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Effect of
protodioscin on the quantity and quality of sperms from males with
moderate
idiopathic oligozoospermia
K.M. Arsyad
Medical Biology Division of Andrology, University of Sriwijaya, Indonesia
(1996)
Medika 22 (8): 614-618 (1996)
SUMMARY
This study was conducted
to assess the effectiveness of a certain dosage and period of administration
of Libilov (protodioscin) on sperm quality and quantity in men with moderate
idiopathic oligozoospermia. This study also evaluated protodioscin's effect
on libido, erection, ejaculation and orgasm. Lastly, We also determined the
length of time that the beneficial effects of the treatment lasted after
administration of the preparation was stopped.
Our result showed that
oral Libilov treatment with the dose of 3 x 2 tablets per day for 60 days
could:
- increase sperm quantity
and quality in men diagnosed with moderate idiopathic oligozoospermia
- restore and enhance libido, erection, ejaculation, and orgasm of sexual
intercourse, as compared to before the treatment. This result was obtained
in more than 80% of the treated patients.
ABSTRACT
A couple is defined as
infertile if no conception results after one year of normal sexual practice
without contraception. The world prevalence of infertile couples is between
5-20%, with 10-20% of which is without medical basis or explanation.
Etiologically, such infertility could result from either the male partner,
the female partner, or both. Studies in Indonesia showed that the frequency
of infertility due to the male partner is between 34-60%.
This study was conducted
to assess the effectiveness of a certain dosage and period of administration
of Libilov™(protodioscin) on sperm quality and quantity of men with moderate
idiopathic oligozoospermia. This study also evaluated protodioscin's effect
on libido, erection , ejaculation and orgasm in males. Lastly, we also
determined how long the beneficial effect of the treatment lasted after the
treatment was stopped.
Our result showed that
protodioscin treatment with the dose of 3 x 2 tablets / day per oral
administration for 60 days could increase the sperm quality and quantity in
men diagnosed with moderate idiopathic oligozoospermia, restore and enhance
libido, erection, ejaculations and orgasms of sexual intercourse, as
compared to before the treatment. These results were found in over 80% of
the treated patients. Finally, we suggest that a further, more detailed
study be carried out to assess the effect of protodioscin on oligozoospermia
with other etiological factors, as well as its effects on the male
reproductive system.
INTRODUCTION
A couple is diagnosed
with infertility, if within one year of regular sexual practice without the
use of contraception, no successful fertilization leads to pregnancy. If
this constitutes the female's first attempt to achieve pregnancy, this
infertility can be classified as primary infertility. On the other hand, if
the female has been pregnant before, leading either to normal birth or
spontaneous abortion, or if the female has had ectopic pregnancies, then the
infertility is classified as secondary infertility (1).
According to the National
Survey of Family Growth (2) in 1982, the prevalence of infertile couples
that want to conceive reaches 14% in the United States, whereas world-wide
this number ranges from 5-20% (1,3). Approximately 10-20% of these
infertility cases have no known medical basis or etiology, and can be due to
infertility in the male partner, the female partner, or both.
Barten and Moningka (4)
reported that based on a study conducted in Northern Sulawesi, Indonesia,
male infertility contributed up to 34% of the infertility cases.
Koesoemonegoro, however, suggested that in couples diagnosed with primary
infertility, infertile males made up 74% of the cases, whereas 60% of
secondary infertility cases were attributable to the males (5). Previously,
we determined that in 246 infertile couples in Palembang, Indonesia,
48% of their infertilities were due to the male partners (6).
Etiological studies of
male infertility is mostly based on laboratory analyses of semen. For
example, oligozoospermia can be caused by cryptorchidism, varicocele,
hydrocele, medication side effects, systemic infection, partial obstruction
of the vas deferens, or other idiopathic factors (Table I). In addition to
semen analyses, spermiogram and testes volume measurements are also often
used to diagnose male infertility.
|
Nomenclature
|
Testes Volume (ml) |
|
30-15 ml |
15-12 ml |
<10 ml |
|
Severe oligozoospermia |
Idopathic hypospermatogenesis Orchitism
Varicocele
Cryptorcidism
|
|
Moderate oligozoospermia |
Idiopathic hypospermatogenesis
Varicocele
Infection
Chronic disease
|
|
Asthenozoospermia |
Infection, varicocele,
immunological disorder,
accessory glands dis-
order, absence of dynein
arms |
Table I.
Etiology of male infertility based on spermiogram and testes volume analyses
(Hudson et al., 1980)
The current treatments
for oligozoospermia include medication by clomifen citrate, tamoxifen,
protodioscin, combination of HMG and hCG, combination of FSH and hCG, and
artificial insemination with or without treated sperms (8, 9, 10).
