Contextual approaches to the physiology and classification of erectile function, erectile dysfunction, and sexual arousal

doi:10.1016/S0149-7634(00)00022-1

Neuroscience & Biobehavioral Reviews

Volume 24, Issue 5, July 2000, Pages 541-560

https://doi.org/10.1016/S0149-7634(00)00022-1 Get rights and content

Abstract

This paper offers a reexamination of some long-held beliefs relating to the physiology of erectile function and dysfunction, including the idea that there is a singular physiology of erection. Rather, there appear to be plural neural, neurochemical, and endocrine mechanisms whose participation in erectile function depends on the behavioral context in which erection occurs. The best examples of this context-dependent physiology come from research on rats. For example, the medial amygdala is essential for noncontact erection in response to inaccessible estrous females, but not for erection during copulation. Also, androgen is necessary for touch-based and noncontact erection, but not for erection during copulation. Even the specific dopamine receptors important to erection may differ, depending on the context. If there is not a singular physiology of erection, then it follows that the physiology of erectile dysfunction may also vary from context to context. Thus, some disorders of the central nervous system may not be manifested in sleep-related erection, and therefore may be misinterpreted as “psychogenic” erectile dysfunction. This term belies the axiom that all psychological processes have a somatic basis; therefore, there can be no psychogenic dysfunction that does not involve organic processes which may respond to pharmacotherapy. A revised classification of erectile dysfunction based on this premise is offered. Finally, closer attention to erectile context may also illuminate male “sexual arousal” and its relation to “sexual motivation”. The former term has so many meanings in current usage as to impede research, especially into the physiology of sexual arousal, which depends on comparisons between animals and humans. It is proposed that attention be given to two variables: whether or not erection occurs and whether or not the context is sexual. The occurrence of penile erection within a sexual context is viewed as the only case in which sexual arousal may be inferred unambiguously.

Section snippets

Contexts for erection

My use of “context” may best be paraphrased as “stimulus complex,” and refers to the set of stimuli that comprise each organism's environment. This set would include the social, external physical, and internal physical stimuli (including circadian and other rhythms) that characterize the situation in which erection develops, with due consideration of the developmental and experiential history of the individual male.

Properties of erection vary with context

The distinctions being made among erectile contexts should not of themselves be construed as indicating that there are different “types” of erection. Pending evidence to the contrary, it is reasonable to suppose that the characteristics of human erection are similar across different contexts. However, in rats the physical and temporal features of erection clearly vary according to context, as the upper portion of Table 3 shows (modified from Ref. [105]). For example, although tumescence of the

Physiology of erection varies with context

In addition to context-dependent changes in the spatiotemporal properties of erection, the physiology of erection also varies with context (Table 3, lower portion). The foundations for this idea were laid at least 50 years ago. However, some of those foundations were flawed, and the several different contexts have usually been reduced to the reflexive–psychogenic dichotomy that, as noted above, seems to be untenable. Because the differential physiological regulation of erection in different

Implication for distinction between organic and psychogenic erectile dysfunction

If the physiology of erectile function varies significantly from one context to another, then it follows that the physiology of erectile dysfunction (ED) may also vary from context to context. This principle is receiving greater recognition, but one can find recent examples of failure to recognize it, especially in certain attempts by clinicians to determine whether instances of ED are due to “organic” or “psychogenic” causes. For decades, sleep-related erection (SRE) was the test of first

A contextual definition of sexual arousal

The recent availability of effective drug treatments for ED has made clear how much less we understand about the mediation of two other processes related to erectile function: sexual arousal and sexual motivation. (The latter term is also commonly referred to as sexual desire or libido.) Only sexual arousal will be addressed in detail here. Further on, I will make explicit why I consider it important to distinguish between sexual arousal and desire (see Section 5.3).

