Diabetes mellitus (DM) is one of the biggest global health issues, associated with a number of microvascular complications including retinopathy, neuropathy, nephropathy, cardiovascular illnesses, and male infertility [1] . To further comprehend its function in male infertility, it is imperative to thoroughly examine how DM affects male reproductive hormones, especially testosterone. In light of these relationships, gaining knowledge about how diabetes affects male hormone balance will help manage infertility caused by diabetes and enhance treatment plans for those who are impacted.

By definition, diabetes is a set of metabolic abnormalities typified by hyperglycemia believed to be associated with aberrant insulin secretion, insulin action, or both [2] . In Africa and the Western World, diabetes is rampant and swiftly growing rapidly as a major public health issue that requires special attention. According to the International Diabetic Federation’s diabetic atlas, 366 million people worldwide were affected by diabetes in 2011, and diabetes prevalence is anticipated to rise to 552 million by 2030 [3] .

Industrial sugar use has increased significantly over the past century, mostly as a result of its widespread use in processed foods and beverages. Research shows that eating too much sugar is strongly linked to a number of health issues, including hormonal imbalances and metabolic diseases [4] . But little is known about the specific effects of industrial sugar on testosterone levels, especially in animal models.

Significant microvascular consequences linked to diabetes mellitus include male infertility, diabetic retinopathy, neuropathy, nephropathy, and cardiovascular disease [5] [6] . According to reports, type 1 and type 2 diabetes are becoming more common in young people [7] - [9] . This rise is concerning and has to be addressed right now since it could cause severe infertility problems in men who are fertile. Furthermore, research indicates that the decrease in birth and fertility rates in contemporary civilizations is closely linked to the rise in diabetes rates [10] . For this reason, researchers should not only focus on COVID therapy and vaccines, but also gross attention and grants should be given to research focused on providing remedies to cob the ugly trend of diabetes mellitus which has subtly pushed Homo sapiens into gradual extinction.

Diabetes can cause male infertility by interfering with spermatogenesis, causing degenerative and apoptotic changes in the testes, and changing glucose metabolism at the Sertoli/blood-testes barrier [1] . These changes can lead to decreased testosterone production and secretion, ejaculatory dysfunction, and decreased libido, according to a growing body of research conducted on diabetic men and animal models [11] . Numerous in vitro and preclinical investigations have focused on the biochemical pathways impacted by diabetes mellitus, which are thought to be the source of these consequences [12] . Hormonal abnormalities in the hypothalamic-pituitary-gonadal axis or direct interactions between insulin and the testes or sperm cells may be the cause of diabetes’s adverse effects on male reproductive capacity [13] [14] . It has been demonstrated that insulin replacement therapy can return sperm motility and count to normal in diabetic rat models [15] . However, insulin restores the function of the hypothalamo-hypophyseal-gonadal axis rather than directly affecting the tests to restore fertility [16] . In diabetic rats, the response to insulin treatment varies; some researchers have shown a quick recovery of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) [12] , while other studies have reported no discernible recovery of these hormones [17] [18] .

Oxidative stress may play a role in the pathogenesis of male reproductive problems associated with diabetes [19] - [21] . The Nrf2 gene is essential for the testes’ oxidative defense, and its expression decreases in diabetics [22] [23] . In addition to changes in testicular metabolite levels and spermatogenesis, men with diabetes typically have sperm with higher levels of DNA fragmentation, advanced glycation end products (AGEs), and their receptors. These factors all contribute to a decline in sperm quality and performance [19] . According to recent research, antioxidant therapy can lower associated comorbidities, enhance glycaemic management, and guard against oxidative stress brought on by free radicals [24] .

Men with diabetes frequently suffer from erectile dysfunction (ED), which is defined as the ongoing inability to obtain or sustain an erection strong enough for intercourse [25] . Compared to men without diabetes, men with type 1 or type 2 diabetes are three times more likely to experience erectile dysfunction (ED), which frequently manifests earlier in life and gets worse as the condition worsens. Since ED is primarily regarded as a vascular condition, neuropathy, vascular damage, and endothelial dysfunction are thought to be important factors, even though the precise processes behind ED in diabetes are not well understood [25] . Between 50% and 75% of men with diabetes are thought to have some form of erectile dysfunction. Endothelial dysfunction, impaired nitric oxide (NO) pathways (including downregulation of NO synthase and degeneration of nitrergic nerves), aberrant signal transduction pathways, degeneration of smooth muscle in the corpora cavernosa, and tissue remodeling are the mechanisms underlying erectile dysfunction (ED) in men with diabetes [26] . The neural NO synthase/cGMP pathway is started when sexual stimulation activates the non-adrenergic, non-cholinergic neurons. Vasodilation and increased blood flow to the corpus cavernosum result from the release of NO, which encourages the relaxation of resistant arterioles and penile cavernosal arteries. The endothelium lining of the lacunar spaces of the corpus cavernosum is stimulated by this increased blood flow, which further causes endothelial NO to be released through endothelial NO synthase [27] [28] . Penile engorgement results from these physiological and biochemical mechanisms that relax trabecular smooth muscle and cause the sinusoids in the corpora cavernosa to expand [29] . The “venoocclusive” process is the result of the expanding corpora cavernosa pressing against the tunica albuginea, which causes veno-occlusion and traps blood under pressure. Androgens control both endothelium and neural NO synthases, which are essential for this process [30] .

