(protodioscin) in the treatment of male infertility with idiopathic
A Adimoelja, L Setiawan, and T Djojotananjo
Academic Hospital Dr. Soetomo and Airlangga University, Surabaya,
in First International Conference of Medical Plants for Reproductive
Medicine in Taipei, Taiwan (1995)
Tribulus terrestris L (TTL) extract is a natural remedy that has
been successfully tested clinically for its use in the treatment
of idiopathic oligoasthenoteratozoospermia (OTA). Here, we conducted
a double blind study of 45 infertile, married men with OTA. 36 men
were treated with 500 mg purified TTL (Libilov) 3 times daily for
3 months. Composing the controlled group, 9 men were given placebo
(sugar pills) for the same period of time. Spouses of 8 of the men
in the treated group successfully achieved pregnancies after treatment
of their husbands, whereas no pregnancies occurred in the spouses
of the men in the control group. An improvement in the sperm morphology,
including that observed under conventional phase contrast microscopy
as well as improvements in acrosome morphology and reaction, seemed
to account for the increased fertility after treatment. In addition,
TTL was also shown to increase the level of dehydroepiandrosterone
(DHEA) and might also contributed to the activation of cell membrane
receptors and the production of weak androgens. These, in turn,
might additionally improve fertility by increasing the level of
Recently, herbal remedies have became popular in many Eastern as
well as Western countries. Many of the active ingredients of these
remedies have been successfully purified and standardized, resulting
in a diversity of various extracts known as pythochemicals. Tribulus
terrestris L (TTL) is one of such herbal remedies that have been
successfully tested clinically for its use in the treatment of idiopathic
oligoasthenoteratozoospermia (OTA) in male subjects. In this double
blind study, 45 infertile married men with OTA were recruited. Thirty
six men were treated with 500 mg purified TTL (Libilov) 3 times
daily for 3 months. 9 men were given sugar pills (placebo) to compose
the control group for the same period of treatment. Spouses of 8
men in the treated group achieved pregnancies after treatment, whereas
no spouse of the males in the control group did. No significant
differences (p > 0.05) in liver and kidney function tests, as
well as serum sex hormone levels (FSH, LH, PRL, T) were reported
before and after treatment. The results of the semen analyses done
before and after treatment of both the control and the treated groups,
however, showed a significant increase in sperm concentration. Hence,
the increased sperm concentration did not seem to contribute to
the successful pregnancies. No improvement of sperm motility were
observed between the two groups. There was, however, improvement
in sperm morphology in the treated group (p > 0.05), which could
explain the successful pregnancies in this group. Better sperm morphology
was observed microscopically by the conventional phase contrast
procedure. TTL seemed to improve the acrosome morphology of the
sperm cells and enhanced the acrosome reaction, thus contributing
to increased fertility. The active component of TTL, termed protodioscin,
was shown to increase the level of dehydroepiandrosterone (DHEA),
and might also have contributed to the activation of cell membrane
receptors and the activation of weak androgens, thus contributing
to increased spermatogenesis and fertility.
In the late 20th century, herbal medicines became more popular,
especially after scientific and pharmacological efforts to identify
active components were able to introduce standardization to this
field. This contributed very much to our understanding of the role
of the natural bioactive phytochemical components in traditional
herbal medicines in benefiting human health and in understanding
its possible side-effects as well.
Tribulus terrestris L (TTL) is one such herbal remedy that has
recently been scientifically studied, purified, standardized and
clinically tested for its usefulness or benefits in treating male
infertility due to oligoasthenozoospermia (Protich et al. 1984).
The Tribulus plant has long been used as herbal remedies in Eastern
European and Asian countries to treat sexual disorders, such as
impotence or to treat infertility. Recent scientific research identified
the active ingredient of TTL extracts as a non-steroidal furostanol
saponin, which constituted 45% or more of the purified extract (Zarkova
Recently, the purified dry powder of TTL, in form of a tablet preparation,
has been studied in a multi-center study in Indonesia for treatment
of infertile males diagnosed with idiopathic oligoasthenoteratozoospermia
(OTA) (Moeloek et al. 1994). The active ingredient of TTL extracts
has received approval by the Indonesian Food and Drugs Administration
(POM), and is marketed under the name of Libilov™. A total
of 45 subjects were involved in this study: 36 of which were treated
and 9 of which were given placebo for the entire duration of the
study. After 3 months, eight (22%) of the infertile male subjects
in the treated group succeeded in impregnating their spouses, whereas
no subjects in the control group did.
