Tribex Article

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INTRODUCTION
The problem of stimulation of sexual function of the animal organism, stimulation of spermatogenesis and ovogenesis in particular, has a general biological and medical significance since it is associated with the problem of preserving the sexual potential of male and female individuals. According to summed up statistics, 10 - 20 per cent of all marriages are childless. In about 30 - 50 per cent of them the cause of infertility is to be related to the male. Diagnostics and treatment of male infertility is still a difficult task.
Hormonal preparations are at present prevailing in the treatment of sexual deficiency and anomalies. In fact, substitutional hormonal treatment is temporary, sometimes non-effective, very often extending hypofunction of the hypothalamushypophyseal-gonadal axis. Hence, in spite of a great number of new, highly efficient and possibly less noxious drugs - research in this field is very actual. The development of non-hormonal preparation, sufficiently active and without harmful side effects would contribute to overcome sexual functional disorders.

The Tribulus terrestris L., has long been a quite popular medicinal herb in folk medicine of the Eastern peoples and Bulgaria in the treatment of sexual deficiency. Based on those data, an original phytochemical preparation, Tribex, with a stimulating effect on sexual functions has been developed and approved for production and use in medical practice at Pharmachim’s Chemical Pharmaceutical Research Institute, (1981).

The present booklet is intended to acquaint the reader with the pharmacological, toxicological and clinical-therapeutic characteristics of the preparation.




GENERAL INFORMATION ON TRIBEX

Tribex is an original non-hormonal preparation. Active components are steroid saponins of the furostanol type, isolated from the plant Tribulus terrestris L.
Oral administration of the preparation to sexually mature rats disclosed a marked stimulating effect on spermatogenesis. It increases the number of spermatogonia, spermatocytes, spermatids and mature spermatozoa in the testis, without increasing the diameter of the seminiferous tubules. Parallel to this an increased number (density) of Sertoli’s cells in the testis of the rat has been observed. Oral administration stimulates the miotonic activity of spermatogonia in the mature rat.

Oral administration of the preparation is followed by intensification of spermatogenesis, improvement of the quality of spermatozoa in sexually mature rats. It increases the percentage of motile spermatozoa, improving the characteristics of spermatozoa motility, extending at the same time the period of their survival.

Administered orally to male animals (boars), Tribex stimulates their sexual behavior.

Clinical trials with the preparation confirmed once more experimental data.

Tribex, administered to males with spermogram disturbances due to varicocele, increases the volume of ejaculated sperm by 1-2 ml, boosts the concentration of spermatozoa by 30 million/ml, raises the percentage of motile spermatozoa by 30.

The preparation has a pronounced effect on the motility of spermatozoa in cases of idiopathic oligoasthenozoospermia. Before treatment the number of motile spermatozoa for the group at trial disclosed a mean value of 29 percent, reaching after treatment - 36.6%. The speed of spermatozoa movement prior to treatment was 1.95m m/s, after treatment - 3.76m m/s.

Treatment of patients with unilateral and bilateral hypotrophy of the testes, accompanied by disturbances in the spermogram is of some interest. After a 60-day Tribex treatment the libido was enhanced and spermogram improved. In patients with primary and secondary hypogonadism, restored and enhanced libido was observed after Tribex treatment as well as improved and lengthened erection.

Experimental and clinical studies reveal that the preparation is not toxic and has no adverse side effects.




1. CHEMICAL AND PHYSICAL PROPERTIES

Tribex is an original preparation, produced at the Chemical Pharmaceutical Institute in Sofia, Bulgaria*. The active components are steroid saponins of furostanol type, isolated from the plant Tribulus terrestris L. The preparation is standardized on the base of the predominating compound protodioscin - not less than 45%.


Synonyms - none.
Structural formulation of protodioscin:





The substance is a yellow-brown amorphous powder of a specific smell and bitter taste; water-soluble, not readily soluble in methyl alcohol, insoluble in chloroform.