Furthermore, the penis’s tissue architecture depends on androgen [31] , thus, any changes or disturbances in the circulatory system, neuronal pathways, or fibroelastic characteristics of erectile tissue might affect the veno-occlusion process and lead to erectile dysfunction. Additionally, it has been demonstrated that diabetes impairs endothelium-dependent smooth muscle relaxation, which results in ED through smooth muscle failure in the penis’ microvasculature tree [32] [33] .

Therefore, examining how DM affects male reproductive hormones, especially testosterone, is crucial to comprehending its role in male infertility. Better treatment plans for individuals with diabetes and more efficient management of diabetes-induced infertility can result from an understanding of how diabetes affects men’s hormonal balance.

This research is a cross sectional analytical study aimed to comparatively study the effects of diabetes mellitus on male reproductive hormone of diabetic patients attending urology unit of Alex-Ekwueme Federal University Teaching Hospital Abakaliki. Results are presented in Figure 1 and Figure 2 and Table 1 .

The effects of industrial sugar on testosterone level of male albino rats were also studied. In this study, albino rats were grouped into 2 (control and test) of five (5) rats in each group. The test group was treated with industrial sugar via oral intubation for 21 days after which the rats were starved for 12 hours, and blood samples collected for testosterone measurement using ELISA technique. The result of this research is presented in Table 1 .

The effects of industrial sugar on weight of the albino rats were also measured and the result depicted in Figure 3 .

Male fertility is critically dependent upon normal intratesticular concentrations of testosterone to support qualitative and quantitative normal spermatogenesis. Diabetes mellitus, whether primary or unexplained, is a long-term disorder of carbohydrate, lipid, and protein metabolism characterized by glucose intolerance, hyperglycemia, and glycosuria. Great number of infertility cases have been linked to diabetes mellitus in both male and female. Neuropathy, vascular insufficiency, and hyperglycemia are believed to play a role in the pathogenesis of impotence, ejaculation disorders, and decreased libido, along with decreased vaginal lubrication and orgasm dysfunctions [34] . There has been a rise in the frequency of diabetes and use of industrial sugar among teenagers, which calls for concern since it might compromise men’s fertility during their reproductive years (foetal origin of adult disease), leading to a fall in birth rate, fertility and gradual human extinction. [35] . As a consequence, it is crucial to investigate the impact of diabetes and industrial sugar consumption on male reproductive hormone (testosterone) in male diabetic patients at the Federal University Teaching Hospital in Abakaliki, Ebonyi State, Nigeria, and in rat model.

From our studies, in Figure 1 , result showed an increased significant level of testosterone among the healthy controls and a decreased testosterone level among the diabetic groups (p < 0.05) which is consistent with the previous work by Gluud and associates [36] . They studied testosterone and androstenedione before and after 1 year of treatment in patients with newly diagnosed DM who presented with ketosis. They found significantly decreased testosterone levels prior to insulin therapy, with subsequent increase in testosterone levels 1 year later after improved control of carbohydrate metabolism. However, even with strict control of blood glucose, contradictory reports regarding the hormone levels of adult diabetics still exist.

Data available from this study suggest that diabetes mellitus and industrial sugar consumption significantly decreased the testosterone level of the volunteered male diabetic patients and in rats model compared to the controls, probably due to the alteration of conventional sperm parameters, spermatogenesis, biosynthesis of testosterone and induction of degenerative changes in the testis and epididymis, ejaculatory dysfunction and impairment of fertility in male diabetic patients as well as in experimental diabetic animals. The above-mentioned mechanisms have been proposed to explain these effects.

The study does not include the seminalysis data of the subjects (both tests and controls), because participants while consented to blood sample collection, did not give consent for collection of semen samples. Semen microscopy, culture and sensitivity would have been necessary as high blood glucose could harbor bacterial growth which may distort testicular function.

Not applicable.