The concept of sexual

Conclusion

On the evidence reviewed here, it is not true that an erection is an erection is an erection. Though erections share many features, it becomes clear when one looks more closely at the erectile context that there are striking differences in the physiology of erection and even in the form and temporal patterning of erection. Because there is value in considering context for erectile function, there may also be value in viewing erectile dysfunction from a similar perspective. For example, the

Acknowledgements

Supported by NSF research grant IBN-9603917. Discussions with John Bancroft, Ross Buck, François Giuliano, Erick Janssen, James Pfaus, Raymond Rosen, Jacqueline Sachs, John Salamone and several other colleagues over the past few years helped to shape the ideas presented in this paper, in some cases despite their express disagreement. I thank Jacqueline Sachs, Raymond Rosen and an anonymous referee for their valuable suggestions on the manuscript itself.

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The Suggestive Effect of Apo A, Apo B, and Apo A/Apo B on Erectile Dysfunction
2021, Journal of Sexual Medicine
Citation Excerpt :
In addition, we performed a ROC curve analysis of ED and apolipoprotein for the high vascular risk group and the low vascular risk group, and we found that only the lipid profile of the low vascular risk group had a notable effect on ED. ED is usually divided into 3 categories: organic ED, psychogenic ED, and mixed ED.15 Among them, mixed ED undoubtedly accounts for the largest number of ED patients.16
Erectile dysfunction (ED) is closely related to coronary heart disease (CHD). Apolipoprotein (Apo) A1, Apo B, and Apo A/Apo B are known to be predictive factors for CHD. They are not yet a definite laboratory marker for the diagnosis of ED in cardiology. Therefore, we investigated the association between Apo A1, Apo B, and Apo A/Apo B, and ED.
To investigate the association between Apo A, Apo B, and Apo A/Apo B and the severity of ED.
A total of 152 ED patients and 39 healthy control participants underwent a fasting blood draw to test for Apo A, Apo B, and Apo A/Apo B and a detailed laboratory examination. The International Erectile Function Index (IIEF-5) was used to determine the severity of ED. Receiver operating characteristic (ROC) curve analysis was performed to identify the cutoff values for Apo A, Apo B, and Apo A/Apo B. Each questionnaire was completed before any diagnosis was made or treatment performed.
Several lipid profile indicators (Apo A, Apo B, Apo A/Apo B, lipoprotein (a), free fatty acids, and total cholesterol) were studied, along with several questionnaires.
In our study, the number of patients with no ED, mild ED, mild-to-moderate ED, and moderate-to-severe ED were 39 (20.4%), 58 (30.4%), 36 (18.8%), and 58 (30.4%), respectively. Apo A and Apo A/Apo B were significantly reduced in patients with more severe ED (P = .037 and P < .001, respectively), while Apo B was significantly increased in patients with more severe ED (P = .002). According to the ROC curve, Apo A/Apo B had a medium diagnostic value for risk of ED with an AUC of 0.743 (95% CI: 0.68–0.80). For moderate-to-severe ED, 3 apolipoprotein indexes, including Apo B, Apo A, and Apo A/Apo B had medium diagnostic performance with AUCs of 0.759 (95% CI: 0.66–0.84), 0.703 (95% CI: 0.60–0.79), and 0.808 (95% CI: 0.72–0.88), respectively.
Our results can inform cardiologists in the assessment of ED in patients with CHD.
This study is the first to investigate the association between apolipoprotein and ED in China. The major limitations are that our sample size was too small to have matched controls without ED for different Apo levels.
Our results showed that Apo B, Apo A, and Apo A/Apo B can be used as markers to evaluate the risk of ED and that these proteins play an important role in the etiology of ED.
Li X, Li D. The Suggestive Effect of Apo A, Apo B, and Apo A/Apo B on Erectile Dysfunction. J Sex Med 2021;18:448–456.
Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress
2018, Journal of Sexual Medicine
Non-organic erectile dysfunction (noED) at functional imaging has been related to abnormal brain activity and requires animal models for further research on the associated molecular mechanisms.
To develop a noED animal model based on chronic mild stress and investigate brain activity changes.
We used 6 weeks of chronic mild stress to induce depression. The sucrose consumption test was used to assess the hedonic state. The apomorphine test and sexual behavior test were used to select male rats with ED. Rats with depression and ED were considered to have noED. Blood oxygen level-dependent–based resting-state functional magnetic resonance imaging (fMRI) studies were conducted on these rats, and the amplitude of low-frequency fluctuations and functional connectivity were analyzed to determine brain activity changes.
The sexual behavior test and resting-state fMRI were used for outcome measures.
The induction of depression was confirmed by the sucrose consumption test. A low intromission ratio and increased mount and intromission latencies were observed in male rats with depression. No erection was observed in male rats with depression during the apomorphine test. Male rats with depression and ED were considered to have noED. The possible central pathologic mechanism shown by fMRI involved the amygdaloid body, dorsal thalamus, hypothalamus, caudate-putamen, cingulate gyrus, insular cortex, visual cortex, sensory cortex, motor cortex, and cerebellum. Similar findings have been found in humans.
The present study provided a novel noED rat model for further research on the central mechanism of noED.
The present study developed a novel noED rat model and analyzed brain activity changes based at fMRI. The observed brain activity alterations might not extend to humans.