2. PHARMACOLOGICAL STUDIES



2.1 METHODS CHARACTERIZING THE STIMULATING EFFECT ON SPERMATOGENESIS

Spermatogenesis is a complicated process, including the proliferation of spermatogonia, a long process of cellular divisions (meiosis) and numerous cytological changes in spermatids during their preformation. The effect on germinative cells could be realized during the reproductive period - mitotic division of spermatogonia or during the process of spermatocytes maturing.
The effect of the preparation on the division and maturing of germinative cells has been investigated by means of quantitative cytological methods. The testes of eight rats, orally treated with Tribex for 20 days (once daily with 70-mg/kg b.w.) were fixed in neutral formol-calcium and Serra’s solution and embedded in paraffin. The testes of eight intact animals were taken as controls. Histological sections were stained with hematoxylin (according to Mayer) and fast-green (according to Yordanov, 1976). The spermatogonia, spermatocytes and spermatids were counted in 40 transversal sections through the seminiferous tubules from each experimental and control animal (total 640) with identical diameter (determined by ocular micrometer), at stage VII, in accordance with the classification of Leblond and Clermont (1952). An increased germinative cells layer in the transversal sections through the seminiferous tubules as well as a reduction of their lumen were observed in the testes of the treated animals by means of light-microscopy. The increase was due to the rising number of rows of germinative cells (Fig. 1). Spermatogonia count in the eight experimental animals (on 320 sections through the seminiferous tubules) disclosed an average of 58 spermatogonia per seminiferous tubule with limits between a minimum 48 and maximum 63. The mean spermatogonia number per seminiferous tubule in the control animals was 36, within reference values of minimum 36 and maximum 40. The average number of pachytene spermatocytes in a section through the seminiferous tubule is identical with that of spermatogonia. The phase VII spermatids in the rats treated with the preparation varied from 148 to 180 per seminiferous tubule (mean value 176). The spermatids varied from 112 to 125 per seminiferous tubule in the control animals (a mean of 119). The preparation significantly increased the number of spermatogonia, spermatocytes and spermatids in the rat testis, without any effect on the diameter of the seminiferous tubules.




2.2 EFFECT ON DNA-SYNTHESIS IN GERMINATIVE CELLS

The effect on the preparation on DNA-synthesis in the germinative cells was studies with the aid of cytohistoradiography.
The testes of the rats, treated during 7 days with Tribex, every second day with 3H-thymidine, further with colchicine 3 hours prior to decapitation, were fixed in Serra’s solution and embedded in paraffin. The sections were covered with Ilford I4 liquid emulsion and exposed for 25 days. Results among the experimental rats revealed a greater number of 3H-thymidine-labelled spermatogonia "A" and "B" as compared with the controls (Fig. 2). The average number of spermatogonia in section through the seminiferous tubule was 56 in the experimental animals, 41 of them - labelled. An average of 50 spermatogonia per seminiferous tubule was found in the control animals, 18 out of them - labeled. Differences between experimental and control animals prove significant and disclose a considerable increase of spermatogonia in a s-period of the treated animals.





2.3 EFFECT ON LEYDIG AND SERTOLI CELLS OF THE TESTIS

Leydig and Sertoli cells are known to participate in the process of spermatogenesis. Quantitative cytological methods were applied in order to check the effect of the preparation on Leydig and Sertoli cells. The results revealed that compared with the controls, Sertoli cells in the seminiferous tubules, in Tribex-treated rats, are present in a greater density (Fig. 3).
The average number of Sertoli cells in a section through a seminiferous tubule of the experimental rats was 29, versus 19.50 in the controls (an increase of 40%). Cytological studies on the testes showed no differences in the number of Leydig cells in the experimental and control rats.




2.4 EFFECT ON CONCENTRATION, MOTILITY AND SURVIVAL OF SPERMATOZOA

Concentration, motility and survival of spermatozoa in the epididymis of the rats were studied immediately after decapitation. The animals were treated during 30 days with Tribex. Sodium citrate was used as a diluent. The average number of spermatozoa per ml, in the experimental animals, was higher - by two millions, compared to that of the controls (Fig. 4).
Motile spermatozoa, estimated under the microscope, proved by 8 per cent more in the experimental animals as compared with the controls. Furthermore, the spermatozoa of the experimental animals were more viable and resistant. Loss of their propulsive movements were observed by the 75th minute, compared to the control animals - by the 45th min. (Fig. 5).





