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ORIGINAL ARTICLE Table of Contents  
Ahead of print publication
Frequency and determinants of hypogonadism and erectile dysfunction in men with newly detected type 2 diabetes


1 Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
2 Department of Biochemistry, Medical College for Women and Hospital, Dhaka, Bangladesh
3 Department of Epidemiology and Biostatistics, Institute of Child and Mother Health, Matuail, Dhaka, Bangladesh
4 Department of Cardiac Surgery, National Institute of Cardiovascular Diseases, Dhaka, Bangladesh

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Date of Submission28-Apr-2022
Date of Decision01-May-2022
Date of Acceptance05-May-2022
Date of Web Publication20-Jul-2022
 

  Abstract 


Introduction: Hypogonadism in males is characterized by low serum testosterone (T) levels together with clinical symptoms and is more common in diabetes mellitus (DM). Association between DM and hypogonadism has been studied in different populations but is not clearly known in Bangladeshi population. Objectives: The objective of this study was to find out the frequency and determinants of hypogonadism and erectile dysfunction (ED) in men with newly detected type 2 DM diabetes (T2DM). Materials and Methods: A cross-sectional study encompassing 1940 newly T2DM male patients (age: 42.57 ± 7.4 years; body mass index [kg/m2]: 26 ± 5.1; mean ± standard deviation) was carried out in the Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, to see hypogonadism. Measurement of serum total testosterone (TT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), and follicle stimulation hormone (FSH) was measured by chemiluminescent technology. Results: Among hypogonadal subjects, according to calculated Free Testosterone (cFT) and Androgen Deficiency in the Aging Male (ADAM) criteria, the frequency of hypogonadotropic hypogonadism was 80% which, on the basis of TT and ADAM criteria, was 92.5%. There was no significant difference for hypogonadism among either the hemoglobin A1c (HbA1c) categories (P = 0.23) or age groups (P = 0.9). Hypogonadal and eugonadal groups significantly differed both according to TT and ADAM (81.5% vs. 43.4%, P = 0.01) and cFT and ADAM (93.3% vs. 47.7%, P ≤ 0.001) criteria for ED. There was a significant difference between the groups for SHBG (21.7 ± 11.6 vs. 30.71 ± 22, P = 0.05) by TT and ADAM criteria. Similarly, cFT and ADAM criteria also revealed a statistically significant difference for SHBG (38.04 ± 19.90 vs. 25.28 ± 19.37 nmol/l, P = 0.03) and total cholesterol (211.40 ± 44.7 vs. 191.3 ± 32.64 mg/dl, P = 0.04). However, in both the groups, LH, follicle-stimulating hormone (FSH), HbA1c, fasting blood sugar, 2 h after 75 g glucose, triglyceride, high-density lipoprotein, and low-density lipoprotein did not differ significantly. cFT significantly correlated with age (r = ‒0.3503, P = 001) and SHBG (r = ‒0.37, P ≤ 0.01) whereas TT with SHBG (r = 0.58, P = 0.01). By multiple regression, ED and SHBG were significant predictors for hypogonadism (P = 0.01 and 0.03, respectively). Conclusion: It was concluded that a significant number of newly detected male T2DM subjects have symptoms of hypogonadism judged on the basis of TT, cFT, and ADAM scores. Poor glycemic control may affect gonadal and erectile functions. This aspect should be considered while diagnosing male subjects as T2DM.

Keywords: Erectile dysfunction, hypogonadism, type 2 diabetes mellitus


How to cite this URL:
Selim S, Lona H, Imran S, Rahman M, Mahjabeen S, Mustari M. Frequency and determinants of hypogonadism and erectile dysfunction in men with newly detected type 2 diabetes. Bangladesh J Endocrinol Metab [Epub ahead of print] [cited 2022 Aug 10]. Available from: http://www.bjem.org/preprintarticle.asp?id=351526





