TRIBESTAN - Viagra from Balkan

    -  Viagra from Balkan

Tribestan is safe, non-hormonal preparation, which stimulate sexual functions in both Men and Women.

Tribestan was developed and approved for production and use in practice in Europe in 1981. Information about the plant became known in America in 1983 from the self-published Handbook of Chinese Herbs and Formulas, volume 1, by Him-che Yeung in Los Angeles, and the 1985 Chemical Constituents of Oriental Herbs, volume 2, by Hong-Yen Hsu and others (Long Beach: Oriental Healing Arts Institute). Most of the available research, however, has been conducted and published in Europe

 

                                                                                                      

 

                                                          

       1 TRIBESTAN Box  (60 tablets,  250 mg/each) for only        $19.97 

                                                                                                                (click on price to order)

 

 



Dietary supplement which restores and improves libido  sexualis in men, and prolongs the duration of the erection. It  exerts a stimulating influence on spermatogenesis by increasing the number of spermatozoa and their mobility.

· Increased sex drive and higher levels testosterone
· Increased anabolic hormones to optimum level
· Improved sexual function
· Improves libido sexualis in men and women

 



It increases the level of testosterone. It improves libido sexualis in women, exerts a slight stimulating ovulation effect. In has favorable influence on vasomotory manifestation during natural and post-castration climacterium, as well as subjective complains such as insomnia, general tenseness, irritability or apathy, etc

 

Thousands of people are now enjoying increased potency and they owe it all to TRIBESTAN Tablets. They know Tribestan Tablets really works!

Tribestan has been sold in Europe for many years and is how available in America without a prescription.

We know our customers love it! And if you are not using it, you are missing out!

Order today and feel the difference

 

                                                                                                      

 

                                                          

       1 TRIBESTAN Box  (60 tablets,  250 mg/each) for only        $19.97 

                                                                                                                (click on price to order)

 

 

 

 

CHEMICAL PHARMACEUTICAL RESEARCH INSTITUTE

 

SOFIA, BULGARIA

TRIBESTAN ®

 

EXPERIMENTAL AND CLINICAL INVESTIGATIONS

 

CONTENTS

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, Tribestan, 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 IFORMATION ON TRIBESTAN

Tribestan 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), Tribestan stimulates their sexual behavior.

Clinical trials with the preparation confirmed once more experimental data.

Tribestan, 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 Tribestan treatment the libido was enhanced and spermogram improved. In patients with primary and secondary hypogonadism, restored and enhanced libido was observed after Tribestan 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

Tribestan 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 Tribestan 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.

 

Fig 1. Tribestan stimulating effect on spermatogenesis

a) Control b) Experiment

 

1.Spermatogonium 2. Spermatocyte 2. Spermatid 4. Residual body 5. Spermatozoon

 

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 Tribestan, 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 liford 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 Tribestan-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.

 

Fig. 3 Tribestan effect on Leydig and Sertoli cells

 

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 Tribestan. 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 Tribestan 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).

 

Fig. 6 Tribestan effect in animals with disturbed sexual activity

 

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).

 

Fig. 7 Tribestan effect on the concentration of hormones of the hypophyseal-gonadal axis in blood plasma of healthy males

 

 

 

 

 

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.

 

Fig. 8 Tribestan effect on plasma concentration of the hypophyseal-gonadal axis hormones in healthy women

 

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 doze 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. Tribestan 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 STUIDES

 

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 Tribestan 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 Tribestan 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

 

Tribestan 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 Tribestan 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 Tribestan 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 Tribestan- 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 Tribestan 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 Tribestan. 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, Tribestan-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. Tribestan 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 Tribestan 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 Tribestan 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 Tribestan 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 oligoasthenozoospermia - 39 subjects, resection of the left internal testicular vein, due to varicocele with oligoasthenozoospermia - 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 Tribestan. 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 Tribestan-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 Tribestan 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 Tribestan treatment, disclose positive results in 3 patients (out of 6 treated), unsuccessfully treated with proviron for long time, and favorably affected by Tribestan.

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 Tribestan 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.

Tribestan 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 Tribestan 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 Tribestan 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 Tribestan 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 Tribestan 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 Tribestan-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 Tribestan, 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.