2.5 EFFECT ON LIBIDO SEXUALIS

The effect of Tribex on sexual behavior was studied on boars, with established prolonged sexual impotence. The preparation was orally administered and its effects on libido sexualis and the course of sexual reflexes were daily checked during the treatment.
The results revealed among the boards individual reactions to the preparation. In boars, with absolute absence of libido, treated with a daily dose of 70 mg/kg during 10 days, libido and sexual reflexes were restored in 71 percent of the animals. Among boars wit poor libido and prolonged reflex time for sexual reflexes, recovery was observed in 100 percent of the treated animals (Fig. 6).






2.6 STUDIES ON SERUM CONCENTRATION OF THE HORMONES FROM THE HYPOPHYSEAL-GONADAL AXIS

The experiments were carried out on healthy subjects (8 males and 8 females), aged between 28 and 45 (Milanov et al. 1981). The preparation was orally administered, one tablet three times daily at equal intervals for 5 days. Basal levels of hormones, before and after treatment (at 8 and 12 o’clock) were estimated. Luteinizing (LH) and foliclestimulating (FHS) hormones were determined according to A.R. Midgley (1967) be means of kits, supplied by Biodata (Italy). Testosterone was determined according to B.H. Williams’ method (1968), estradiol - according to C.P. Orezyk (1974) with the aid of kits, supplied by Sorin (Belgium). Results disclose that the preparation, orally administered to healthy males, increased the level of luteinizing hormone and testosterone. FSH was not affected (Fig. 7).



Among women, the concentration of FSH and estradiol was increased by the preparation, testosterone being very slightly influenced (Fig. 8). Results reveal that the preparation has an effect on the hormones from the hypophyseal-gonadal axis, at the same time not disturbing the hormonal balance in organism, thus permitting to be applied as stimulating agent of the reproductive function.





2.7 EFFECT ON THE CENTRAL NERVOUS SYSTEM

Studies were carried out in accordance with the screening-system for neuropharmacological investigations (R. Nikolov, 1980). The following parameters were checked at the first stage screening: consciousness, mood, motor activity, muscular tone and somatic reflexes of the experimental animals.
The second stage of screening included interaction with many substances with a central effect, i.e. corazol, strychnine, nicotine, arecoline, phenamin, hexabarbitalsodium, rezerpin. The preparation was intraperitoneally administered to albino mice, line H, body weight 18-22 g.

The preparation in a dose of 100 mg/kg b.w. (1/4 LD50), has no effect on the behavior of intact animals in a cage. When observed outside the cage, the animals became excited, with enhanced reactivity. Their muscular tone was at the same time diminished. Under the same dose the preparation moderately inhibited corazol convulsions, the remaining reflexes being reduced. The maximum tolerable dose of 300 mg/kg b.w. led to reduced motor activity, slight disturbances in gait and diminished muscular tone of the limbs and abdomen. The whiskers reflex disappeared, the remaining reflexes proved diminished.



2.8 EFFECT ON THE CARDIOVASCULAR SYSTEM

Effect on blood pressure was studied in accordance with Ludwig Zyon’s method on cats under urethane narcosis (S. Vankov, 1981). The preparation was intramuscularly and intraperitoneally administered in the form of 10% aqueous solution. An intramuscular administration of the preparation in doses 50, 100 and 150 mg/kg b.w. did not essentially influence the blood pressure of urethanized cats. Under intraperitoneal administration in a dose of 150 mg/kg b.w. to urethanized cats, a considerable hypotensive effect was observed, advancing 5 to 10 minutes after administration, of the order 20 per cent of the initial level. Orally administered to awake dogs, in a dose of 150 mg/kg b.w. Tribex had no effect on the blood pressure. Its oral administration in a dose of 50, 100 and 150 mg/kg b.w. had no effect on the functional state of the autonomic nervous system of urethanized cats.