  Introduction Top


Diabetes mellitus (DM) is a condition of impaired carbohydrate metabolism caused by either lack of insulin secretion or decreased sensitivity of the tissue to insulin. It is one of the most common metabolic disorders that are characterized by hyperglycemia and other signs, and its incidence is rapidly increasing all over the world.[1] Asian population tends to develop diabetes at younger ages and at lower body mass index (BMI) levels than Caucasians and other ethnic groups. Several factors contribute to accelerated diabetes epidemic in Asians, including the “normal-weight metabolically obese” phenotype, high prevalence of smoking and heavy alcohol use, high intake of refined carbohydrates (e.g., white rice), and dramatically decreased physical activity levels.[2] Another study found the prevalence of DM and glucose intolerance to be high among the adult population of Bangladesh; around 10% and 23% of the study participants had diabetes and prediabetes, respectively. Testosterone deficiency (TD) is defined as low serum testosterone levels in a symptomatinc adult male.[3] There are several mechanisms for the association of low serum testosterone level and type 2 DM (T2DM) with insulin resistance and obesity as central features. To date, mechanisms underlying the association between T2DM and hypogonadism are unclear though various hypotheses involving abnormal regulation of hypothalamic–pituitary‒gonadal axis at various levels, impaired Leydig cell steroidogenesis, dysglycemia, increased fatty acid, hyperinsulinemia, and leptin have been proposed.[4],[5],[6] Although the clinical significance of hypogonadism in adult men is becoming increasingly recognized, the extent of its prevalence in the general population is underappreciated. A large number of men with hypogonadism remain undiagnosed and untreated.[7] Hypogonadism is characterized by low serum testosterone (T) levels together with clinical symptoms of postpubertal hypogonadism that include (1) sexual dysfunction, such as reduced libido, erectile dysfunction (ED), diminished penile sensation, difficulty attaining orgasm, as well as reduced ejaculate with orgasm; (2) reduced energy, vitality, or stamina; (3) depressed mood or diminished sense of well-being; (4) increased irritability; (5) difficulty concentrating and other cognitive problems; and/or (6) hot flushes in some cases of acute onset. Signs of hypogonadism include (1) anemia, (2) muscle wasting (sarcopenia), (3) reduced bone mass or bone mineral density, (4) the absence or regression of secondary sex characteristics, (5) abdominal adiposity (i.e., “potbelly” obesity), and/or (6) oligospermia or azoospermia.[8] Despite high prevalence of diabetes, there is a paucity of literature regarding hypogonadism in newly detected diabetes in men in Bangladesh, and hence, clinical and biochemical assessment of hypogonadism in early stage of T2DM is pertinent. The objectives of this study were to determine the frequency and determinants of hypogonadism and ED in men with newly detected T2DM and to find out the relationship between testosterone levels with BMI, lipid profile, and glycemia.


  Materials and Methods Top


This was a cross-sectional observational study. Adult male patients attending the Endocrinology Outpatient Department (OPD), Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, with diagnosis of newly detected T2DM were approached to participate in the study following inclusion criteria from April 2021 to January 2022. A total of 1940 newly detected T2DM adult male patients have been recruited in the study. The patients possessing any of the following characteristics were excluded from this study; receiving testosterone replacement therapy in any form, on treatment for gonadal functions, any surgical interventions to gonads or anti-retroviral therapy for HIV-AIDS.

The study obtained ethical clearance from Bangladesh Medical Research Council.

Study procedure

Demographic and anthropometric measures as well as other information of all study subjects were recorded in the pretested data collection sheet (ANEX-III). Fasting morning (8–10 Am) blood samples (5 ml) for hormonal assay were collected from each subject in a clot activator. Vacutainer tubes were kept vertically at room temparature for 15-20 minutes. Serum was separated by centrifugation (around 8000 rpm) at room temperature, and serum of each patient was transferred to two Eppendorf tubes after labeling and preserved at ‒20°C until further analysis. Measurements of hormonal assay for serum total testosterone (TT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), FSH, and albumin were performed. Hormonal assay was performed in the Department of Laboratory Medicine, BSMMU. Sociodemographic variables of the respondents were recorded by face-to-face interview using the semi-structured questionnaire. Androgen Deficiency in Aging Males (ADAM) questionnaire was used to evaluate the clinical symptoms of androgen deficiency. Their anthropometric measures including height, weight, waist circumference (WC), hip circumference (HC), and blood pressure were recorded. After obtaining informed consent, fasting morning serum testosterone, LH, FSH, SHBG, lipid profile, and hemoglobin A1c (HbA1c) were measured. Collected data were entered and edited; the error was identified and minimized. All data were processed by using SPSS program version 23, SPSS for Windows, Version 16.0. Chicago, SPSS Inc.

Operational definitions

Male hypogonadism

Male hypogonadism is a clinical syndrome resulting from insufficient levels of serum testosterone.[9]

cFT

As reference laboratory methods for measuring free testosterone (FT) by equilibrium dialysis (ED) are laborious, costly, and nonautomatable, FT levels are often calculated (cFT) rather than measured. However, the predictive accuracy of such estimates in routine use relative to laboratory measurements is not well defined.[10] ADAM questionnaire: The Saint Louis University ADAM questionnaire developed by Morley et al. has been widely used as a screening tool for detecting men at risk for androgen deficiency since its development in 2000. The ADAM questionnaire consists of ten questions that help determine if a male patient suffers from androgen deficiency (low testosterone) and whether or not further testing and follow-up are needed. It was shown to have a sensitivity of 88%, emphasizing its utility as a screening test. It was shown to be less specific, however, at 60%.[11] Low T: Low total T set from 250 to 300 ng/dl by other societies such as the American Urological Association has been established regardless of age following many large-scale population studies.[12]

The determinants of hypogonadism are: cFT, SHBG, HbA1C, erectile dysfunction, BMI etc.