The present study developed a novel noED rat model with brain activity alterations related to sexual arousal and erection, which will be helpful for further research involving the central mechanism of noED.
Chen G, Yang B, Chen J, et al. Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress. J Sex Med 2018;15:136–147.
ICV galanin-like peptide stimulates non-contact erections but not touch-based erections in adult, sexually experienced male rats
2017, Neuropeptides
Galanin-like peptide (GALP) is a neuropeptide transcribed only within the arcuate nucleus of the hypothalamus and is thought to be a mediator between energetics and reproductive function. Intracerebroventricular (ICV) injection of GALP is known to have effects on feeding, and to significantly increase gonadotropin releasing hormone- (GnRH-) mediated luteinizing hormone (LH) secretion. Furthermore, ICV GALP is known to stimulate fos production in the medial pre-optic area (mPOA) and to a lesser extent, the paraventricular nucleus (PVN). ICV injection of 5.0 nmol GALP profoundly stimulates male rat sexual behavior. It is not known if GALP's effects on sex behavior are due to an increase in appetitive or mechanical (erectile) aspects of male sexual behavior. To determine this, sexually experienced male rats were cannulated in the lateral ventricle and injected with 5.0 nmol GALP or vehicle. Immediately after injections, male rats were placed in an arena connected to a second arena via a tube with a fan. The second arena contained a steroid-primed female and her bedding. The male rat had olfactory but not visual or tactile contact with the female. We analyzed the amount of time the male rats spent investigating the air intake and the number of non-contact erections (NCEs) in a 30 minute test. ICV GALP significantly (p < 0.05) increased both the amount of time of olfactory investigations and NCEs compared to vehicle. In a second set of animals, we tested if ICV GALP could stimulate touch-based erections. GALP had no significant effect on touch-based erections compared to vehicle. These data suggest that GALP's activation of fos within the mPOA is indicative of its action to stimulate the appetitive aspects of male sexual behavior.
Male Sexual Behavior
2017, Hormones, Brain and Behavior: Third Edition
Copulation and the physiological mechanisms of erection and ejaculation are described. In most rodents, testosterone's behavioral effects are mediated mostly by conversion to estrogen in neurons, whereas in primates, including humans, and some other animals, testosterone itself is the major hormone. Brain areas that control mating include the amygdala, bed nucleus of the stria terminalis, medial preoptic area, paraventricular nucleus, mesolimbic and nigrostriatal tracts, central tegmental field, lateral and ventromedial hypothalamus, and motor outputs, including the spinal cord. Drugs affecting dopamine, norepinephrine, serotonin, glutamate, gamma-aminobutyric acid, opioids, nitric oxide, oxytocin, and orexin/hypocretin administered systemically or into specific brain areas influence mating.
Male sexual behavior
2016, The Curated Reference Collection in Neuroscience and Biobehavioral Psychology
Most simply, male sexual behavior entails locating a receptive female, attaining a penile erection, inserting the erect penis into the female's vagina, and ejaculating. In rodents, sensory input travels from chemosensory or genital receptors to the corticomedial amygdala, which relays it directly or indirectly to the medial preoptic area and other integrative sites. Erections and ejaculation are controlled by nuclei in the lumbosacral spinal cord, which are under supraspinal regulation. Dopamine, nitric oxide, and glutamate facilitate mating, and serotonin, gamma-aminobutyric acid (GABA), endocannabinoids and opioids generally inhibit mating, though exceptions occur. Testosterone and its metabolites, estradiol and dihydrotestosterone, are critical for male sexual behavior in most species.
Anatomy and physiology of genital organs - men
2015, Handbook of Clinical Neurology
Citation Excerpt :
In humans and animals, penile erection occurs in several contexts, some of which have no sexual content (in utero or during paradoxic sleep). It is thought that several different cerebral regions participate in erection in different contexts (Sachs, 2000). Each context may reflect the contribution of a unique combination of several brain nuclei, and one brain nucleus may participate in the occurrence of erection in several contexts.
Male sexual functions involve a number of organs and structures in genitalia whose role is to produce fertilizing gametes and to allow female-partner insemination. The testes belong to the reproductive and endocrine systems as they synthesize spermatozoa and androgens, and are under finely regulated hormonal control by the hypothalamopituitary axis. Sexual responses are controlled by a complex and coordinated interplay of both the somatic and the autonomic nervous system in multiple components of the brain, spinal cord, and relevant peripheral organs. Erectile bodies are an essential element of the penis and engorgement of the penis with blood leads to penile tumescence. Blood engorgement is due to relaxation of smooth-muscle cells of erectile tissue and endothelium of the penile arteries. The penis gains additional rigidity when the ischiocavernosus muscles contract. Stimuli from peripheral and/or central origins activate particular spinal nuclei, causing penile erection. Ejaculation consists of two phases, emission and expulsion, which correspond, respectively, to secretion of the different components of the semen by sex glands and forceful expulsion of semen due to rhythmic contractions of the bulbospongiosus muscle. A spinal generator of ejaculation integrates genital stimuli and sexual cues and, when the excitatory threshold is reached, triggers ejaculation by orchestrating the activation of autonomic and somatic pathways commanding the peripheral events of ejaculation.

