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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2004  |  Volume : 15  |  Issue : 4  |  Page : 447-454
Effect of Age on Pituitary Gonadal Hormonal Responses of Saudi Male Patients on Hemodialysis


1 Department of Pathology, Riyadh Armed Forces Hospital, Riyadh, Saudi Arabia
2 Department of Biochemistry, College of Science, King Saud University Riyadh, Saudi Arabia
3 Department of Nephrology, Riyadh Armed Forces Hospital, Riyadh, Saudi Arabia

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   Abstract 

The pituitary gonadal axis of men with chronic renal failure is disturbed even when there is moderate reduction of the glomerular filtration rate. This axis is also disturbed in the ageing male. The present investigation was undertaken to study the pituitary gonadal hormonal response in Saudi male patients, belonging to two different age-groups, on regular hemodialysis (HD). Male patients on HD were divided into two groups. Group one included 24 individuals under 45 years of age and group two had 50 subjects > 45 years. Age­matched healthy individuals were used as controls. Serum levels of total and free testosterone were significantly reduced in patients >45 years of age when compared to patients <45 years of age. Also, the levels of follicle stimulating hormone (FSH) and leutenizing hormone (LH) were significantly increased in both the groups when compared with their age-matched controls. However, the serum levels of FSH, LH and sex hormone binding globulin (SHBG) were not significantly different between patients >45 years and those <45 years of age. Similarly, there was no significant difference in the hemoglobin levels between the two groups. The results of this study, suggest that disturbances in the pituitary gonadal hormonal responses in men on HD and >45 years of age may be more severe than men <45 years of age. Further studies are warranted to understand this observation.

Keywords: Pituitary gonadal hormones, Hemodialysis, Testosterone, Age.

How to cite this article:
Sobki SH, Al-Etah H, El Gezeery A, Al Khader A. Effect of Age on Pituitary Gonadal Hormonal Responses of Saudi Male Patients on Hemodialysis. Saudi J Kidney Dis Transpl 2004;15:447-54

How to cite this URL:
Sobki SH, Al-Etah H, El Gezeery A, Al Khader A. Effect of Age on Pituitary Gonadal Hormonal Responses of Saudi Male Patients on Hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2004 [cited 2019 Oct 19];15:447-54. Available from: http://www.sjkdt.org/text.asp?2004/15/4/447/32876

   Introduction Top


End-stage renal disease (ESRD) is a growing problem world wide. In the United States alone, there were 232,000 patients on dialysis in 1997 and the number is anticipated to reach 600,000 in 2010. [1] The incidence of ESRD has also risen in the Saudi population. The number of patients requiring dialysis in the Kingdom of Saudi Arabia has increased from 370 in 1982 [2] to 5706 in 1999 and is estimated to reach 9242 in 2011. [3] Furthermore, the mean age of the dialysis population has also increased over time. In the early 80's the mean age of patients on hemodialysis (HD) in Saudi Arabia ranged between 37.9 to 40.9 years. [4],[5] According to a recent report from the same group, [6] the mean age has risen to 51.3 ± 1.1 years. Moreover, patients over 50 years of age constituted 59% of the total on HD compared to only 10% in the early 80's. [3] This change in age distribution of patients on dialysis is seen in America and Europe as well, the mean age being 52.3 years and 58.2 years respectively. [7] Also, in 1992, only 9% of the dialysis patients in Europe were over 65 years of age as against 38% in 1997, [8] while in the Asia Pacific region, six of the 12 countries had more than 35% of the dialysis patients aged above 60 years. [9]

Renal failure adversely affects reproductive tissue as a result of direct uremic toxicity. [10],[11] Impaired sexual function among patients with ESRD is well documented. [12],[13],[14],[15],[16],[17] Although the genesis of sexual dysfunction is multifactorial and is primarily organic in origin, disturbances in the pituitary gonadal axis of men with renal disease has been seen with only moderate reductions in the glomerular filtration rate, and this progressively worsens as the renal failure progresses. [18] Chronic renal failure is also associated with testicular damage resulting in altered spermatogenesis and endocrine function. [18],[19] The pituitary gonadal axis is also altered in the ageing male. [20]

The present investigation was undertaken to study the pituitary testicular hormonal responses of Saudi male patients on main­tenance HD belonging to two different age­groups.