Protodioscin is the
dominant compound, present at no less than 45% of the total plant extract of
Tribulus terrestris L. It has been reported to increase spermatozoa
concentration, mobility as well as to improve libido in men and laboratory
animals (10, 11, 12). As protodioscin is a non-hormonal and non-synthetic
preparation that differed from other treatment options for oligozoospermia,
we sought to determine its effectiveness on the sperm quantity and quality
in males diagnosed with moderate idiopathic oligozoospermia. We also sought
to determine how long the beneficial effects lasted after treatment was
stopped. Lastly, we also determined protodioscin's effects on the male sex
drive, penile erection, ejaculation and orgasm qualities.
METHODS
This study was conducted
in six months, and involved 15 men diagnosed with moderate idiopathic oligozoospermia (7) of ages 25 to 40 years. We determined the following
variables before and after treatment:
- spermiogram
- FSH, LH and testosterone levels
- hematological analyses
- blood chemistry analyses
- testes volume by orchidometer
- sex drive, erection, ejaculation and orgasm qualities
Each patients received
protodioscin (Libilov) at a dose of 3 x 2 tablets / day orally for 60 days.
Semen analyses were performed twice before treatment (day 1), once after
treatment is concluded day 60) and once 30 days post-treatment (day 90).
Changes in sex drive or libido, erection, ejaculation and orgasm qualities
during sexual intercourse were measured by patient interviews at
mid-treatment (day 30) and after treatment (day 60). Data gathered were
subjected to statistical analyses (t-pair test), and was presented as means
± standard deviation.
RESULT AND DISCUSSION
As seen in Table II,
spermatozoa concentration increased in all patients, to approximately 160%
after treatment was over (day 60). This continued to increase to 200% when
tested 30 days after the last day of administration of protodioscin (day
90). Our result agreed with that previously published by Moeloek et al. (10)
and by Viktorof et al. (12). Moeloek reported that treatment of male
patients diagnosed with oligozoospermia with protodioscin at 3 x 2 tablets /
day dosage for 9 weeks resulted in increased sperm concentration.
|
Parameter |
Before Treatment |
After Treatment |
Without Treatment |
|
Sperm concentration (million/ml) |
9.89 ± 3.58 |
15.73 ± 3.41 |
18.40 ± 3.69 |
|
Mobility (a+b) (%) |
24.33 ± 7.03 |
36.00 ± 6.32 |
40.67 ± 6.51 |
|
Normal morphology (%) |
35.93 ± 4.03 |
43.87 ± 4.12 |
46.80 ± 5.18 |
Table II.
Sperm concentration, mobility (a+b), and with normal morphology before,
after, and without Libilov (protodioscin) treatment
In addition to the
increase in sperm concentration, we also discovered that the percent
mobility (grade a+b) and percentage of sperm with normal morphology were
also increased. This was different than that reported by Moeloek et al.
(10), which stated that although sperm morphology was improved, there was no
significant change in sperm motility.
The increase in sperm
concentration, mobility and morphology after treatment in this study is
statistically significant (p < 0.05). Even so, these improvements are still
not yet within the bounds of normal parameters as determined by the World
Health Organization in 1992 (13), i.e. > 20 million sperms / ml and percent
mobility (a+b) > 50%.
Coupled with hormonal
analyses (Table III), the increase in sperm mobility and morphology appeared
to be linked to the increased level of testosterone. Testosterone is
involved in sperm maturation in the epididymis (7, 14, 15). These findings
agree with the hypothesized mechanism of protodioscin, i.e. to increase the
efficiency of spermatogenesis and the increase in sperm production by
stimulation of the Sertoli and germinal cells. Protodioscin increases the
level of conversion of testosterone to dihydrotestosterone, which stimulates
the epididymal maturation of spermatozoa into fertile sperms (7, 11, 15).
|
Hormone Name |
Concentration |
|
Before treatment |
Day 30 |
Day 60 |
Normal Level |
|
FSH (IU/l) |
2.52 ± 0.33 |
2.16 ± 0.13 |
1.77 ± 0.16 |
1 - 12 |
|
LH (IU/l) |
6.86 ± 0.80 |
9.90 ± 2.10 |
7.10 ± 1.28
|
2 - 12 |
|
Testosterone (nmol/l) |
283.4 ± 24.7 |
328.4 ± 16.7 |
379.0 ± 89.7 |
270 - 1070 |
Table III.