Semen analyses were conducted to determine the factor or factors
responsible for the increased fertility of the treated group, as
compared to the control group. There was no significant difference
in conventional laboratory sperm analyses in both groups before
and after treatment. Significant improvements in sperm concentration,
however, were observed for both the treated and the control groups.
Although this was a significant benefit, as sperm concentration
also increased in the control group, we concluded that this could
not be the reason for the successful conception of the spouses of
the male subjects in the treated group. Preliminary data suggested
that improved sperm morphology, specifically improved acrosome reaction,
might be the responsible factor. We are currently conducting further
research efforts to identify factors responsible for the increased
fertility of the treated group.
SUBJECTS AND METHODS
Six subjects from the Libilov treated group who had successfully
impregnated their spouses, six other subjects taken randomly from
the treated group, and six subjects from the control group were
subjected to laboratory semen analyses. In vitro sperm-cervical
mucus interaction test and in vivo post-coital test were conducted
(WHO 1987). Preliminary study on sperm acrosome morphology was performed
by the acrosin staining method (Pedersen, 1976; Schill 1976).
Better penetration was observed in sperms from the treated group,
which consisted of subjects that successfully or unsuccessfully
impregnated their spouses, as compared to that of the control group.
However, no significant differences were observed in sperm samples
from within the treated groups, i.e. between those who were successful
in impregnating their spouses as compared to those who were not.
Post-coital tests performed also suggested improvements in the
treated group as compared to the control group. There was, however,
no significant difference between those who successfully impregnated
their spouses and those who did not.
Acrosin staining revealed a significant increase in the percentage
of normal acrosomes in sperms from the treated subjects who succeeded
in impregnating their spouses. In contrast, no increase was observed
in sperms from both the control group subjects or from the treated
subjects who were not successful in achieving pregnancy in their
DISCUSSION AND CONCLUSION
The clinical study described in this paper resulted in successful
fertilization in 22% of subjects that took part as the treated group.
Detailed analyses of the sperm from the treated and control groups
revealed that there were significant improvements in sperm morphology,
especially the acrosome reaction, but no significant differences
in sperm concentration or motility. The improved sperm-cervical
mucus interaction and improvements measured by the post-coital test
suggested that the increased acrosome reaction led to the improved
sperm functions, thus resulting in successful conception. A further
study on the effect of TTL treatment on acrosome reaction is currently
The chemical structure of protodioscin is very similar to that
of dehydroepiandrosterone (DHEA), one of the most important hormones
in the body. We speculate that protodioscin can stimulate the production
of DHEA, or can serve as a non-hormonal precursor to DHEA. Protodioscin-stimulation
of DHEA levels can also contribute to increased fertility, as DHEA
has been reported in several studies to be important in the process
of sperm maturation in the epididymis. Furthermore, the conversion
of DHEA to testosterone or dihydrotestosterone, both potent androgens
or sex hormones important for spermatogenesis in the seminiferous
tubules, can also contribute to increased fertility. A better understanding
of the function of DHEA in general health, and specifically in the
male reproduction and sexual functions, is therefore also important
to our understanding of infertility and its treatment.
Gaby AR (1993). DHEA: The hormone that "does it all".
Holistic Medicine. pp. 19-24. Hafez ESE and Prasad MRN (1976). Functional
aspects of the epididymis. In Human Semen and Fertility Regulation
in Men. Pp. 31-43. ESE Hafez editor. The CV Mosby Company, St. Louis.
Moeloek N, Adimoelja A, Tanojo T, Pangkahila W (1994). Trials of
Tribulus terrestris on oligozoospermia. Proceedings of the VIth
National Congress and IIIrd International Symposium on New Perspectives
on Andrology in Human Reproduction. National Congress of Indonesian
Association of Andrology (PANDI) in Manado, Indonesia.
Pedersen H (1976). Functional anatomy of the human spermatozoon.
In Human Semen and Fertility Regulation in Men. Pp. 65-75. ESE Hafez
editor. The CV Mosby Company, St. Louis.
Protich M, Tsvetkov D, Nalbanski B, Stanislavov R, Katsarova M
(1994). IIMS Therapeutic Focus.
Schill WB (1976). Acrosin activity in human sperm. In Human Semen
and Fertility Regulation in Men. Pp. 217 - 227. ESE Hafez editor.
The CV Mosby Company, St. Louis.
Zarkova S (1994). IIMS Therapeutic Focus.
World Health Organization (1987). Laboratory manual for the examination
of human semen and semen-cervical mucus interaction. WHO, Cambridge
University Press, Cambridge.