Menoufia Medical Journal

ORIGINAL ARTICLE
Year
: 2018  |  Volume : 31  |  Issue : 3  |  Page : 922--927

A Study of hypogonadism in type 2 Diabetes Mellitus male patients attending Shebin ElKoum Teaching Hospital- Egypt


Mostafa G El-Nagar1, Alaa El-Din A Daood1, Mohamed Z Nouh1, Ahmed M Essa2,  
1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Internal Medicine, Ministry of Health, Tanta City, Egypt

Correspondence Address:
Ahmed M Essa
3-Omar Makrm Street, Tanta City, El-Gharbia governorate
Egypt

Abstract

Objective To the objective of this article is to evaluate serum-free testosterone levels as an indicator of hypogonadism in male patients with type 2 diabetes mellitus (DM). Background DM is considered to be one of the most common chronic diseases. Male hypogonadism is characterized by low levels of serum testosterone and is closely linked to the development of diabetes. Patients and methods This study included 80 individuals recruited from the Internal Medicine Department of Shebin El-Kom Teaching Hospital, Menoufia, Egypt. They were classified into: a case group which included 40 patients of type 2 DM in the age group of 30–65 years and a control group which included 40 healthy control persons matched for age and sex. After providing written informed consent, all patients were clinically evaluated, had routine laboratory investigations and assessment of glycated hemoglobin% (HbA1c%) and free testosterone and those who had low levels of free testosterone underwent assessment of the circulating levels of the follicle-stimulating hormone and luteinizing hormone. Results There was significant difference between the two groups regarding the presence of erectile dysfunction and hypogonadism as their percentages were increased in the case group. A comparison between diabetic patients with hypogonadism and diabetic patients with eugonadism regarding HbA1c has shown that diabetic patients with hypogonadism had significant elevated levels of HbA1c. Conclusion This study demonstrates the presence of a significant relationship between type 2 DM and presence of hypogonadism and erectile dysfunction in men.



How to cite this article:
El-Nagar MG, Daood ADA, Nouh MZ, Essa AM. A Study of hypogonadism in type 2 Diabetes Mellitus male patients attending Shebin ElKoum Teaching Hospital- Egypt.Menoufia Med J 2018;31:922-927


How to cite this URL:
El-Nagar MG, Daood ADA, Nouh MZ, Essa AM. A Study of hypogonadism in type 2 Diabetes Mellitus male patients attending Shebin ElKoum Teaching Hospital- Egypt. Menoufia Med J [serial online] 2018 [cited 2019 Jul 18 ];31:922-927
Available from: http://www.mmj.eg.net/text.asp?2018/31/3/922/248717


Full Text



 Introduction



Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels[1]. It starts in the middle or older age, although the numbers of type 2 diabetics are increasing in young people[2].

DM type 2 can lead to the damage of many organs throughout the body. In addition to chronic complications, DM is related to hypogonadism, nonalcoholic fatty liver disease, osteoporosis, and cancer. Hypogonadism in men seriously affects the life quality in diabetic patients[3].

Hypogonadism in men is a common disease accompanied by several clinical features and low levels of serum-free testosterone. It's typical clinical manifestations include loss of memory, physical decline, difficulty in concentration, depression, low libido, and erectile dysfunction (ED). It significantly affects patients' quality of life[4].

Decreases in free testosterone levels can lead to different degrees of pathophysiological changes in the bone, muscle, fat, and the cardiovascular system[5]. It has been found that hypogonadism in men is caused by a variety of chronic illness[6].

In the recent time, it has been shown that hypogonadism is closely related to the development of diabetes[7]. It has been confirmed that male type 2 diabetic patients are significantly more likely to have hypogonadism: the percentage of diabetic patients with low total testosterone levels are 36.5%[8].

 Patients and Methods



Approval by the Hospital Ethics Committee, and written informed patient consent with an explanation regarding the purpose, methods, effects, and complications were taken to all enrolled patients. This study included 80 individuals who were recruited from the Internal Medicine Department of Shebin El-Kom Teaching Hospital, Menoufia, Egypt. The study was done during the period from November 2015 to 1 November 2016.