   Material and Methods Top


Seventy-four male patients on maintenance HD were studied after obtaining informed consent. The patients were divided into two groups. The first group (Group 1) included 24 individuals in the age-group of 20-45 years and the second group (Group 2) had 50 subjects above 45 years of age. The mean age ±.SD of the two groups was 34.21 ± 7.1 and 57.6 ± 8.4 years respectively. The duration on dialysis for the two groups was 4.2 ± 3.3 years and 3.9 ± 4.1 years respectively. All the patients were administered erythropoietin from the beginning of HD. The etiology of ESRD in the two groups is shown in [Figure - 1] and [Figure - 2]. Age-matched healthy blood donors (21 aged < 45 years and five above > 45years), who were not on any specific medications, were used as controls.

Venous blood samples were collected from the patients before dialysis into different tubes for hematological, biochemical and hormonal analysis. Red blood cells and hemoglobin concentration were measured by using coulter STK counter machine (Coulter Electronics USA). Random blood glucose, sodium, pota­ssium, chloride, urea, creatinine, uric acid, total protein, calcium, phosphorous, cholesterol and triglycerides were measured by using the Hitachi 917 clinical chemistry analyzer (Roche Diagnostics). Analysis of hormones in the serum was performed by using commercially available kits. Leutenizing hormone (LH) and follicle stimulating hormone (FSH) were analyzed by using enzymum test kits and Boehrin9er Mannheim ES 700 hormone analyzer [1] (Boehringer Mannheim, Germany). Total testosterone and sex hormone binding globulin (SHBG) were measured by using immulite kits (Diagnostic products Corporation, CA, CA, USA), while free testosterone levels were analyzed by using DPC coat a count free testosterone radio immunoassay kit. [22]

Statistics

Data were analyzed for departure from nor­mality and for equality of variances. One way ANOVA with Bonferonni's post hoc multiple comparison test or Kruskalwallis test with Mann Whitney U test were used. A p value of <0.05 was considered as significant. Statistical analysis was performed by using the SPSS (version 10.0) statistics program, Chicago.


   Results Top


The etiology of ESRD in the two study groups is shown in [Figure - 1] and [Figure - 2]. There was no significant difference in the duration of the disease and dialysis, frequency of dialysis and residual renal function between the two groups of patients [Table - 1]. The difference in the serum levels of FSH, LH and SHBG was also statistically insignificant between the two groups of patients [Figure - 3],[Figure - 4] However, a significant increase in the levels of FSH and LH was observed in both groups of patients when compared with their age-matched controls [Figure - 3]. The serum levels of total testosterone and free testosterone were signi­ficantly reduced in Group 2 patients when compared with Group 1 [Figure - 4]. Also, the free testosterone levels were significantly lower in both groups of patients as compared with their age-matched controls [Figure - 4]. Although the hemoglobin levels were not significantly different between the two groups of patients, the levels were significantly low when compared with their age-matched controls [Table - 1]. The levels of uric acid, creatinine, phosphate and cholesterol were significantly increased in Group 1 patients when compared to Group 2 [Table - 1]. There was no statistically significant difference in the levels of protein, sodium, potassium calcium, urea, and trigly­cerides between the two patient groups [Table1].


   Discussion Top


The results of this study suggest that distur­bance in the pituitary gonadal response in males on HD is more severe in those aged >45 years than those <45 years of age. Decreased levels of total and free testosterone in men aged >45 years is supported by the earlier study of Sasagawa et al, [23] who observed a negative correlation between serum levels of total and free testosterone and age in patients on HD. Recent studies also strongly support the concept that both total and bioavailable circulating testosterone levels are lowered at a constant rate with ageing, independent of obesity, illness, medication and alcohol intake. [24],[25] Advanced age and chronic illness was also suggested to limit the hormonal res­ponse in elderly patients undergoing HD and on erythropoietin. [26] It thus appears that testi­cular dysfunction becomes more severe with increasing age in patients on HD. Furthermore, the lower levels of testosterone and free testosterone are associated with increased levels of SHBG. [27] In our study, although the levels of testosterone were decreased, no significant difference was observed in the levels of serum SHBG between the two groups [Figure - 4]. The mechanism behind this lack of correlation between SHBG and testosterone levels is not clear, although this main testosterone carrier protein has been shown to be in the normal range in uremic men. [28]