  Results Top


[Table 1] shows the characteristics of the subjects. The mean age of the study subjects was 42.57 ± 7.4 years (mean ± standard deviation); 50% of the subjects were service holders, 15% retired, 12.5% were involved in business, 11.3% were skilled laborers, and the rest 11.2% were from groups comprising student, farming, etc. 38.8% of the subjects were smokers and 61.2% were nonsmokers. Family history of DM was present in 51.2% of the subjects. The mean of common clinical characteristics of the study subjects that include BMI, WC, HC, systolic BP, and diastolic BP of the subjects was 26 ± 5.1 kg/m2, 84.8 ± 8.4 cm, 83.8 ± 8.3 cm, 129.9 ± 11.4 mmHg, and 80.6 ± 7.7 mmHg, respectively.
Table 1: Descriptive analysis of sociodemographic characteristics of the participants (n=1940)

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[Table 2] shows the frequency of ADAM score of the participants. About two-thirds of them are ADAM positive.
Table 2: Androgen Deficiency in Aging Males questionnaire positive outcome (n=1940)

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[Table 3] shows the gonadal status in different glycemic control groups. It is shown that with decreasing the glycemic control, gonadal status went down.
Table 3: Distribution of gonadal status among glycosylated hemoglobin category according to Androgen Deficiency in Aging Males and total testosterone criteria (n=1940)

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[Table 3] depicts the gonadal status in different glycemic control groups. It is shown that with decreasing the glycemic control, gonadal status went down.

[Table 4] shows the distribution of gonadal status among HbA1c category according to cFT and ADAM criteria.
Table 4: Distribution of gonadal status among glycosylated hemoglobin category according to calculated free testosterone and Androgen Deficiency in Aging Males criteria (n=1940)

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[Table 5] shows that according to TT- and ADAM-positive criteria, 656 subjects (33.8%) were hypogonadal, whereas among the eugonadal subjects, 485 subjects (25%) had normal TT and ADAM negative and the remaining 217 subjects (11.2%) had only either low TT and were ADAM negative or had normal testosterone with ADAM positive. Five hundred and eighty-two subjects (30%) were only symptomatic or ADAM positive with normal TT and fell under the eugonadal group, as shown in [Table 6]. [Table 7] highlights the frequency of hypogonadism according to cFT and ADAM criteria where 364 subjects were hypogonadal (18.75%), whereas among the eugonadal subjects, 703 subjects (36.25%) had normal cFT and were ADAM negative and 873 subjects (45%) had normal cFT but were ADAM positive.
Table 5: Frequency of gonadal status among the study population according to total testosterone and Androgen Deficiency in Aging Males and according to calculated free testosterone and Androgen Deficiency in Aging Males criteria (n=1940)

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Table 6: Comparison of biochemical characteristics among the gonadal status according to total testosterone and Androgen Deficiency in Aging Male criteria

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Table 7: The correlations between calculated free testosterone and total testosterone with various clinical and biochemical parameters

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[Table 6] depicts the comparison of gonadal status with TT and ADAM criteria. TT and cFT were associated with hypogonadism. The comparison of hormonal and biochemical parameters among the hypogonadal and eugonadal groups according to TT and ADAM criteria is displayed in [Table 3]. There was a significantly difference among the groups for SHBG (21.7 ± 11.6 vs. 30.71 ± 22, P = 0.05) and blood sugar after 75 gram glucose (20.52 ± 7.72 vs. 17.37 ± 5.19, P = 0.03). It was found that HbA1c, fasting blood sugar, triglyceride, and total cholesterol were higher in the hypogonadal group (9.6 ± 2.4 vs. 8.8 ± 1.9, 20.52 ± 7.72 vs. 17.37 ± 5.19, 260.85 ± 148.58 vs. 221 ± 101.03, and 202 ± 43.1 ± 191.45 vs. 31.21, respectively) but without significant difference (P = NS for all). Similarly, no difference was found between the groups for high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels (P = NS for both). Accordingly, [Table 4] and [Table 5] show the comparison between the hypogonadal and eugonadal groups according to cFT and ADAM criteria that revealed a statistically significant difference between the two groups for several factors.