2.9 PHARMACOKINETIC STUDIES

The experiments were carried out on albino Wistar rats (1800-200 g b.w.) by N. Dikova and V. Ognyanova, 1981.
Estimation of unaltered protodioscin in plasma, bile and urine was carried out with the aid of thin-layer chromatography. Semi-quantitative determinations were carried out standardized with precisely determined protodioscin concentrations. For the determination of the plasma protodioscin concentrations, the animals were injected intravenously with a single dose of 50 and 200 mg/kg b.w. Citrate blood was withdrawn at 2, 4, 10, 20, 30, 45, 60, 90, 120 and 180 minute after the injection. For the determination of protodioscin excretion in the bile, the animals were intravenously and orally treated with single doses of 50 and 200 mg/kg. The bile was dynamically collected - by the 6th hour, from 6-9th hour, from 9-24th hour after a single intake. Twenty-four hour urine was collected. The results revealed that protodioscin was quickly eliminated from the plasma, its concentration being negligible by the 180th minute. Within 24 hours, about 12 and 14 per cent of protodioscin was excreted in the bile, about 6 and 7 per cent in urine according to the doses of 50 and 200 mg/kg b.w. after intravenous administration.

Under oral administration 2 to 4 per cent protodioscin was excreted in the bile. No measurable concentrations of unaltered protodioscin were established in 24-hour urine after oral administration.



2.10 TOXICOLOGICAL STUDIES



2.10.1 ACUTE TOXICITY

Acute toxicity of Tribex was tested on albino mice, line H, (18-20 g b.w.) and albino Wistar rats (180 - 200 g b.w.) intraperitoneally and orally administered, by the assessment of LD50.
It was established that the preparation is to be included in the group of practically non-toxic substances. LD50 with the intraperitoneal administration to mice is 1942 mg/kg b.w., orally - over 10,000 mg/kg b.w. In rats the mean lethal Tribex dose under intraperitoneal administration is 750 (375 ± 1,500) mg/kg b.w., and orally - over 10,00 mg/kg.



2.10.2 SUBCHRONIC TOXICITY

The preparation was orally administered to albino Wistar rats for 30 to 90 days in the following doses: 75 mg/kg, 150 mg/kg, 225 mg/kg and 300 mg/kg b.w. No lethality or change of behavior was observed among the animals. No substantial changes in routine clinical-laboratory and biochemical indices, further no morphological changes in the internal organs were established.


2.10.3 CHRONIC TOXICITY

Tribex was orally administered to albino rats in the course of 6 months in doses of 75 mg/kg b.w. and 150 mg/kg b.w. "Beagle" dogs were orally treated with 75 mg/kg b.w. for 180 days. The following toxic manifestations were looked for: changes in behavior further in hematological, biochemical, functional and morphological parameters. No essential changes were established in the behavior and the reflexes of the animals. No lethality was recorded. No pathological deviations from the physiological values of all the hematological and clinical-chemical indices were established as well as no pathological changes in the structure of the internal organs under investigation attributed to the toxic effect of the preparation.
At the same time, teratological and embryotoxic studies were carried out as well as some experiments for the follow-up of pre- and postnatal development of the new progenies (Z. Ilieva, 1980).

Administered by mouth in a dose of 750 mg/kg b.w. on pregnant Wistar rats, the preparation hand no teratogenic and embryotoxic effect as well as deleterious effect on the postnatal development of the first progeny.

Studies were carried out in relation to an eventual oncogenetic potential of Tribex on rats under long-term treatment (Genadjev, 1981).

The preparation, under oral doses of 50 and 150 mg/kg b.w. for 23 months, did not increase the number of neoplasms as compared with the control animals and induced no morphologically detectable toxic lesions of the organs of the rat.



2.11 DISCUSSION OF THE RESULTS

Experimental data on the biological activity of Tribex reveal that oral administration to experimental animals (rats) significantly increases the number of spermatogonia, spermatocytes and spermatids in the testis of the treated animals, without changing the diameter of the seminiferous tubules. This is to be related to a manifested stimulating effect on spermatogenesis as a whole - division and maturing of germinative cells. It is well known that DNA-synthesis (reduplication of chromosomes) is realized in the mitotic cycle (s-period), followed by cell division. The fact that Tribex- and 3H-thymidine-treated rats show a considerable increase in the number of spermatogonia type "A" and "B", found during the s-period, compared to the control animals - is of particular interest.
It could therefore be concluded that the preparation enhances the mitotic activity of spermatogonia. The increase of Sertoli’s cells under the effect of the preparation, cytologically established, suggests that the division of Sertoli’s cells have also been stimulated. The important role ascribed to these cells, in relation to the regulation of spermatogenesis is well known (Lacy, 1967, Kerr and de Krester, 1974; Steinberger, 1971), hence the increased number of Sertoli’s cells, under the effect of Tribex should be associated with an intensified spermatogenesis.

