It is well known that ED can result from pre-existing hormone and metabolic impairments. At the opposite, ED can be an early marker of latent endocrine disorders. If this correlation has been established for DM, no data are available for other endocrine disorders, potentially associated with ED. In order to increase the convincing evidence for performing hormonal investigation in men with sexual dysfunction, we studied the prevalence of a previously unknown glycemic and endocrine disorder, in a population of patients with ED.
In this study, in 30% of subjects affected by ED, a new diagnosis of a previously unknown endocrine disorder was carried out. Hypogonadism was the most frequent hormonal alteration in the group of subjects with new diagnosis of endocrine/metabolic disorders. This is not surprising, since androgens play a central role in enhancing sexual desire and maintaining adequate sleep-related erections [5, 9]. Again, testosterone modulates nearly every component involved in erectile function, including pelvic ganglions, smooth muscle as well as endothelial cells of the corpora cavernosa [6, 22]. In this study, elevated estradiol levels were also observed in some patients affected by hypogonadism. It has been hypothesized that high level of estradiol might reduce NO-mediated cavernosal smooth muscle relaxation and intracavernosal pressure, worsening the erectile function [23].
Interestingly, we observed that the most frequent alteration in the group of subjects with known pathology was DM, differently from the group of subjects with new diagnosis. This could be explained by the fact that more frequently an occasional finding of hyperglycemia can occur during routine examinations. In addition, diabetes can manifest itself through different signs and symptoms before the diagnosis of ED. On the other hand, the SUBITO-DE study highlighted a high prevalence of ED, hypogonadism and depressive symptoms among male patients with newly diagnosed T2DM [24]. On this matter, psychological factors are strictly related to ED and are seldom investigated also in DM patients [25]. Furthermore, some comorbidities closely associated with diabetes as well as DM complication, such as obesity, hypertension and its pharmacological treatments, atherosclerosis, neuropathy, nephropathy, as well as infections, disease of penile structure and depression could be considered as co-factors for ED [10, 26]. This evidence is confirmed by the fact that metabolic disorders are associated with reduced T levels, arteriogenic ED and higher risk of major adverse cardiovascular events [6, 23, 27]. To this regard, Corona et al. [14] showed a higher risk of severe ED and pathological penile Doppler ultrasound parameters in patients with DM, both established and newly diagnosed, as well as impaired fasting glucose.
However, also the prevalence of newly diagnosed glycemic disorders in the present population is fairly high (17.3%). In this study, men with DM represents the group with the most severe form of ED, considering the difficulty in the achievement of erection and the absence of spontaneous erection. In fact, the severity of ED increases with the duration of diabetes, poor glycemic control and presence of microvascular complications [11], and diabetes treatment as well as educational therapy and lifestyle change should be suggested [28, 29]. However, the logistic regression analysis showed that, along with the new diagnosis of DM, hypertension and age worsen the severity of ED, but not BMI. In this regard, a recent study conducted by Yuan et al. highlighted that DM showed a direct causal effect on ED, independent of obesity and dyslipidemia [30].
A number of epidemiological data support the relationship between sexual function and testosterone levels as well as glycemic disorders [31, 32]. To this regard, Maseroli et al. showed that DM, hypogonadism and hyperprolactinemia are more frequent in subject consulting for ED compared to general population of the same geographic area [31]. However, several other hormones are also involved in sexual functioning and should be investigated in a proper work-out of ED [32]. Considering thyroid function, in this study an alteration was assess in 12.3% of cases. These data are partially in agreement with Gabrielson et al. who reported a prevalence estimated in selected populations of sexual dysfunction of about 60% in patients with hypothyroidism and hyperthyroidism [33]. In the present study, a subclinical hyperthyroidism was mainly diagnosed. Similarly, Chen et al. [34] observed an increased prevalence of ED in patients with subclinical hypothyroidism compared to patients with euthyroidism, and they recommended screening for thyroid dysfunction in men with ED. Even if hyperthyroidism was mainly associated with acquired premature ejaculation [35], in this study most of the thyroid dysfunction was related to hyperthyroidism or subclinical hyperthyroidism (10% and 55%, respectively), compared to overt hypothyroidism or subclinical hypothyroidism (10% and 24%, respectively). This suggests the need to better investigate this topic.
The prevalence of hyperprolactinemia in the present study was 11.5%. In men consulting for sexual dysfunction, hypoprolactinemia and hyperprolactinemia have been evaluated [36, 37]. However, while the association between hyperprolactinemia and hypoactive sexual desire is well defined, more studies are needed to completely understand the role of these hormones in regulating male sexual functioning. Furthermore, erectile dysfunction in association with high prolactin levels is frequent in patients suffering from psychiatric disorders and taking psychotropic drugs [38, 39]. To this regard, in this study psychiatric patients were excluded.
Finally, almost half of the patients with new diagnosis of endocrine or glycemic disorders previously used PDE5-i. This can cause a significant number of delay or missed diagnoses of the disease which caused this symptom [15].
The main limitation in this study is its retrospective nature and the absence of psychological assessment and psychometric test. Furthermore, we only included hormonal and glycemic alteration diagnosed by routine screening, therefore adrenal, parathyroid and other pituitary dysfunctions were not considered. However, no definite evidence of these last hormones, as well as for dihydrotestosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, are available in the management of ED [32].
In conclusion, to screen endocrine disorders is very useful in the diagnostic-therapeutic management of ED patients, because it allows to define the diagnosis and establish an etiopathogenetic treatment in a large number of patients. As most endocrine causes of ED are treatable, every effort should be made to exclude potential hormonal and metabolic etiologies underlying ED at an early stage. Finally, it is still more relevant to early detect DM as it is associated with ED severity, especially in elderly man and in presence of hypertension.