 

REFERENCES

 

1. Vankov, S. A propos of Tribestan pharmacology. Scientific-technical Report, 1980

2. Viktorov, Iv., D. Kaloyanov, Al. Lilov, L. Zlatanova, Vl. Kasabov. Clinical investigations on Tribestan in males with disorders in the sexual function MBI, 1982 (in print)

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

4. Gendjiev, Z. Studies on Tribestan carcinogenicity. Scientific-technical Report, 1981.

5. Dikova, N., V. Ognyanova. Pharmacokinetic studies on Tribestan. Anniversary Scientific Session ‘35 Years Chemical Pharmaceutical Research Institute" Sofia, March 22-23, 1983

6. Ilieva, Z. Embryotoxic and teratological studies on Tribestan. Scientific-technical Report, 1981

7. Koumanov, F., E. Bozadjieva, M. Andreeva, E. Platonova, V. Ankov. Clinical trial on Tribestan. Exper. Med., 1982,2.

8. Milanov, S., E. Maleeva, M. Taskov. Tribestan effect on the concentration of some hormones in serum of healthy subjects (Firm documentation).

9. Nikolov, R. Neuropharmacological Study on Tribestan. Scientific-technical Report, 1981

10. Protich, M., D. Tsvetkov, B. Nalbanski, R. Stanislavov, M. Katsarova. Clinical trial on Tribestan on infertile males. Scientific-technical Report, 1981

11. Tanev, G., S. Zarkova. Toxicological studies on Tribestan. Scientific-technical Report, 1981.

12. Tomova, M., R. Gyulemetova, S. Zarkova. An agent for stimulation of sexual function Patent (11) 27584 A61K35/1978.

13. Kerr, J.B., D. M. De Krester. Cyclic variation of Sertoli cell lipid content throughout the spermatogenetic cycle in the rat. J. Reprod. Fertil., 1975, 43/1, 1-8.

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.

16. Leblond, C., P.Y. Clermont. Definition of the states of the cycle of the seminiferous epithelium in the rat. Annals of the New York, Acad., Sci., 1952, 548-573.

17. Mancini, R.E., A.C. Seiguer, A. P. Lioret. Effect of gonadotropins on the recovery of spermatogenesis in hypophysectomized patients.

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

19. Steinberger, E., A. Steinberger, W.H. Perloff. Initiation of spermatogenesis in vitro. Endocrinology, 1964, 74, 788.

20. Steinberger, E. Hormonal control of mammalian spermatogenesis. Physiol. Rev. 1971, 51/1, 1-22.

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.

 

 

 

4. CLINICAL STUDIES IN WOMEN WITH ENDOCRINE INFERTILITY OR MENOPAUSAL SYNDROME

 

P. Tabakova, M. Dimitrov, B. Tashkov

1st Obstetrical and Gynecological Hospital "T. Kirkova" - Sofia, Bulgaria

 

The therapeutic effect of the preparation Tribestan on the endocrine function of women was studiet by the team in the last years. The first clinical trials were carried out on women with dysovulatory syndrome and infertility and later they were redirected to the pre-menopausal and menopausal syndrome. Women with postoperative castration-induced menopause were included in a separate group.

 

4.1 Materials and methods

 

The preparation Tribestan - film-tablets of 250 mg contains a natural product obtained from the superterrestrial part of the plant Tribulus terrestris L. with a predominant content of protodioscine. Control experiments were performed with placebo tablets of the same commercial appearance.

 

4.2 Regimens of application

 

Group A - women with dysovulatory disorders and infertility

1. Regimen recommended by the producer: 1 - 2 tablets 3 times a day for a period of 2 to 3 months.

2. Our regimen: 3 x 1 tablets up to 3 x 2 tablets daily from the 5th up to the 14th day of the menstruation cycle for a total period of 2 - 3 months.

3. After follow-up of a set of parameters to evaluate the integral effect of Tribestan only the regimen is switched over to combined therapy with Tribestan + hormonal preparation to stimulate ovulation:

a) Tribestan according to regimen 2 + Stimovul (Organon) 1 - 2 tablets from the 5th up to the 14th day of the cycle for 3 months.

b) Tribestan according to regimen 2 + Clostylbegit (Hungary) 1 - 2 tablets daily from the 5th up to the 9th day of the cycle for 3 months.

 

Group B - women with the menopausal syndrome

1. Tribestan - 3 x 2 tablets for 20 days and tapering the dosage by one tablet every 4 - 5 days to come down to the maintenance dose of 2 x 1 tablet a day for a total period of time strictly individualized depending on the degree of the effect obtained.

2. Tribestan - 2 x 2 tablets for 30 days with subsequent reduction in the dosage every 4 - 5 days to 2 x 1 tablet daily

3. Tribestan - 3 x 1 tablet continuously and for a long period of time (up to 1 year).

 

4.3 Clinical contingent

 

Group A - 51 women with diagnosed primary and secondary endocrine infertility treated in the 1st Obstetrical and Gynecological Hospital "T. Kirkova", Sofia in the period 1983 - 1984. Fifteen of them were treated by regimen 1 and remaining 36 - by regimen 2 and after the 3-month period of observation the combined therapy by regimen 3 was used on 20 of them. Parallel control studies on a comparable contingent were carried out with hormone preparations: Stimovul (Organon) - 62 women; Clostylbegit (Hungary) - 21 women; Fertodur (Schering) - 29 women. The total number of women covered by the study was 163.