[Table 7] describes the correlation of clinical and biochemical parameters with total and calculated FT. The TT and cFT and cFT and SHBG have a significant association.

[Table 8] shows the predictive association of the clinical and biochemical variables with hypogonadism. ED and SHBG levels are positively associated with hypogonadism. According to the multiple regression, hypogonadism and SHBG were significant predictors for ED (P = 0.01 and 0.03, respectively).
Table 8: Logistic regression showing the predictive association of clinical and biochemical variables with hypogonadism

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  Discussion Top


The present study found that according to TT and ADAM criteria, about one-third of the newly detected T2DM male subjects were hypogonadal whereas about one-fifth were found to be hypogonadal according to cFT and ADAM criteria. In the present study, ADAM questionnaire was positive in 63.7% of the study subjects, with the highest number of patients complaining of fatigue (71.3%) and ED (56.3%) and mood changes (55%).

This is a bit higher than stated by Haynes et al.[13] in Indian population with diabetes.[14] They found around 30% of the T2DM to have hypogonadism according to ADAM scores. This might be due to the inclusion of patients in our study with longer duration of diabetes and of higher ages. ED was seen in significantly higher frequency in hypogonadal subjects (>80%) defined by cFT/TT and ADAM criteria. In other studies, ED was the most common presentation occurring in T2DM subjects with low testosterone.[12],[14],[15] Asaduzzaman et al. found 45.3% of the patients with T2DM to have ED according to International Index of Erectile Function (IIEF) scores.[16] In this, we found more T2DM patients to have ED according to cFT/TT and ADAM criteria. This can be easily explained by a higher sensitivity of these criteria.[17]

High frequency of fatigue and mood changes in the present study could be associated with classical symptoms and psychological impact of newly detected disease. Among hypogonadal subjects, according to cFT and ADAM criteria, the frequency of hypogonadotropic hypogonadism was 80% which, on the basis of TT and ADAM criteria, was 92.5%. Several studies described the association of androgen deficiency and various adverse consequences including sexual disorders, mood changes (irritability and depression), cognitive decline, reduced muscle, and bone mass leading to increased fracture risk, poor quality of life, and mortality.[18],[19],[20]

There was no significant difference for hypogonadism among either the HbA1c categories (P = 0.2) or age groups (P = 0.6). The hypogonadal and eugonadal groups significantly differed both according to TT and ADAM (81.5% vs. 43.4%, P = 0.01) and cFT and ADAM (93.3% vs. 47.7%, P ≤ 0.001) criteria for ED. There was a significant difference between the groups for SHBG (21.7 ± 11.6 vs. 30.71 ± 22, P = 0.05) by TT and ADAM criteria. Similarly, cFT and ADAM criteria also revealed statistically significant difference for SHBG (38.04 ± 19.90 vs. 25.28 ± 19.37 nmol/l, P = 0.03) and total cholesterol (211.40 ± 44.7 vs. 191.3 ± 32.64 mg/dl, P = 0.04). However, in both the groups, LH, FSH, triglyceride, HDL, and LDL did not differ significantly. cFT significantly correlated with age (r = ‒0.3503, P = 001) and SHBG (r = ‒0.37, P ≤ 0.01) whereas TT with SHBG (r = 0.58, P = 0.01). On the other hand, glycemic status was found to be related to hypogonadism and ED in patients with T2DM. In both the categories HbA1C, HbA1c has significant differences (P = 0.03 and 0.002, respectively). One Nigerian study reported findings and recommended achieving good glycemia for better gonadal and erectile functions.[21]

This study found SHBG to be significantly low in the hypogonadal group defined by the criterion of TT and ADAM but not with cFT. According to the multiple regression, hypogonadism and SHBG were significant predictors for ED (P = 0.01, 0.03, respectively). SHBG was also found to have a significant correlation with total and calculated FT but positively with the previous one and negatively with the latter. Multiple logistic regression analysis showed SHBG and TD are independent risk factors of ED.


  Conclusion Top


Symptomatic hypogonadism is frequent in males with newly detected T2DM and mostly is hypogonadotropic hypogonadal. Androgen deficiency symptoms are common in the study population, and ED is present in a significant proportion of hypogonadal subjects. ED and SHBG levels are positively associated with hypogonadism. Poor glycemic control has a significant effect on gonadal and erectile functions. Hence, routine screening of testosterone level and androgen deficiency symptoms is recommended in newly detected T2DM patients. A large-scale prospective study is required to assess the association, and interventional studies may be essential for the effective management of the condition.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Correspondence Address:
Shahjada Selim,
Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka
Bangladesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bjem.bjem_2_22




 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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