Factors Involved in Sex Drive and Erection Quality: Beyond Testosterone

[Nelson Vergel]

The Complex Neurochemistry of Male Sexual Function: Understanding the Biological Foundations of Desire and Performance​

Male sexual function represents one of the most intricate orchestrations of neurochemical, hormonal, and physiological processes in human biology. Far from being a simple mechanical response, sexual desire and erectile function involve a sophisticated interplay of neurotransmitters, hormones, and biological systems that can be profoundly influenced by physical health, psychological state, and environmental factors.

The Neurochemical Symphony: Understanding the Primary Players​

The foundation of male sexual function begins with what researchers have termed the neurochemical orchestra - a complex array of hormones and neurotransmitters that work in concert to regulate attraction, arousal, and sexual behavior.

Dopamine: The Primary Driver​

Dopamine has facilitative effects on sexual motivation, copulatory proficiency, and genital reflexes. Dopamine in the nigrostriatal tract influences motor activity; in the mesolimbic tract it activates numerous motivated behaviors, including copulation; in the medial preoptic area (MPOA) it controls genital reflexes, copulatory patterns, and specifically sexual motivation.^[1,2]^


The VTA receives significant input from the MPOA, MeA, and BNST in both sexes. Numerous groups have reported elevated dopamine release in the NAc upon presentation of a potential mate and during active mating in both males and females, with escalating amount of dopamine release in a male as the mating behavioral suite progresses, with the highest release associated with ejaculation.^[3]^

Serotonin: The Natural Brake​

Serotonin (5-HT) is primarily inhibitory, although stimulation of 5-HT2C receptors increases erections and inhibits ejaculation, whereas stimulation of 5-HT1A receptors has the opposite effect. 5-HT is released in the anterior lateral hypothalamus at the time of ejaculation, and microinjections of selective serotonin reuptake inhibitors there delay the onset of copulation and delay ejaculation after copulation begins.^[4]^

Testosterone: The Foundational Hormone​

Testosterone increases nitric oxide synthase in the MPOA; nitric oxide increases basal and female-stimulated dopamine release, which in turn facilitates copulation and genital reflexes.^[1]^ Testosterone appears to be a major contributing factor to sexual motivation in male primates, including humans. The elimination of testosterone in adulthood has been shown to reduce sexual motivation in both male humans and male primates.^[5]^

Oxytocin and Vasopressin: The Bonding Chemicals​

In males, oxytocin affects the production of testosterone in the testes and makes men sexually attracted to women. In humans, it has been shown to increase trust and generosity, strengthen emotional and cognitive empathy, and reduce social anxiety and fear-related behavior. The hormones oxytocin and vasopressin are implicated in regulating both male and female sexual motivation.^[6,7]^


Oxytocin is increased in plasma during sexual activity, mainly at ejaculation, and during the manipulation of breast and genitalia, which usually happens during sexual intercourse.^[8]^

The Hypothalamic Command Center: Neural Control of Erectile Function​

The hypothalamus serves as the primary control center for sexual function, integrating signals from multiple neurochemical pathways to coordinate the complex process of penile erection. This small but crucial brain region processes inputs from dopamine, oxytocin, excitatory amino acids, melanocortins, opioids, GABA, serotonin, noradrenaline, growth hormone-releasing peptide, and nitric oxide.


The stimuli from a receptive female and/or copulation itself leads to the release of dopamine (DA) in at least three integrative hubs. The nigrostriatal system promotes somatomotor activity; the mesolimbic system subserves numerous types of motivation; and the medial preoptic area (MPOA) focuses the motivation onto specifically sexual targets, increases copulatory rate and efficiency, and coordinates genital reflexes.^[9]^

The Multifactorial Nature of Sexual Dysfunction: Health and Lifestyle Impacts​

Sexual function exists within the broader context of overall health, and numerous medical and lifestyle factors can profoundly impact the delicate neurochemical balance required for optimal sexual performance.

Obesity: A Major Risk Factor​

Obesity is a major public health issue worldwide and is frequently associated with erectile dysfunction (ED). Both conditions may share an internal pathologic environment, also known as common soil. Their main pathophysiologic processes are oxidative stress, inflammation, and insulin and leptin resistance.^[10]^


79% of men presenting erectile disorders have BMI of 25 kg/m² or greater. BMI in the range 25-30 kg/m² is associated with 1.5 times, and in the range of over 30 kg/m² with 3 times greater risk of sexual dysfunction.^[11]^


Obesity has been found to be associated with mild to moderate symptoms of erectile dysfunction, as assessed by the International Index of Erectile Function (IIEF), in the majority of studies of men with obesity.^[12]^