This study included 80 patients who were classified into two groups:

Case group: this group included 40 male patients with type 2 DMControl group: this group included 40 healthy men.

All patients were clinically evaluated, had routine laboratory investigations and assessment of glycated hemoglobin (HbA1c) (Beckman Coulter Inc., Brea, California, USA) and free testosterone (Free Testosterone ELISA; IBL International GmbH, Hamburg, Germany) and those who had low levels of free testosterone underwent assessment of the circulating levels of follicle-stimulating hormone (FSH) (FSH ELISA; PishtazTeb Diagnostics, European authorized representative: JTC Diagnosemittel UG, Schulweg, Voehl, Germany) and luteinizing hormone (LH) (LH ELISA, PishtazTeb Diagnostics, European authorized representative, JTC Diagnosemittel UG).

Statistical analysis

All data were collected, tabulated, and statistically analyzed using SPSS 19.0 for Windows (SPSS Inc., Chicago, Illinois, USA) and MedCalc 13 for Windows (MedCalc Software BVBA, Ostend, Belgium). Data were expressed as mean ± SD; t-test was used to assess the difference between the studied parameters in the two groups. The frequencies were expressed in percentage. χ2-test was used to assess the difference between the studied frequencies in the two groups. Correlation coefficient (r) was used to evaluate the relation between the studied parameters in the same group. P value was considered significant if less than 0.05 and highly significant if less than 0.001[9].

 Results



Concerning baseline clinical characteristics there was no significant difference between the two groups as regards age, waist circumference, and BMI (P > 0.05). Regarding laboratory findings there was significant difference between the two groups regarding HbA1c and free testosterone (P < 0.05) [Table 1]. There was significant difference between the two group regarding the presence of ED and hypogonadism as their frequencies were increased in the case group (P < 0.05) [Table 2] and [Figure 1].{Table 1}{Table 2}{Figure 1}

Comparison between diabetic patients with hypogonadism and eugonadism regarding baseline clinical characteristics has shown no significant difference between the two groups regarding age, waist circumference, BMI, and duration of DM (P > 0.05). Comparison between diabetic patients with hypogonadism and eugonadism regarding HbA1c has shown significant difference between the two groups (P < 0.05) [Table 3],[Table 4],[Table 5],[Table 6] and [Figure 2].{Table 3}{Table 4}{Table 5}{Table 6}{Figure 2}

Comparison between patients with hypogonadism in the two groups regarding the level of FSH and LH has shown significant differences between the two groups as regards FSH; however, there was no difference between the two groups as regards LH [Table 7].{Table 7}

The correlation study showed no significant correlation between serum-free testosterone and age, BMI, and waist circumference. However, there was an inverse significant correlation between serum-free testosterone and the duration of diabetes and HbA1c [Figure 3] and [Figure 4].{Figure 3}{Figure 4}

 Discussion



There was significant difference between the two groups regarding free testosterone (P = 0.0005). The same results were obtained by Almihy et al.[10] in a study which included 40 male patients with type 2 DM; they explained that the difference in free testosterone level between diabetic patients and control group such as the low testosterone levels cannot be explained only by the lower levels of sex hormone-binding globulin associated with insulin resistance. It has been demonstrated that free testosterone levels, which are independent of sex hormone-binding globulin, are low in one-third of diabetic men[11].

There was significant difference between the two groups regarding the presence of hypogonadism as 25% of patients in the case group had hypogonadism compared with 7.5% of individuals in the control group. A cross-sectional study of 1089 patients with type 2 diabetes demonstrated that 36.5% of diabetic patients exhibit hypogonadism[8]. A recent study in Egypt by Ghazy et al.[12] found that 33% of men with type 2 DM had hypogonadism. These differences may be due to difference in the age of patients, duration of DM, presence of complications, as well as due to the difference in the cut-off points used for testosterone[13].

There was significant difference between the two groups regarding the presence of ED as their percentages were increased in the case group. Epidemiological study has reported that 75% of men with type 2 DM has sexual dysfunction, particularly ED[14].

