Hypergonadotropic hypogonadism in Nigerian men with type 2 diabetes mellitus
, 3, 4, 4
Abstract
Background. Studies have reported a higher preva-lence of hypogonadism in men with type 2 diabetes mellitus (T2DM) than non-diabetic men. The pattern of hypogonadism in men with T2DM using gonado-tropin-releasing hormone (GnRH) stimulation test in Sub-Saharan Africa is unknown.
Objective. This study was conducted to determine the prevalence and pattern of hypogonadism in Nigerian men with T2DM.
Methods. A cross-sectional study involving 358 men with T2DM and 179 non-diabetic men as controls. Androgen Deficiency in the Ageing Male (ADAM) questionnaire was administered. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) both at 0 hours and 4 hours after subcutaneous buserelin injec-tion, fasting total testosterone (TT), fasting plasma glucose and glycated haemoglobin were measured. Ninety-nine men with T2DM selected by randomiza-tion using a computer underwent GnRH stimulation test, with subcutaneous injection of 100 micrograms of buserelin.
Results. The mean TT of T2DM men was significantly lower compared to the controls (8.79 ± 3.35 nmol/L vs 15.41 ± 3.79 nmol/L, p < 0.001). The prevalence of hypogonadism in T2DM men was 80.4%, comprising 38.5% of severe hypogonadism and 41.9% mild hypogonadism. The mean LH and FSH levels were significantly higher in T2DM men than the controls (9.62 ± 6.82 IU/L vs 8.24 ± 5.91 IU/L, p = 0.022 and 8.50 ± 8.17 IU/L vs 5.17 ± 3.89 IU/L, p < 0.001 respectively). There was a statistically significant exaggerated response in mean (±SD) LH and FSH levels at 4 hours after buserelin in-jection compared to the 0-hour levels (58.58 ± 40.72 IU/L vs 8.38 ± 6.10 IU/L, p < 0.001 and 23.03 ± 18.02 IU/L vs 8.41 ± 7.45 IU/L, p < 0.001 respectively) in men with T2DM who had GnRH stimulation tests.
Conclusion. This study shows that the prevalence of hypogonadism in men with T2DM is significantly higher than in non-diabetic men with mild hypogonadism accounting for most cases. Hypergonadotropic hypo-gonadism occurs more frequently in men with T2DM in Nigeria.
Keywords: hypergonadotropic hypogonadismhypogonadismtype 2 diabetes mellitusGnRH stimulationtotal testosterone
References
- Guariguata L, Linnenkamp U, Beagley J, et al. The IDF Diabetes Atlas methodology for estimating global prevalence of hyperglycaemia in pregnancy. Diabetes Res Clin Pract. 2014; 103(2): 186–196.
- Mbanya J, Motala A, Sobngwi E, et al. Diabetes in sub-Saharan Africa. The Lancet. 2010; 375(9733): 2254–2266.
- Sobngwi E, Mauvais-Jarvis F, Vexiau P, et al. Diabetes in Africans. Part 1: epidemiology and clinical specificities. Diabetes Metab. 2001; 27(6): 628–634.
- Akinkugbe OIA, Johnson T. Non-communicable diseases in Nigeria. The final report of national survey. Lagos, Federal Ministry of Health — National Expert Committee on Non-Communicable Diseases. 1997: 12–41.
- Nyenwe EA, Odia OJ, Ihekwaba AE, et al. Type 2 diabetes in adult Nigerians: a study of its prevalence and risk factors in Port Harcourt, Nigeria. Diabetes Res Clin Pract. 2003; 62(3): 177–185.
- Oputa R. National diabetes screening programmes. Diabetes International. 2009; 17: 9–11.
- Dhatariya K, Nagi D, Jones TH. ABCD position statement on the management of hypogonadal males with type 2 diabetes. Practical Diabetes International. 2010; 27(9): 408–412.
- Nieschlag E, Behre HM, Bouchard P, et al. Testosterone replacement therapy: current trends and future directions. Hum Reprod Update. 2004; 10(5): 409–419.
- Fakih M. Prevention, diagnosis, and management of osteoporosis-related fracture. J Am Osteopath Assoc. 2009; 109(3): 191–193.
- Kapoor D, Malkin CJ, Channer KS, et al. Androgens, insulin resistance and vascular disease in men. Clin Endocrinol (Oxf). 2005; 63(3): 239–250.
- Traish AM, Saad F, Guay A. The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl. 2009; 30(1): 23–32.
- Vikan T, Schirmer H, Njølstad I, et al. Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men. Eur J Endocrinol. 2010; 162(4): 747–754.
- Corona G, Mannucci E, Petrone L, et al. Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic. Int J Impot Res. 2006; 18(2): 190–197.
- Grossmann M, Thomas MC, Panagiotopoulos S, et al. Low testosterone levels are common and associated with insulin resistance in men with diabetes. J Clin Endocrinol Metab. 2008; 93(5): 1834–1840.
- Ogbera OA, Sonny C, Olufemi F, et al. Hypogonadism and subnormal total testosterone levels in men with type 2 diabetes mellitus. J Coll Physicians Surg Pak. 2011; 21(9): 517–521.
- Onung SI, Young EE, Ugwu TE, et al. Hypogonadism in Nigerian men with type 2 diabetes mellitus. International Journal of Diabetes in Developing Countries. 2016; 37(3): 254–261.
- Ugwu TE, Ikem RT, Kolawole BA, et al. Clinicopathologic assessment of hypogonadism in men with type 2 diabetes mellitus. Indian J Endocrinol Metab. 2016; 20(5): 667–673.
