessels, SD and retinal vascular impairments have been shown to be predictive factors for cardiovascular diseases. Therefore, considering that blood flow to the genitalia is essential for sexual function, endothelial dysfunction and vascular remodeling, secondary to chronic immune system activation, may be implicated in male and female vasculogenic SD.

Conclusions: Several conditions appear to play a role in SD. In the present review, we have identified a role for the immune system in generating vascular and tissue impairments contributing to erectile dysfunction and female SD. Calmasini FB, Klee N, Webb RC, et al. Impact of Immune System Activation and Vascular Impairment on Male and Female Sexual Dysfunction. Sex Med Rev 2019;7:604-613.

Keywords: Cardiovascular diseases; Endothelial dysfunction; Erectile dysfunction; Female sexual dysfunction; Innate immune system; Vascular inflammation.

Figure 1.

Mechanisms of vascular change in sexual dysfunction. Initiating factors that contribute to sexual dysfunction in both sexes include: age, physical inactivity, obesity, diabetes, hypertension, stress and anxiety, toxins and infectious agents. These initiating factors may lead to resulting events that end in a final common pathway of vascular dysfunction.

Figure 2.

Toll-like receptor signaling – general features of the canonical pathway. The myeloid differentiation primary response 88 (MyD88) is an innate immune signal transduction adaptor common for almost all TLR (except for the TLR3), which recruits interleukin 1 receptor-associated kinase (IRAK). The IRAK interacts with adapter protein tumor necrosis factor-associated factor 6 (TRAF6), leading to nuclear factor kappa light chain enhancer of activated B cells (NF-kB) translocation to the cellular nuclei. The TLRMyD88 signaling pathway results in increased pro-inflammatory cytokines and interferon production.

Figure 3.

Damage-associated molecular patterns (DAMPs) and vascular inflammation. DAMPs are released or secreted from dying or senescent cells, respectively. Once released, the DAMPs bind to TLRs leading to the production of reactive oxygen species and pro-inflammatory cytokines. These latter molecules act on the vasculature to cause inflammation and may contribute to penile or clitoral dysfunction.