There was no significant difference in the serum levels of FSH, LH and SHBG between the two patient groups [Figure - 3],[Figure - 4]. How­ever, when compared with their age-matched controls, both groups of patients had a signi­ficantly higher serum FSH and LH levels [Figure - 3]. The lack of any significant difference in the levels of FSH and LH between the two groups in spite of a larger percentage of diabetic patients in the second group is supported by the earlier observation that hormonal responses of patients on dialysis are independent of the presence of diabetes mellitus. [9]

The function of the pituitary gonadal axis in HD patients is disturbed. [30],[31] The plasma concentrations of FSH and LH are elevated in uremic men. [18],[32] Elevated LH levels have been found in early renal insufficiency and this progressively rises with deteriorating renal function. [33] Enhanced LH secretion is a manifestation of the diminished release of testosterone from Leydig cells, since testosterone levels regulate LH release through an inhibitory feedback. [19] Our results of a significant increase in the levels of FSH and LH are in agreement with these reports. Moreover, levels of inhibin B, a hormone of gonadal origin, reflect the functional state of the seminiferous epithelium and are involved in the feedback of the pituitary gonadal hormone levels. [34] Inhibin B production is directly proportional to the amount of spermatogenesis. [35] Its levels are lower in men with spermatogenic damage, with undetectable levels in azoospermic men. [36],[37] Chronic renal failure is also associated with impaired spermatogenesis and testicular damage. [15] In addition to impaired spermato­genesis, the testes also show evidence of impaired endocrine function and drop in the levels of total and free testosterone. An increase in the levels of FSH and LH, albeit statisti­cally insignificant, [Figure - 3] and a decrease in the levels of testosterone in patients >45 years of age, suggest a more severe damage to the spermatogenic process in this group.

Administration of EPO has been shown to improve sexual function in patients with chronic renal failure with a normalization of the hypothalamo-pituitary-testicular axis. [38],[39] The increased basal plasma FSH and LH levels were attenuated while the decreased testosterone levels were slightly elevated following EPO treatment. [40],[41] However, other investigators have reported that EPO treat­ment did not result in any significant decrease in the previously elevated levels of FSH, LH and prolactin in patients on HD although it did increase the levels of testosterone. [33] Steffensen and Aunsholt [42] (1993) also failed to observe any changes in the serum levels of sex hormones (FSH, LH, testosterone and prolactin) in HD patients on EPO. These diffe­rent reports on the levels of sex hormones in HD patients and the results of the present study support the observation that the effect of EPO on the disturbed sexual function is probably as complex as the pathogenesis. [42]

A significant increase in the levels of blood glucose in Group 2 patients is due to the higher percentage of diabetic patients in this group. Although the hemoglobin (Hb) concen­trations were lower in both groups of patients when compared with their age-matched controls, no significant change was observed between the two patient groups [Table - 1], suggesting an ameliorating effect of EPO on ESRD­induced anemia irrespective of age. Earlier studies have also shown an attenuation of uremia-induced decrease in Hb levels of HD patients upon administration of EPO. [17],[39]

In conclusion, the results of this study suggest that disturbances in the pituitary gonadal hor­monal responses of men >45 years of age undergoing HD may be more severe than men <45 years of age resulting in a decrease in the levels of free and total testosterone. Treatment with EPO does not restore the gonadal function. Further studies are warranted to understand the disturbed pituitary gonadal hormonal axis in elderly men on HD and understand better its pathogenesis and possible therapeutic modalities.


   Acknowledgements Top


The authors wish to thank Mr. M. Al-Jundabi and all the staff in the Dialysis Unit (RKH), Mr. M. Fayoumi, and the Pathology staff who contributed to this study in their respective capacities.

 
   References Top

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42.Steffensen G, Aunsholt NA. Does erythro­poietin cause hormonal changes in haemo­dialysis patients? Nephrol Dial Transplant 1993;8:1215-8.  Back to cited text no. 42  [PUBMED]  [FULLTEXT]

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Correspondence Address:
Samia H Sobki
Department of Pathology, Riyadh Armed Forces Hospital, P.O. Box 7897, Riyadh 11159
Saudi Arabia
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