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ReviewContextual approaches to the physiology and classification of erectile function, erectile dysfunction, and sexual arousal

Abstract

Section snippets

Contexts for erection

Properties of erection vary with context

Physiology of erection varies with context

Implication for distinction between organic and psychogenic erectile dysfunction

A contextual definition of sexual arousal

Conclusion

Acknowledgements

J Urol

Prog Neurobiol

J Psychosom Res

Behav Biol

Horm Behav

Physiol Behav

Physiol Behav

Physiol Behav

Horm Behav

Neurosci Biobehav Rev

Urol Clin N Am

J Auton Nerv Syst

Neuropsychologia

Horm Behav

Horm Behav

Brain Res

Horm Behav

Physiol Behav

Behav Br Res

Neurosci Lett

Pharmacol Biochem Behav

Brain Res

Horm Behav

Brain Res

Brain Res

Brain Res

Neurosci Biobehav Rev

Adv Study Behav

Horm Behav

Neurosci Biobehav Rev

Brain Res

Adv Study Behav

Brain Res

Physiol Behav

Horm Behav

Brain Res

Psychoneuroendocrinology

Appl Anim Behav Sci

Physiology of penile erection

Physiol Rev

Arousal and the causation of behaviour

Behaviour

Impotence of the male rodent after sympathetic denervation of the genital organs

Am J Physiol

Antidepressants in the treatment of premature ejaculation

J Sex Marital, Ther

Human sexuality and its problems

Animal models of human sexual behavior

Analysis of factors involved in the arousal, maintenance and manifestation of sexual excitement in male animals

Psychosom Med

The characteristics of masculine sex drive

Review
Contextual approaches to the physiology and classification of erectile function, erectile dysfunction, and sexual arousal