No changes were observed in interstitial (Leydig’s cells) in the testes of experimental rats, suggesting that the effect of the preparation on spermatogenesis, very likely, bypasses these cells (Leydig). Data in the literature disclose that proliferation of spermatogonia in mammalia and birds is being stimulated by FSH (Steinberger et al., 1964; Mancini et al., 1966, Ishii S. and Tribulus terrestris L. Furua, 1975; Krueger et al., 1974). The authors suggest that FSH effect on spermatogenesis is being realized by Sertoli’s cells. Radioimmunological studies on healthy male subjects revealed no FSH changes under the effect of Tribex. That provided grounds to assume a certain selective effect of the preparation on the germinative cells. On the other hand, increased LH was also radioimmunologically established in healthy, Tribex-treated male subjects, suggesting a central effect.

Pharmacokinetic studies reveal that under oral administration, no plasma levels are being reached in rats, and chromatographycally - some other non-identified so far spots were established. The authors (Dikova and Ognyanova) assume that biotransformation develops in the organism. It would be expected, in such cases, that some of the metabolites, formed during the biotransformation, have a stimulating effect at a hypothalamic level.

Results relating to libido sexualis in boars are distinctly manifested. Tribex not only stimulated reduced libido but also had a therapeutic effect in cases with sexual impotence, accompanied by complete absence of libido. Data delineating the effect on the quality of spermatozoa convincingly suggest that spermatozoa in experimental animals treated with Tribex are more energetic, more resistant, assuming a better fertilizing ability. The greater part of researchers is of the opinion that sexual behavior and motility of spermatozoa depend on testosterone. Some other authors think that sexual behavior is due to dehydrotestosterone.

The problem, who and how, the sexual behavior is stimulated is still under discussion.

If we presume that androgen-like acting factors are being formed in the organism by biotransformation, they bould no induce changes in the interstitial cells.

The harmlessness of the preparation deserves particular attention. No data about toxic manifestations were established under experimental conditions with acute, subchronic and chronic toxicity (behavioral, hematological, biochemical, functional and morphological studies). No data were established concerning carcinogenetic and teratogenetic effect.

Equally important is the fact that the preparation intervenes in the hormonal regulation in organism, without disturbing its functional mechanisms.

The combined action of the preparation (stimulation of sexual behavior and spermatogenesis) and the absence of adverse effects characterize the preparation as an original agent for the treatment of males with disorders in the sexual function.



3. CLINICAL STUDIES IN MALES



3.1 MATERIALS AND METHODS

Experimental data on Tribex were confirmed clinically by three teams so far: Higher Military Medical Institute - under the direction of Prof. Iv. Viktorov, Corresponding Member of the Bulgarian Academy of Sciences; Medical Academy - Institute of Endocrinology, Gerontology and Geriatrics - under the direction of Prof. E. Bozadjieva and Medical Academy - Institute of Obstetrics and Gynecology - under the direction of Dr. M. Protich.
The studies cover 212 males, aged between 14 and 60. Therapeutic Tribex properties were checked as regards impotentia, coeundi and generandi, its tolerance and side effects.

Investigations were carried out within a single blind test with placebo. As regards nosology, various types of male infertility were covered (idiopathic oligo-asthenozoospermia - 39 subjects, resection of the left internal testicular vein, due to varicocele with oligo-asthenozoospermia - 50 subjects, with inflammatory processes of prostate with oligo- and azoospermia - 53 subjects; primary and secondary male hypogonadism - 20 subjects; impotentia coeundi - 50 subjects).