Serum level of FSH (IU/l), LH (IU/l), and testosterone (nmol/l) before and
after 30 & 60 days of Libilov treatment
We concluded that the
level of FSH was not increased by protodioscin treatment (Table III). The
level of LH and testosterone, however, were increased to level still
accepted as normal. This result was internally consistent, as the increased
level of LH was responsible for the activation of Leydig cells to increase
testosterone secretion, thus resulting in increased testosterone level in
the bloodstream. This agreed with the previously described effect of
protodioscin on these hormones (11).
Although there was an
increase in the concentration of spermatozoa by protodioscin treatment, we
found no increase in the testes volume of treated patients (Table IV). This
could be due to our orchidometer, which had a set volume measurement of 1,
2, 3, 4, 5, 6, 8, 10, 12, 15, 20, 25, and 30 ml. An increase of 1, 2 or 3 ml
could not be measured in testes of more than 10 ml volumes. Moreover, it was
known that protodioscin does not increase the density of Leydig cells.
Instead, it increased the density of the Sertoli cells, and increased the
amount of spermatogonias, spermatocytes and spermatids without changing in
the diameter of the seminiferous tubules. In this study, the testes volumes
of the treated patients were categorized as either borderline (12-15 ml) or
normal (15-30 ml), according to the criteria set forth by Hudson et al. (7).
Patient Code
|
Before Treatment
left right
|
After Treatment
left right
|
S01
S02
S03
S04
S05
S06
S07
S08
S09
S10
S11
S12
S13
S14
S15
|
15 20
20 20
15 15
15 15
15 15
15 15
15 15
15 12
12 12
15 15
20 15
15 12
15 12
15 12
15 15
|
15 20
20 20
15 15
15 15
15 15
15 15
15 15
15 12
12 12
15 15
20 15
15 12
15 12
15 12
15 15
|
Table IV.
Testes volume (ml) before and after Libilov treatment
In Table V and Graph I,
we showed that the protodioscin treatment resulted in significant increase
in sex drive by 33% after 30 day of treatment, and continued to 80% after 60
days. Erection increased by 53% in 30 days, and by 87% in 60 days.
Ejaculation quality improved by 47% and 67% after 30 and 60 days of
treatment, respectively. Importantly, orgasm quality improved significantly
by 40% and 87% after 30, and 60 days of treatment.
|
Parameter |
Increased |
Remained the same |
Decreased |
|
Day 30 Day 60 |
Day 30 Day 60 |
Day 30 Day 60 |
|
Sex drive |
5(33%) 12(80%) |
10(67%) 3(20%) |
0 0 |
|
Erection |
8(53%) 13(87%) |
7(47%) 2(13%) |
0 0 |
|
Ejaculation |
7(47%) 10(67%) |
8(53%) 5(33%) |
0 0 |
|
Orgasm quality |
6(40%) 13(87%) |
9(60%) 2(13%) |
0 0 |
Table V.
Parameter of sexual fitness (sex drive, erection, ejaculation and quality of
orgasm or pleasure) before, after 30-, and 60-days of Libilov treatment.

Graph I.
Sexual fitness after 30- and 60-days of Libilov treatment
These result agreed
partially with a previous study (16), which reported improvement in libido,
although not a significant increases in the qualities of penis erection,
ejaculation and orgasm. As with all previous studies, no patients reported
any unwanted side-effects in this trial.
To determine whether
protodioscin treatment affected the normal heart and liver function, we
conducted a laboratory analyses to determine the Hb, hematocrit, thrombocyte
and lipid serum levels, as well as heart functions (Table VI). We concluded
that there were no abnormal or significant changes in these parameters. This
suggested that the administration of protodioscin for 60 days at 3 x 2
tablets / day was medically safe. The increase in the Hb level seemed to be
due to the increased conversion of to dihydrotestosterone.
Dihydrotestosterone, a potent androgen, stimulated erythropoesis and muscle
developments. This contributed to a general feeling of well-being and health
reported by some patients, as increased red blood cells level improved
oxygen transport and circulation in the body. These, in turn, would also
contribute to the improvement in sexual functions of the patients, in all
part of the sexual response phases (17).