Diabetes and Metabolic Syndrome​

Diabetes mellitus and metabolic syndrome can affect several organ systems, resulting in the accelerated deterioration of erectile function, and can disrupt the mechanisms underpinning erections on a molecular level.^[13]^ Erectile dysfunction is common in patients with diabetes, affecting up to 50% of men.^[12]^


Low serum total testosterone predicts the development of central obesity and accumulation of intra-abdominal fat. Also, low total and free testosterone and SHBG levels are associated with an increased risk of developing the metabolic syndrome, independent of age and obesity.^[14]^

Cardiovascular Disease​

ED and CVD share common risk factors such as obesity, hypertension, metabolic syndrome, diabetes mellitus, and smoking. Moreover, they both involve underlying pathological mechanisms, including endothelial dysfunction, inflammation, and atherosclerosis. The association between ED and CVD may be attributed to the interplay among androgen levels, chronic inflammation, and CV risk factors.^[15]^


About 40% of men with ED will have hypertension, while 35% of all hypertensive men will also have ED.^[13]^

Sleep: The Critical Foundation​

Sleep represents one of the most underappreciated factors in male sexual health. Plasma testosterone levels display circadian variation, peaking during sleep, and reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with pulses every 90 min reflecting the underlying rhythm of pulsatile luteinizing hormone (LH) secretion. The increase in testosterone is sleep, rather than circadian rhythm, dependent and requires at least 3 h of sleep with a normal architecture.^[16]^


During waking hours common to both conditions, testosterone levels were lower after sleep restriction than in the rested condition (16.5 nmol/L vs 18.4 nmol/L; P = .049). The effect of restricted sleep was especially apparent between 2 PM and 10 PM.^[17]^


The findings from this study revealed that total sleep deprivation (more than or equal to 24 h) reduces the male testosterone levels, while short-term partial sleep deprivation has no significant effect on male serum testosterone.^[18]^


This study found that skipping sleep reduces a young man's testosterone levels by the same amount as aging 10 to 15 years.^[19]^

Stress and Cortisol​

When epidemiological and interventional studies are considered collectively, sleep loss and lower sleep duration are associated with lower morning, afternoon and 24-h testosterone; as well as higher afternoon, but not morning or 24-h cortisol. These reciprocal changes imbalances anabolic-catabolic signaling because testosterone and cortisol are respectively the main anabolic and catabolic signals in man.^[20]^


Sleep deprivation generates stressful stimuli intrinsically, due to circadian desynchrony and thereby increases the activation of the Hypothalamus-Pituitary Adrenal (HPA) axis, which, consequently, increases the production of corticosterone.^[21]^

Clinical Implications and Treatment Approaches​

Lifestyle Interventions​

Improved erectile function correlated significantly with the amount of weight loss and increased activity with each independently explaining about 25% of the variance of change in the IIEF score.^[22]^ Research suggests that weight loss improved erectile function in males with overweight and obesity. Weight loss could serve as an add-on therapy for ED in males with excess weight.^[23]^


Independent of BMI, physically active men (greater than 16 MET hours per week of exercise) are at 30% lower risk for ED than sedentary men. Also, increases in physical activity are independently associated with a lower risk of incident ED.^[22]^

Testosterone Therapy Considerations​

Testosterone treatment moderately improved the number of nocturnal erections, sexual thoughts and motivation, number of successful intercourse sessions, scores of erectile function. The effects of testosterone on libido were more consistent than on erectile function.^[14]^

Sleep Optimization​

Maintaining seven to eight hours of quality sleep supports optimal testosterone production, energy, sex drive, and vitality. Growth hormone, which supports tissue repair and muscle growth, is also released during deep sleep. Treating sleep apnea and improving sleep quality can often lead to noticeable improvements in sexual function and steep increases in testosterone levels.^[24]^

Conclusion​

The intricate dance of neurochemicals, hormones, and physiological processes that underlies male sexual function represents one of biology's most sophisticated regulatory systems. Understanding this complexity is crucial for both treatment and prevention of sexual dysfunction. Rather than viewing sexual problems as isolated issues, a comprehensive approach considers the entire biological, psychological, and social context of sexual health.


Effective treatment often requires addressing multiple factors simultaneously. A man experiencing erectile dysfunction may benefit not only from medications that enhance nitric oxide pathways but also from stress management techniques, cardiovascular health improvements, sleep optimization, and hormonal balance restoration.


Prevention strategies should focus on maintaining overall health and well-being, recognizing that sexual health is intimately connected to general physical and mental health. Regular exercise, stress management, adequate sleep, healthy nutrition, and avoiding excessive alcohol or drug use all contribute to maintaining the neurochemical balance necessary for optimal sexual function.


As our understanding of the neurochemical basis of sexual function continues to evolve, new therapeutic approaches may emerge that target specific aspects of this complex system. However, the fundamental principle remains clear: sexual health is best understood and addressed within the context of overall physical, mental, and relational well-being.

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References​

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