The preparation was administered to all patients alone, and none of the patients was to receive hormonal preparations for at least a month before treatment. Duration of the treatment depended on the severity of the disease - 30-60 days on the average (Bozadjieva et al., Protich et al.) and 90 days (Viktorov et al.). the average daily dose was 3 - 6 film-tablets of 0.250 g. Some patients were influenced by 3 tablets (Protich et al.), whereas the remaining teams administered six tablets daily (3 x 2). The andrological state is the base for all three teams, for a proper assessment of the reproductive ability of the patients. The basic sperm parameters were checked, i.e. volume and pH of ejaculate, concentration of spermatozoa (number per 1 ml), percentage of motile spermatozoa, average speed of population movement, percentage of pathological spermatozoa forms. Detailed anamnestic data were collected about the sexual behavior of the patients, immediately before and after a therapeutic course with Tribex. The effect of the preparation on hairiness in some patients was followed up. One of the teams (Bozadjieva et al.) checked the changes in the serum levels of gonadotropins, progesterone, testosterone, estradiol and cholesterol under the effect of the preparation. The other team (Viktorov et al.) followed changes in the serum levels of testosterone in Tribex-treated patients. Hormone levels were determined radioimmunologically by means of kits of reagents supplied by the French-Italian-Belgian Association CEA-IRE-SORIN. Results from these investigations were statistically assessed with the aid of various analyses.



3.2 RESULTS

Significant changes were established in the motility of spermatozoa, in relation to the percentage of spermatozoa with normokinesis and hte average speed of movement, after 60 days Tribex treatment (with daily dose - three film-tablets) of males with idiopathic oligoasthenozoospermia. Percentage of motile spermatozoa before treatment was 29 on the average for the group, reaching after treatment 36.66. These differences proved significant (p < 0.005). Mean speed of movement of spermatozoa before treatment was 1.95m m/s (micrometers per second), after treatment - 3.63m m/s respectively. These differences proved significant (p < 0.001). No changes were established concerning the ejaculated volume. In both cases (prior to and post treatment) the ejaculated volume was within the limits of the norm, about 4 ml on the average. The number of spermatozoa was increased by a mean of 3 millions per 1 ml for the group. In some cases after repeated treatment with a daily dose of six tablets, a normalization of the spermatogram was observed. In those cases, the improvement in the spermogram (normalization of the increased viscosity, increased volume of the ejaculate, increased concentration and accelerated movement of the spermatozoa) was accompanied by increased serum level of luteinizing hormone (LH) and testosterone with decreased estradiol.
Treated patients with idiopathic azoospermia are of certain interest. The results were significant in three, out of 7 patients treated for 90 days with a daily dose - 1.5 g. No spermatozoa were established before treatment. After treatment, spermatozoa concentration per 1 ml of one of the patients was established to be 3.5 millions; in the second - 15 millions and in the third - 28 millions. The percentage of the motile spermatozoa in one of the patients was 10, and in the other two - between 25 and 30. The speed of spermatozoa movement was about 5 micrometers per second. In two of the patients - 30 - 40 spermatozoa in a field were observed and in another patient - about 5, after treatment, versus none - before treatment.

No effect was observed in one of the patients. The studies continue with the administration of a supporting dose to the patients from that nosological entity.

Clinical assessment of the results, obtained after treatment with proviron of patients with idiopathic azoospermia and of the same patients after Tribex treatment, disclose positive results in 3 patients (out of 6 treated), unsuccessfully treated with proviron for long time, and favorably affected by Tribex.

Results among treated males with varicocele and oligoasthenospermia, as regards spermatozoa motility are unidirectional in all research teams, despite differences in the dosage and duration of the treatment. Protich et al. Established 26.88 per cent motile spermatozoa on the average before treatment, and after 60-day treatment with a daily dose of 3 x 1 tablets - 39.06 per cent respectively ( p < 0.02) with a mean speed of spermatozoa movement 2.06 micrometers per second before treatment and 4.44 micrometer per second - after treatment. No changes in the volume of ejaculate and concentration were established. Another research team (Viktorov et al.) established the most pronounced changes in ejaculated volume, after 90-day treatment, with a daily dose of 1.5 g, which grew to 4.5 ml versus 1 - 2 ml before treatment, i.e. an average increase in ejaculate quantity by 1.55 ml in all patients. Number of spermatozoa per 1 ml from oligospermia reached after treatment normospermia in 100 per cent of the patients. The average percentage of motile spermatozoa, for the group before treatment, was 3.05, rising after treatment to 33.09 (Table 1).