|
Parameter |
Result |
|
Before |
Day 30 |
Day 60 |
Normal |
|
Hematological
Hb (g/100ml)
Hematocrit (%)
Thrombocyte(million/ml) |
13.3 ± 0.5
40.4 ± 1.2
201.2 ± 50.5 |
13.6 ± 0.5
41.8 ± 1.8
198.8 ± 41.6 |
14.7 ± 0.7
42.5 ± 1.5
247.1 ± 47.0 |
12 - 18
45 - 62
150 - 300 |
|
Lipid/Enzyme
SGOT(IU/l)
SGPT (IU/l)
Gamma GT (IU/l)
Alkaline phosphatase (IU/l)
Total cholesterol (mg/100ml)
HDL (mg/100ml)
LDL (mg/100ml)
Triglyceride (mg/100ml) |
22.1 ± 11.7
20.2 ± 9.7
21.5 ± 3.6
44.2 ± 7.1
183.5 ± 12.8
35.8 ± 14.1
126.4 ± 18.8
114.7 ± 34.4 |
10.6 ± 6.2
14.8 ± 4.0
10.6 ± 4.9
86.1 ± 7.2
178.8 ± 24.3
35.3 ± 7.8
110.6 ± 24.9
108.8 ± 16.2 |
24.0 ± 4.9
20.6 ± 4.0
11.5 ± 3.8
78.6 ± 3.0
175.1 ± 30.3
41.1 ± 9.5
119.1 ± 26.1
93.0 ± 29.9 |
10 - 40
6.3 - 22
6 - 26
36 - 92
130 - 270
30 - 60
70 - 190
72 - 174 |
Table VI.
Hb, hematocrit, thrombocyte and lipid serum levels; and heart functions
SUMMARY AND SUGGESTION
Based on our study, we
concluded that protodioscin treatment for 60 days at the dose of 3 x 2
tablets per day could create improvements in the quality and quantity of
sperms, in sex drive, erection, ejaculation and orgasm qualities in treated
males. Significantly, improvements in sex drive were experienced by 80% of
males. A more detailed further study, however is warranted to determine the
efficiency of protodioscin treatment on other forms of oilgozoospermia, and
to determine in detail its effect on the male reproductive system.
ACKNOWLEDGEMENT
We wish to thank PT
Teguhsindo Lestaritama for providing protodioscin (Libilov™) for this study.
REFERENCES
1. World Health
Organization Guidelines on Diagnosis and Treatment of Infertility (1989).
2. Suoles, M.R.
Prevention of Infertility. Fertil. Steril. 49:582-584 (1988).
3. El Badawi, M.A.
Effects of Occupational Health Hazard on Reproductive Function. WHO, Geneva
p. 8-127 (1987).
4. Barten, J., Moningka,
B.W. The Male Factor Infertility in Suhadi, K. (ed) Spermatology, PANDI,
Surabaya, p. 292-297 (1978).
5. Koesoemonegoro, S. The
Male Factor in Couple's Infertility in Suhadi, K. (ed) Spermatology, PANDI,
Surabaya, p. 192-210 (1978).
6. Arsyad, K.M.
Infertility Diagnoses in 246 Infertile Couples. PIT PANDI VII, Palembang
(1989).
7. Hudson, B., Baker, H.W.,
and deKretser, D.M. The Abnormal Semen Sample in Pepperel, Hudson, Wood
Churchill and Livingstone (eds) Infertile Couples, p. 70-111, Edinburg
(1980).
8. Adimoelja, A. The Male
Infertility Therapy and Contraception. PIT PANDI VIII, Padang (1990).
9. Isidory, A. Update on
Hormonal Control on Spermatogenesis: Central and Peripheral Factors.
Workshop on the Treatment of Male Infertility and Male Reproductive
Disorders, Jakarta (1991).
10. Moeloek, N.,
Adimoelja, A., Tonojo, T., and Pangkahila, W. Trials of Tribulus terrestris
on oligozoospermia. National Congress of Indonesian Association of Andrologs
Scientific Meeting VI,
Manado
(1994).
11. IIMS Therapeutic Focus. Vol. 2 (1994).
12. Viktorof, I.V.,
Kolayanov, A.L., Lilov, L., and Zlatanova, V. Clinical Investigation of
Tribestan in Males with Sexual Function Disorders. MBI, Bulgaria (1981).
13. World Health
Organization Laboratory Manual for the Examination of Human Semen and
Sperm-Cervical Mucus Interaction 3rd ed. Cambridge University Press,
Cambridge (1992)
14. Hellinga, G. Clinical
Andrology, William Heinemen Medical Book Ltd., London (1976).
15. Greenspan, F.S. Basic
and Clinical Endocrinology 3rd ed. p. 407-442. Appleton & Lange, Northwalk
(1991).
16. Pangkahila, W. Libilov increases men's sex drive. National Congress of
Indonesian Association of Andrologs Scientific Meeting X, Denpasar (1993).
17. Kolodny, R.C.,
Masters, W.H., and Johnson, V.E. Textbook of Sexual Medicine. p. 1-27.
Little Brown and Co., Boston (1979).
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