Ejaculation is regulated by the coordination of somatic nerves, sympathetic nerves, and parasympathetic nerves, involving complex neurochemical interactions [6]. The sympathetic nervous system controls the internal urethral sphincter (for bladder neck closure), while the somatic nervous system regulates pelvic muscles, as well as muscles innervated by the medulla oblongata and sciatic nerve. Key brain centers involved in ejaculation include the medial preoptic area and paraventricular nucleus, both located in the hypothalamus [7].
Neuropathy is a common sequela of DM, primarily caused by chronic hyperglycemia and insulin resistance impairing the structure and function of neurons and their associated microvascular systems. Neuropathy is thought to result from oxidative stress, neuronal inflammation due to cytokine accumulation, and mitochondrial/cellular dysfunction, ultimately leading to neuronal death [8–9]. DM neuropathy is also attributed to damage to Schwann cells, which are responsible for axonal myelination and optimization of nerve transmission in the nervous system. Studies have shown that hyperglycemia in DM reduces the proliferation and migration of Schwann cells, leading to axonal dysfunction [10]. Animal studies suggest that this may be due to upregulation of phosphodiesterase type 5 in response to hyperglycemia, resulting in decreased myelin thickness and nerve conduction velocity [11].
Impaired sympathetic activation during the ejaculatory emission phase can prevent relaxation of the internal urethral sphincter/bladder neck. Human studies have also found atrophy of the internal urethral sphincter in male DM patients with RE; combined with reduced somatic nerve stimulation during ejaculation (i.e., decreased tonic contraction of the bulbospongiosus muscle), this contributes to RE in DM patients. This has been further confirmed in DM rat models [12–13].
DM patients with ED often have abnormal penile somatosensory evoked potentials and bulbospongiosus reflex latency, indicating that DM neuropathy may concurrently affect ejaculatory and penile nerves. Electrophysiological examination of penile nerves may provide reference value for determining the severity of RE and whether it is induced by DM [14].
In this study, although type 1 DM typically has an earlier onset and longer disease duration, type 2 DM patients accounted for a higher proportion. This is mainly attributed to the higher prevalence of type 2 DM in men, long-term metabolic disorders and insulin resistance, and easy neglect of microangiopathy and autonomic dysfunction—factors that increase the incidence of ejaculatory dysfunction.
The finding that many RE patients retain sexual pleasure suggests a potential functional dissociation between orgasm and ejaculatory reflex, or that some RE patients may progress to anorgasmia. The high prevalence of ED and low overall EHS in DM patients with RE indicate that sexual dysfunction in these patients is not limited to ejaculatory disorders but also involves varying degrees of erectile impairment.
Type 1 DM patients are more prone to damage to the nerve conduction and regulatory systems for sexual pleasure than type 2 DM patients, which may be related to their earlier onset age and longer disease duration. Additionally, type 1 DM patients have a significantly higher proportion of childlessness, reflecting more severe fertility impairment—possibly associated with more severe RE, extensive cumulative metabolic damage, and hypothalamic-pituitary-gonadal axis dysfunction.
Patients without sexual pleasure were older and had longer disease duration, suggesting that disease progression and aging may gradually exacerbate sexual dysfunction through cumulative neural and vascular damage. Anorgasmia in RE patients is a result of multiple factors, mainly influenced by erectile function, disease duration, and age, with blood glucose control possibly playing an auxiliary role.
Age is the main factor affecting the fertility status of RE patients, with high predictive value. Clinical evaluation should focus on EHS, age, and disease duration; constructing a multi-factor prediction model using comprehensive indicators is expected to improve the accuracy of sexual pleasure prediction, guide individualized intervention strategies, and enhance patients’ quality of life.
However, this study has limitations: the sample size is small, and the number of patients in the type 1 and type 2 DM groups is unbalanced, limiting the statistical power. Future studies should expand the sample size and include multiple centers to provide more reliable evidence for the diagnosis and treatment of DM-associated RE.
Pharmacotherapy is the mainstay of RE treatment, primarily focusing on enhancing sympathetic drive to the reproductive tract and bladder neck (e.g., pseudoephedrine) and reducing parasympathetic activity (anticholinergic drugs) to inhibit bladder neck relaxation. Intraurethral injection of collagen at the bladder neck to increase resistance against semen reflux has been reported in the literature [15]. Additionally, a human study showed that subjects treated with tadalafil for 3 months had improved ejaculatory parameters, possibly due to increased cyclic guanosine monophosphate (cGMP) levels improving external urethral sphincter relaxation and enhancing neurovascular dilation to mitigate microvascular damage to relevant nerves [16]. Currently, there are no specific drugs for RE beyond the aforementioned medications and commonly used drugs for neurotrophic support and microcirculation improvement.
Although RE has a low incidence and accounts for a small proportion of male infertility, it should not be overlooked. When pharmacotherapy is ineffective, low-frequency pulsed ultrasound therapy is an emerging alternative to assisted reproductive technology, which requires further clinical research.