Effect of renal transplantation on sperm quality and sex hormone levels

Authors


Prof G. Pourmand, Renal Transplant Unit, Sina Hospital, Department of Urology, Tehran University of Medical Science, Tehran, Iran.
e-mail: gh_pourmand@hotmail.com

Abstract

OBJECTIVE

To assess the effect of successful renal transplantation on semen variables, sexual function and sex hormone profiles in a clinical trial.

PATIENTS AND METHODS

Thirty patients on haemodialysis underwent renal transplantation; before and after surgery, their sperm density, motility and morphology were analysed, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin and testosterone levels measured and compared, and sexual function assessed using an abbreviated version of the International Index of Erectile Function (IIEF), with a successful outcome defined as a level of satisfaction of 4 or 5 on a 5-point scale. The paired t-test was used to assess the statistically significance of differences in all analyses.

RESULTS

Sperm motility improved significantly (P < 0.001) but there were no significant changes in morphology or density (P = 0.33 and 0.068, respectively). Testosterone levels increased and FSH, LH and prolactin decreased significantly (P < 0.05) after renal transplantation. The IIEF showed that of the 30 patients, 14 were impotent before surgery and only six remained so afterward (P < 0.05).

CONCLUSION

Although sperm morphology and density did not improve after renal transplantation, there were highly significant changes in sperm motility. Hormonal levels in patients on haemodialysis improved after transplantation and returned to nearly normal; sexual function was also significantly better. Further studies are needed to confirm these results.

INTRODUCTION

The main objective in the therapy of end-stage renal disease is to prolong life and increase the quality of life in these patients. The restoration of sexual and reproductive functions are two vital considerations in this regard. Extra-hypothalamic, hypothalamic and hypophysiseal axis abnormalities are encountered in systemic diseases. About half of patients on haemodialysis have a decreased libido and impotence, associated with spermatogenic abnormalities and defects in testosterone biosynthesis. It is well established that sexual dysfunction persists in patients on maintenance haemodialysis, while it is claimed that renal transplantation restores libido and potency in uraemic men [1,2]. The mechanisms of hormonal disturbances and their role in the pathogenesis of the impotence in uraemia are not clearly understood.

Attempts to correlate the serum levels of these hormones with impotence have not been successful; this is not surprising as the pathogenesis of impotence is multifactorial. High FSH, LH and low testosterone levels are reported in uraemic men and the testosterone level is within the normal range in men with successfully transplanted kidneys. In the present study we evaluated the effect of successful renal transplantation on semen variables, sexual function and sex hormone profiles in a clinical trial.

PATIENTS AND METHODS

The study comprised 30 men undergoing haemodialysis (24–52 years old) who received a transplanted kidney at our centre between 1999 and 2001. They had been on haemodialysis two to three times weekly (4 h each session) for several months (≥ 6 months).There were no severe complications. Exclusion criteria were: (i) erythropoietin usage (> 3 months), as erythropoietin therapy has been shown to improve sexual function in men on dialysis, with several studies suggesting a direct effect on endocrine function as well as correcting the anaemia [3]; (ii) diabetic patients; (iii) graft rejection within the first 6 months after transplantation; (iv) division of the spermatic cord vessels, as this might affect testicular function; (v) unable to be followed up.

Patients were assessed at 6 months after successful live unrelated renal transplantation; all had a well functioning graft and a serum creatinine level of 9–22 mg/L. Immunosuppression was administered (azathioprine 2 mg/kg, prednisolone, 5–15 mg and cyclosporin A 8 mg/kg) daily as maintenance.

The patients were examined physically and all were assessed by measuring the plasma level of testosterone, LH, FSH, prolactin and by semen analysis before and 6 months after transplantation. Plasma testosterone, FSH, LH and prolactin levels were measured using radioimmunoassay techniques, the normal ranges being 2–10 mIU/mL for FSH and LH, 2.4–10 ng/mL for testosterone and 2–10 ng/mL for prolactin. The same kits and laboratory techniques were used before and after transplantation.

Semen was analysed after 3 days of sexual abstinence and within 30–45 min of ejaculation, assessing the semen volume, sperm density, sperm motility and morphology. Normal semen quality was defined as a total sperm count of > 40 × 106, with more than half the sperm showing forward progression and > 15% having normal morphology, by strict criteria, and a volume of ≥ 2 mL (WHO criteria). In none of the patients was the testis biopsied.

Sexual function was measured before and after transplantation using an abbreviated version of the International Index of Erectile Function (IIEF), with a successful outcome defined as a level of satisfaction of 4 or 5 points on the 5-point scale. The paired t-test was used to assess the statistical significance of any differences in all the analyses.

RESULTS

During dialysis, 11 of 30 patients had suboptimal levels of testosterone and the levels of LH, FSH and prolactin were greater than normal in 13, 14 and 11 patients, respectively (Table 1). After transplantation, the testosterone level became normal in five patients, LH in six, FSH in four and prolactin in eight of those with initially abnormal values. These changes of testosterone, LH, FSH, and prolactin were all statistically significant (P < 0.05; Table 1). None of the patients had a significant arteriovenous shunt, as this may change the metabolic clearance rate of testosterone [1].