Results from Tribex treatment of patients with unilateral or bilateral hypotrophy of the testes and azoospermia deserve attention. The patients complain of a sense of heaviness, sense of swelling and light pain in the region of the testes between the 40th and 60th day after the initiation of the treatment with a daily dose of 6 tablets. At examination, light palpable pain was established in the testicular region, with slight edema, but no further data for pathological changes. By the end of the treatment, improvement both in ejaculated volume and in the concentration was observed as well as in spermatozoa motility. Testosterone serum level was increased from 1.75 mg/ml before treatment to 3.75 mg/ml - after treatment. The palpable pain in the region of the testes abated 2 - 3 months after the treatment.

Tribex administration to patients with chronic inflammatory processes of the prostate and a disturbed spermogram led to negligible changes in the latter in cases, when the inflammatory processes had previously been treated.

No changes were observed among patients with chronic inflammation of the prostate (not previously treated inflammation).

From 14 patients treated, with reduced libido sexualis without particular changes in the sexual organs, obvious improvements was established in the libido of 12 subjects after 30-day treatment (daily dose 3 x 2 tablets, one patient was slightly improved after 60-day treatment and in one patient - no effect was attained. Out of 36 patients treated, with chronic prostatitis and reduced libido, 15 patients were influenced very favorably by the end of the treatment (a total dosage 90 - 100 g), 12 patients - favorably and in 9 of the cases, with a duration of the inflammatory process over 5 years - no effect was obtained. Patients with a hypotrophy of the testes and idiopathic azoospermia had no complaints as regards the libido, but in the process of the treatment, with a view to spermogram improvement, evident enhancement of the libido was established.

Among 9 patients treated, with one of the gravest forms of male hypogonadism (Klinefelter’s syndrome), due to chromosomopathy, with increased number of chromosomes, libido was improved in three, erections occurred in two and in two coitus and masturbations respectively became frequent.



Table 1

1. Results of Tribex treatment (3 x 1 tabl., 60 days) in 38 men, having idiopathic oligo-asthernozoospermia (mean values)


Indices
Before treatment
After treatment

a. Spermatozoal concentration, millions/ml
22.97
26.66

b. Motility %
29.00
35.66*

c. Rate of movement, micron/sec.
1.95
3.76*





2. Results of Tribex treatment (3 x 1 tabl., 60 days) in 16 men after varicocele operation, having also oligo-asthenozoospermia

Indices
Before treatment
After treatment

a. Spermatozoal concentration, millions/ml
21.31
26.75

b. Motility %
11.53
39.06*

c. Rate of movement, micron/sec.
2.00
4.44*





3. Results of Tribex treatment (3 x 2 tabl., 90 days) in 36 men after varicocele operation, having also oligo-asthenozoospermia

Indices
Before treatment
After treatment

a. Spermatozoal concentration, millions/ml
40.60
76.00*

b. Motility %
3.05
33.09*

c. Rate of movement, micron/sec.
2.06
4.44*



In those patients, an increase of LH was established after the treatment - from x = 19.0 to x = 22.0. The rest of the hormones and cholesterol were reduced. FSH from x = 48.19 to x = 42.89; progesterone from x = 2.85 to x = 1.9; testosterone from x = 8.02 to x = 5.0; estradiol from x = 0.061 to x = 0.057 and cholesterol from x = 203.67 to x = 193.67. The treatment of two patients with high sexual gland deficiency (Noonan’s syndrome) led to improvement of the libido and erection in both of them. In one of them self-confidence was improved and in the other one - mossy hairiness in pubic region appeared.

Results from the treatment of three patients with cryptorchidism (one with malformation not corrected), libido was enhanced and masturbations became more frequent. In one subject from that group - aged 37, the duration of erections became longer. In the same patient, one month after treatment, i.e. on the 90th day, the spermogram was decisively improved against the initial level before treatment. In one patient with secondary hypogonadism, light growth of pubic and axilliary hairs was observed parallel to enhanced libido and frequent masturbation under Tribex effect.