- Kemp T, Rheeder P. The prevalence and association of low testosterone levels in a South African male, diabetic, urban population. Journal of Endocrinology, Metabolism and Diabetes of South Africa. 2015; 20(2): 92–97.
- Hackett G, Cole N, Deshpande A, et al. Biochemical hypogonadism in men with type 2 diabetes in primary care practice. The British Journal of Diabetes & Vascular Disease. 2009; 9(5): 226–231.
- Ganesh HK, Vijaya Sarathi HA, George J, et al. Prevalence of hypogonadism in patients with type 2 diabetes mellitus in an Asian Indian study group. Endocr Pract. 2009; 15(6): 513–520.
- Kapoor D, Aldred H, Clark S, et al. Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: correlations with bioavailable testosterone and visceral adiposity. Diabetes Care. 2007; 30(4): 911–917.
- Asare-Anane H, Ofori E, Yeboah F, et al. Primary hypogonadism in Ghanaian men with type 2 diabetes mellitus. IJSTR. 2013; 2(5): 310–5.
- American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hypogonadism in Adult Male Patients—2002 Update. Endocrine Practice. 2002; 8(6): 439–456.
- Wilson DA, Hofman PL, Miles HL, et al. Evaluation of the buserelin stimulation test in diagnosing gonadotropin deficiency in males with delayed puberty. J Pediatr. 2006; 148(1): 89–94.
- Paruk IM, Pirie FJ, Nkwanyana NM, et al. Prevalence of low serum testosterone levels among men with type 2 diabetes mellitus attending two outpatient diabetes clinics in KwaZulu-Natal Province, South Africa. S Afr Med J. 2019; 109(12): 963–970.
- Morley JE, Charlton E, Patrick P, et al. Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism. 2000; 49(9): 1239–1242.
- Nieschlag E, Swerdloff R, Behre HM, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. Int J Androl. 2005; 28(3): 125–127.
- Tan RS, Pu SJ. Impact of obesity on hypogonadism in the andropause. Int J Androl. 2002; 25(4): 195–201.
- Dapel Z. Poverty in Nigeria: Understanding and bridging the divide between north and south. Centre for Global Development. 2018.
- Dhindsa S, Prabhakar S, Sethi M, et al. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab. 2004; 89(11): 5462–5468.
- Rabijewski M, Papierska L, Zgliczyński W, et al. The incidence of hypogonadotropic hypogonadism in type 2 diabetic men in Polish population. Biomed Res Int. 2013; 2013: 767496.
- Kim JS, Kim BS, Jeon JaY, et al. Testosterone deficiency associated with poor glycemic control in korean male diabetics. Endocrinol Metab (Seoul). 2014; 29(3): 300–306.
- Haffner SM, Mykkänen L, Valdez RA, et al. Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. J Clin Endocrinol Metab. 1993; 77(6): 1610–1615.
- Madhu SV, Aslam M, Aiman AJ, et al. Prevalence of hypogonadism in male Type 2 diabetes mellitus patients with and without coronary artery disease. Indian J Endocrinol Metab. 2017; 21(1): 31–37.
- Phillips GB. Relationship between serum sex hormones and the glucose-insulin-lipid defect in men with obesity. Metabolism. 1993; 42(1): 116–120.
- Seidell JC, Björntorp P, Sjöström L, et al. Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels, but negatively with testosterone levels. Metabolism. 1990; 39(9): 897–901.
- Asare-Anane H, Ofori E, Agyemang Y, et al. Obesity and testosterone levels in Ghanaian men with type 2 diabetes. Clin Diabetes. 2014; 32(2): 61–65.
- Al Hayek AA, Khawaja NM, Khader YS, et al. The prevalence of Hypogonadism among diabetic and non-diabetic men in Jordan. J Diabetes Complications. 2014; 28(2): 135–140.
- Teka S, Kinde S, Dedefo G, et al. Hypogonadism and associated risk factors in male patients with type 2 diabetes mellitus attending the diabetic clinic of Tikur Anbessa Specialized Teaching Hospital, Addis Ababa, Ethiopia. Journal of Endocrinology, Metabolism and Diabetes of South Africa. 2018; 24(1): 16–22.
- Kumar P, Kumar N, Thakur DS, et al. Male hypogonadism: Symptoms and treatment. J Adv Pharm Technol Res. 2010; 1(3): 297–301.
- Bodie J, Lewis J, Schow D, et al. Laboratory evaluations of erectile dysfunction: an evidence based approach. J Urol. 2003; 169(6): 2262–2264.
- Traish AM, Goldstein I, Kim NN. Testosterone and erectile function: from basic research to a new clinical paradigm for managing men with androgen insufficiency and erectile dysfunction. Eur Urol. 2007; 52(1): 54–70.
- Galloway M. Testosterone deficiency syndrome: a common factor in type 2 diabetes and erectile dysfunction patients. Prac Diab Int. 2008; 25: 3–10.
- Tripathy D, Dhindsa S, Garg R, et al. Hypogonadotropic hypogonadism in erectile dysfunction associated with type 2 diabetes mellitus: a common defect? Metab Syndr Relat Disord. 2003; 1(1): 75–80.
- Alhayek A, Khader Y, Jafal S, et al. Hypogonadism among Jordanian men with type 2 diabetes: Prevalence and associated factor. International Journal of Diabetes Mellitus. 2015; 3(1): 31–36.
- Rabijewski M, Papierska L, Zgliczyński W, et al. The incidence of hypogonadotropic hypogonadism in type 2 diabetic men in Polish population. Biomed Res Int. 2013; 2013: 767496.