Table 1. Hormonal levels and sperm quality during maintenance dialysis and after transplantation
Mean (sd)
variable
DialysisTransplantP
Hormone levels
Testosterone, ng/mL  3.92 (2.5)  4.5 (1.92)0.005
LH, mIU/mL  8.6 (4.6)  7.04 (3.32)< 0.001
FSH, mIU/mL  9.6 (5.1)  8.75 (4.76)0.01
Prolactin, ng/mL16.6 (10.5)10.52 (5.55)< 0.001
Semen quality
Sperm motility50.62 (9.97)56.56 (7.46)< 0.05
Sperm density60.62 (10.46)64.06 (9.34)> 0.05
Volume  3.21 (0.63)  3.09 (0.41)> 0.05
Sperm morphology55.31 (11.61)56.87 (7.71)> 0.05

During dialysis only 13 of 30 patients had normal sperm values; after transplantation, 22 had normal sperm values. The improvement in sperm motility was statistically significant, but changes in sperm density, morphology and volume were not (Table 1). Of the 30 patients, 14 were impotent before surgery but only six patients remained so 6 months after transplantation (P < 0.05).

DISCUSSION

Derangements in the serum levels of testosterone, FSH, LH, and prolactin have been reported in uraemic patients and those treated with haemodialysis [1]. Testosterone levels are usually subnormal during dialysis. Leydig cell dysfunction [4,5], a central defect at the level of hypothalamus involving the regulation of LHRH, or a combination of these effects may be responsible for low testosterone levels [6,7]. Low testosterone levels are commonly associated with elevated LH levels.

Testosterone production is reduced but its metabolic clearance rate is normal except in haemodialysis patients with a significant arteriovenous shunt; these patients may have an accelerated metabolic clearance rate [1].

In the present study, during haemodialysis the testosterone level remained low while LH levels were elevated in most men. After transplantation, this hormonal profile was reversed, with increases in testosterone and decreases in LH level to near normal values (P = 0.005 and 0.001, respectively), probably indicating a difference in the ability of haemodialysis and transplantation to reverse the dysfunction in the pituitary Leydig cell axis in advanced uraemia.

Procci et al.[1] reported that serum levels of FSH are usually normal, but some patients may have high values under haemodialysis. The prolactin level is increased in uraemic patients, possibly by increased secretion or its prolonged half-life [8]. In the present study FSH and prolactin levels were higher than normal during haemodialysis; 6 months after transplantation, FSH and prolactin levels decreased significantly (both P = 0.001).

The quality of semen is poor in uraemic men [9,10]; the seminal variables remain suboptimal during dialysis and successful renal transplantation is credited with producing an overall improvement in quality [10,11]. In the present study the seminal volume, morphology and density showed no significant improvement, but sperm motility did. This change, while statistically significant, was not very dramatic.

Holdsworth et al.[9] maintained that the major factor contributing to the poor quality of semen in advanced uraemia is damage to spermatogenesis, possibly as a result of hormonal deficiency and severe germ cell damage that might be irreversible. Abnormal testicular function in haemodialysis patients could be caused by high oestrogen levels, as is a decreased or absent libido [12]. There can be abnormal testis histology in haemodialysis patients. Hypospermatogenesis, seminiferous tubule destruction, maturation arrest and germinal aplasia are common in these patients [6,7,13,14]. According to Prem et al.[13] advanced germ cell failure during haemodialysis is usually irreversible even after transplantation, but moderate germ cell failure is usually recoverable.

About half of men undergoing dialysis are impotent [15]; many factors are involved, including decreased testosterone level, autonomic neuropathy, accelerated vascular disease, medication, worsening of the primary disease, and psychological stress. It is commonly accepted that low serum testosterone levels might correlate with low sexual desire and erectile difficulties. Transplanted patients had a significant improvement in sexual activity and a return of testosterone to normal values [4]. Low testosterone levels might also decrease the frequency, volume and quality of ejaculation.

Salvatierra et al.[16] studied a group of patients who underwent successful renal transplantation, and potency was restored in 75%; however, impotence was reported to increase six-fold after renal transplantation [17]. Diabetes mellitus, hypertension, uraemia, atherosclerosis and occlusion of hypogastric arteries were all suspected to be a risk factor, but only age ≥ 40 years was deleterious to potency [17]. Pach et al.[18] reviewed some psychological aspects of sexual function in these patients, and concluded that psychological factors might play a role. The sexual function of impotent men in the present study improved significantly (eight of 14 impotent patients recovered) after successful renal transplantation.

We conclude that the dysfunction of steroidogenesis and spermatogenesis induced by uraemia is not corrected by haemodialysis. In contrast, after successful renal transplantation, the testosterone, LH, FSH and prolactin levels became normal; spermatogenesis and sexual function is improved significantly.

ACKNOWLEDGEMENTS

We thank Dr Alvaro Morales for editorial assistance with the manuscript. We also wish to thank Dr M. Malek for his help.

Abbreviations
IIEF

International Index of Erectile Function.

Ancillary