Archives of Andrology

Journal of Reproductive Systems

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Glutathione Therapy for Male Infertility

A. Lenzi, F. Lombardo, L. Gandini, F. Culasso & F. Dondero

To cite this article: A. Lenzi, F. Lombardo, L. Gandini, F. Culasso & F. Dondero (1992) Glutathione
Therapy for Male Infertility, Archives of Andrology, 29:1, 65-68, DOI: 10.3109/01485019208987710

To link to this article: https://doi.org/10.3109/01485019208987710

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 GLUTATHIONE THERAPY FOR MALE
INFERTILITY

A. LENZI, F. LOMBARDO, L. GANDINI, F. CULASSO,

and F. DONDERO

Eleven infertile men were treated with glutathione (600 mgiday IM) for 2 months. The patients were
suffering from dyspermia associated with various andrological pathologies. Standard semen and com-
puter analyses of sperm motility were carried out before treatment and after 30 and 60 days of therapy.
Glutathione exerted significant effect on sperm motility patterns. Glutathione appears to have a thera-
peutic effect on some andrological pathologies causing male infertility.

Key Words: Glutathione; Dysperrnia; Male infertility.

INTRODUCTION

The sulfydryl groups play an important role in sperm motility and sperm metabolism. The
natural sulfydryl-containing constituents of semen, such as cystein, glutathione (y-glutamyl-
cystenyl-glycine), and ergothioneine, efficiently counteract the sperm-immobilizing effects of
many toxic substances [ 11. The purpose of this study was to evaluate the pharmacologic use of
glutathione therapy in andrological pathologies associated with dyspermia.

MATERIALS AND METHODS

Glutathione therapy (600 mgiday IM) was applied for 2 months in a pilot group of 1 1 infertile men
with dyspermia associated with previous bilateral orchiepididimitis (2 cases), prostato-vescicular germ-
free chronic inflammation (6 cases), varicocele (2 cases), and antisperm antibodies (1 case). We carried
out standard semen analysis (WHO Standard Procedure) and a computer analysis of sperm motility (Cell
Soft, Cry0 Resources) before treatment and after 30 and 60 days of therapy. The following variables
were evaluated: sperm concentration (n x 106/mL), total sperm motility (% at the 2nd hour after
ejaculation), forward motility (% at the 2nd hour after ejaculation), morphology ( % of atypical forms),
velocity (Fmis), linearity index, amplitude of lateral head displacement (ALH, Fm), and frequency of
beat cross (BCF, Hz). Statistical analysis was carried out by Student’s t test between paired means of all
variables, at different times (0, 30, and 60 days); a Wilcoxon test confirmed the results obtained by the t
test.

From the University Laboratory of Seminology & Immunology of Reproduction, 5th Medical Clinic, and the
Department of Experimental Medicine, University of Rome “La Sapienza,” Rome, Italy.
Address correspondence to Dr. Andrea Lenzi, V Medical Clinic, University of Rome “La Sapienza,” Policlinico
“Umberto I,” 00161 Rome, Italy.

ARCHIVES OF ANDROLOGY 29:65-68 (1992)

Copyright 0 1992 by Hemisphere Publishing Corporation 65
66 A. Lenzi et al.

RESULTS

Glutathione therapy has a statistically significant effect on sperm motility patterns (Tables
1, 2). In particular, a significant difference between baseline and 60-day checks was observed
in the percentage of forward motility and in the parameters of the computer analysis of sperm
motility (velocity, linearity, ALH, and BCF). A significant reduction in the percentage of
atypical forms was also observed after 30 days. Sperm motility improved in patients with
previous orchiepididymitis and patients with varicocele. Good results were observed in four
out of six patients with prostato-vescicular inflammation. No modifications were observed
either in semen parameters or in antibody titer in the case with antisperm immune pathology.

TABLE 1 Means, Standard Deviations, and Medians at Different Times of Glutathione

Therapy

Variable Baseline After 30 days After 60 days

Concentration (106/mL)
Mean 23.45 26.27 25.55
SD 8.42 9.53 9.25
Median 22.00 25.00 25.00
Total motility (% after 2 h)
Mean 29.09 32.73 37.21
SD 12.41 10.34 11.26
Median 30.00 35 .00 40.00
Forward motility (% after 2 h)
Mean 17.73 21.36 26.36
SD 9.32 8.69 10.27
Median 15.00 20.00 30.00
Morphology ( % atypical forms)
Mean 42.27 40.09 39.55
SD 6.90 6.55 7.23
Median 40.00 38.00 35.00
Velocity (nim/s)
Mean 35.46 38.44 43.24
SD 3.81 4.72 6.01
Median 35.40 39.70 45.10
Linearity index
Mean 3.24 3.73 4.33
SD 0.70 0.70 0.79
Median 3.20 4.00 4.50
ALH (Irm)
Mean 2.73 3.18 3.52
SD 0.31 0.39 0.40
Median 2.70 3.20 3.50
BCF (Hz)
Mean I 1.86 12.31 12.60
SD 0.17 0.77 0.82
Median 12.10 12.50 12.70
 Glutathione and Male Infertility 67

TABLE 2 t Tests Between Paired Means (at Different Times) of Semen Characteristics

Variable 30 vs 0 days 60 vs 0 days 60 vs 30 days

Concentration (* 1o6/mL)
f 1.77 1.87 -0.54
sig ,107 .090 ,602
Total motility (% after 2 h)
t 2.19 2.84 2.19
sig .054 ,018 ,053
Forward motility (% after 2 h)
1 2.67 4.50 3.32
sig .024 ,001 ,008
Morphology (% atypical forms)
t - 1.72 -3.28 - 0.47
sig ,117 .008 .651
Velocity (mm/s)
1 3.98 5.49 4.88
sig ,003 ,000 ,001
Linearity
t 4.80 6.04 4.13
sig ,001 ,000 .002
ALH (dW
t 7. I3 8.90 5.68
sig ,000 ,000 .Ooo
BCF (Hz)
r 2.17 2.74 2.26
sig ,055 .02 1 ,048

Note. t , f test; sig, significance probability

DISCUSSION

The glutathione concentration in mammalian seminal plasma does not exceed 2 pM/mL. In
human seminal plasma the concentration is about 55 pg/mL [2]. In addition, the intracellular
concentration of glutathione in human spermatozoa (13 nM/ lo6 spermatozoa) is apparently insig-
nificant if compared to the total content of the thiol groups (95-700 nM/106 spermatozoa). Even
at these low levels, glutathione could be involved in the antioxidant protection of the sperm cell
membrane during and after ejaculation. The presence in semen of two enzymes, glutathione
+ -
peroxidase (2GSH H20, GSSG + 2H20) and glutathione reductase NADPH (GSSG 2 -
GSH), constitutes a true glutathione cycle that provides an effective buffer-defense mechanism
against sperm membrane lipid peroxidation. This occurs in spermatids in rats [3]. Moreover,
lipid peroxidation potential (LPO,) has been used as a marker of sperm defense ability, whereas
reactive oxygen species (ROS) is indicative of sperm damage [l].
The data seem to indicate a possible therapeutic effect of glutathione in some cases of male
infertility. It is possible hat glutathione acts on post-testicular spermatozoa. The findings of
F
this study seem to justify extending this therapy to a wider group of patients. ROS and LPO,
should also be studied in this context because these factors could explain the metabolic effects
of glutathione.
68 A. Lenzi et al.

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mechanism in isolated round spermatides from rat. Int J Androl 13:26-38
4. Li TK (1975): The glutathione therapy and thiol compounds of mammalian spermatozoa and seminal plasma. Biol
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