In 20 patients of different nosological entities testosterone increased from lower to the upper reference limit; in 7 patients, with serum testosterone level under the low reference limit before the treatment, was increased to the physiological limits; in the rest of the cases with normal values of testosterone before treatment, its level was not considerably changed after treatment.



3.3 TOLERANCE AND SIDE EFFECTS

All clinicians, engaged in these investigations, reported very good tolerance and no side effects. Clinical-laboratory data in Tribex-treated males disclosed no deviations in blood count, ESR, flocculation tests and urine.


3.4 DISCUSSION ON THE RESULTS

Clinical investigations of the three teams, on a total of 212 males with disorders in the sexual function, confirmed experimental data pointing at a pronounced stimulating effect on sexual function by the new Bulgarian phytochemical preparation. Administered in average daily doses of 1.5 g in the course of 30-40 days, it restores and improves libido sexualis in all forms of impotentia coeundi. That suggests that is not only stimulates reduced libido but also has a therapeutic effect on more severe cases as well as in primary and secondary male hypogonadism. Results revealing that the preparation has a favorable effect on spermatozoa motility after 60-day administration, correspond to experimental data, according to which the preparation stimulates both the division and the maturing of the germinative cells.
It is well known that minimums of 80 days are necessary from the division of spermatogonia till the formation of mature spermatozoa in a male. That is the reason for the discrepancies in the results concerning spermatozoa concentration. The team following up a therapeutic course of 90 days found a very good effect both on spermatozoa motility and concentration. Ejaculate samples studies on the 60th day in patients, treated during 60 days showed a marked effect on motility and a negligible effect on concentration, based on identical initial sperm level and the same nosological entity before treatment. This leads to the convincing conclusion that the necessary minimum treatment is one whole germinative cycle concerning spermatogenesis (i.e. 80 - 90 days in man).

Idiopathic oligo- and azoospermia are diseases with a still non-elucidated etiology. In the majority of the cases serum hormonal level is not changed. The effect on patients with such ailment points at a very good therapeutic value of the preparation. Data from biopsies of the testes are pathologically altered and hence - favorably influenced by the preparation.

Koumanov et al. Present a hypothesis of central effect, relating to the mechanism of action of the preparation, based on an increased level of luteinizing hormone (LH). On the other hand, they admit a peripheral effect as well, consideration given to the effect of the preparation on hairiness.

Reduction of serum cholesterol under the influence of the preparation gave grounds to the same authors to presume that it influences cholesterol metabolism. The mechanism of action of the preparation is so far not clear.

It could be concluded, based on clinical studies at present on the new original phytochemical preparation Tribex, that a very good stimulating and therapeutic effect on all forms of impotentia coeundi is present. The preparation disclosed a very good therapeutic effect on oligoasthenospermia. It is distinguished be a very good tolerance and without any side effects. Consideration given to all these facts, we recommend the preparation for the treatment of impotentia coeundi and impotentia generandi, due to oligospermia and reduced spermatozoa motility.



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3. Gyulemetova, R., M. Tomova, M. Simova, P. Pangarova, S. Peeva, A propos of Tribex standardization. Die Pharmazie, 1982, 34,4.

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14. Krueger, P.M., C.D. Hogden, K.I. Sherins. New evidence for the role of the Sertoli cells and spermatogonia in feedback control of FSH-secretion in male rat. Endocrinology, 1974, 95/4. 955-962.

15. Lacy, D. The seminiferous tubule in mammals. Endeavor, 1967, 26, 101-108.

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J. Clin. Endocrinol. Metab., 1969, 29, 467-478.

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21. Tomova, M., R. Gyulemetova. Steroid saponin and Steroidsapogenine VI. Furastanol bisglykosid aus Tribulus terrestris L., Planta medica, 1978, 34, 188-191.

22. Tomova, M., R. Gyulemetova, Sl. Zarkova - license (11) 27584 AGIR 35/1978.

23. Tomova, M., R. Gyulemetova, Sl. Zarkova et al. - license 68428/18.1.1985.

[FUZO]

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[HungarianBeast]

TweetVery good article...gotta get me some tribulus!

[NeverSatisfied]

Tweetyeah good read

[jipped genes]

Tweeti use it after PCT and love it.