Comparison between diabetic patients with ED regarding baseline clinical characteristics showed no significant difference between the two groups regarding waist circumference and BMI. This is in accordance with previous study which reported no correlation between ED and BMI[15].

Comparison between diabetic patients with ED regarding hypogonadism showed that hypogonadism was significantly increased among diabetic patients with ED. Ghazy et al.[12] found that hypogonadism was more prevalent among diabetic patients with ED versus 61.0% of the eugonadal patients.

This highlights the importance of low serum testosterone, and consequently hypogonadism in the pathogenesis of sexual dysfunction in men having type 2 DM rather than incriminating diabetic autonomic neuropathy as the main and sole pathogenetic factor. Raising the awareness about this will consequently provide patients with type 2 DM wider therapeutic approach that would definitely improve the outcomes[13].

However, there was significant difference between the two groups regarding the duration of DM as the duration was increased in patients with ED. Longer duration of DM and poorer glycemic control in diabetic men has been reported by some studies previously as the predictors of ED in DM[16],[17]. Lu et al.[18] in a study concluded that younger men with type 2 DM probably give more benefits of better glycemic control rather than older diabetic men to reduce the prevalence of ED.

Comparison between patients with hypogonadism and those with eugonadism in the case group regarding HbA1c showed significant difference as HbA1c is elevated among diabetic patients with hypogonadism. This can be explained as chronic hyperglycemia could inhibit the hypothalamic–pituitary–testicular axis[19].

A positive relationship has been found between hypogonadism and overweight or obesity[20]. Our study demonstrated that diabetic patients with hypogonadism have elevated BMI and increased waist circumference when compared with diabetic patients with eugonadism although this difference is still nonsignificant. A possible explanation for the significant effect of BMI on hypogonadism in men with type 2 diabetes might be that the transformation of testosterone into estrogen by aromatase results in a decrease in testosterone levels[21].

To clarify if the type of hypogonadal state was due to a hypothalamic–pituitary–gonadal axis or due to a pure gonadal defect, the levels of FSH and LH had been also assessed. In the current study a comparison between patients with hypogonadism in case and control groups has shown significant difference between the two groups as regards FSH; however, there was no significant difference between the two groups as regards LH. These results would consider a state of hypogonadotropic hypogonadism, which is mostly functional secondary to a chronic disease such as type 2 DM[13].

Obesity and insulin resistance conditions that are commonly associated with type 2 DM could be associated with impaired function of hypothalamic–pituitary–testicular axis[11]. Increased level of tumor necrosis factor α and interleukin 1B in obesity was found to reduce hypothalamic gonadotropin-releasing hormone and LH secretion in an animal study[22].

The reports on the levels of gonadotropic hormones in men with type 2 DM are conflicting. Dandona and Dhindsa[23] found that 25 and 4% of men with type 2 DM had hypogonadotropic and hypergonadotropic hypogonadism, respectively. Onah et al.[24] reported higher FSH and LH in type 2 DM. Ando et al.[25] reported normal FSH and LH in type 2 DM. However, Hussien and Al-Qatsi[26] reported low levels of FSH and LH.

There was significant indirect correlation between the serum levels of free testosterone in the case group and the duration of diabetes. This result is in accordance with other research[8].

Also, there was significant indirect correlation between the serum level of free testosterone in the case group and HbA1c. This result is in agreement with the findings of Kapoor et al.[27], while it is in contrast with the results obtained by Grossmann[28]. Our findings also contradict those of the study undertaken by Fukui et al.[29] in which total testosterone concentrations correlated positively with HbA1c concentrations.

There was no significant correlation between serum level of free testosterone and BMI. This is in accordance with a study that reported no relationship between total testosterone and BMI[30].

 Conclusion



In conclusion, we found that a significant number of men with type 2 DM have testosterone insufficiency and hypogonadism. Diagnosis of hypogonadism is difficult in that the symptoms are nonspecific, especially in diabetic men, and this explains the importance of free testosterone measurement to diagnose hypogonadism in these patients. Also, this study demonstrates that ED prevalence is high in men with type 2 DM and is associated with the duration of DM and levels of free testosterone.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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