 

Group B - 50 women with diagnosed natural or post-castration menopausal syndrome treated in the period 1986 - 1987. A pilot study with further 12 women was carried out as early as in 1984. In 46 of 50 women (92%) immediately after verifying the diagnosis and the degree of manifestation of the clinical picture of menopause we initiated treatment with placebo 3 x 2 tablets a day for a total period of 15 - 20 - 30 days. Having registered the effect of placebo tablets we continued with Tribestan therapy using above regimens.

 

4.4 Parameters of observation and recording

 

For the clinical contingent of Group A

 

The final result from the treatment was classified in 3 types: Normalization of ovulation with subsequent pregnancy; normalized ovulation without pregnancy; no effect. The following parameters were recorded: subjective sensations (changes) in general condition and libido sexualis; onset and duration of menstruation; basal temperature; hormonal vaginal cytopreparations; pregnandiol, 17-OH-KC in the urine histological changes in the endometrium; echographic folliculometry; radioimmunological control of gonadotropic and steroid production; hysterosalpingographs and laporoscopy to determine the state of the fallopian tubes and their elimination, as far as possible, as causes of infertility.

 

For the clinical contingent of Group B

 

The results of treatment were classified depending on the clinical picture as complete disappearance of menopausal complaints; great decrease of the former; no effect on complaints. The following parameters in the nervous vegetative and neuro-psychic complaints intensity and frequency of the hot flash and sweating, depression or superexcitation, easy fatigability, apathy, etc.; changes in cardiovascular system - changes in the pulse and blood pressure, oppression in the heart region, tachycardia or extasystoles, etc.; micturition disorders, pruritis in the external genitalia; hormonal cytopreparations; blood count and blood sugar profile; ultrasonic diagnostics; radioimmunological control of gonadotropic and steroid hormones and changes in libido sexualis.

 

4.5 Results and discussion

 

Group A

 

Fifteen patients were treated by regimen 1. None of them showed any essential changes in parameters determining the occurrence of ovulation. Moreover, there were noted some undesirable effects such as a longer menstruation cycle, excessive libido sexualis and related general excitability and insomnia, and in case of abrupt discontinuation of the drug intake at the end of the 3rd month or in the event of reducing the dose by 50% only - a drastic decrease of libido sexualis and general weakness. It made necessary to apply regimen 2 to the remaining 36 patients - the data are down in the following figures and tables. The distribution of women treated with Tribestan is given in Fig. 1. The prevailing number of them were in the age group 20 - 30 years old and only 2 were over 36 years of age. Nineteen patients that were with primary hormonal infertility and 18 - with secondary hormonal infertility, i.e. the number was almost equal Fig. 2. The distribution of patients with regard to previous treatment is shown on Fig. 3. One can note that those untreated previously were about 36% of the women; others with prior hormonal or surgical correction of ovaries were almost the same number - 20 - 30% and the smallest was the group with combined hormonal + surgical therapy. In Table 1 we show lower values of unsatisfactory treatment with Tribestan (33.3%) compared to Clostylbegit (52.4%) or Fertodur (76%). Undoubtedly best results were obtained with Stimovul - normalized ovulation with subsequent pregnancy - 39%; normalized ovulation without resultant pregnancy - 35.5% and no effect 26%. On the background of this picture Tribestan has considerably more moderate effect: 24 of the total number of 36 treated women had normalized ovulation but only in 2 of them where followed pregnancy and in 12 patients it had no basic effect. Twenty women were treated simultaneously with Tribestan and an ovulation stimulant. The effect from their combined use was better compared to treatment with single agents. Probably here there is a complex effect - hormonal stimulation of ovulation is combined with increased libido sexualis and improved general and psycho-emotional condition of the infertile couple particularly taking into account the fact that we recommended the use of Tribestan also to husbands. No side effects were observed in the intermittent application of Tribestan.

 

 

 

COMPARATIVE DATA ON THE EFFECT OF TRIBESTAN

STIMOVUL, CLOSTYLBEGIT, FERTODUR ON FEMALES

WITH ENDOGENOUS INFERTILITY

Table 1

 

Groups by method of treatment

Number

Therapeutic results

   

Normalized ovulation with pregnancy

Normalized ovulation, no pregnancy

No effect

Side effects

Treated with Tribestan

36

2 ( 5.6%) 22 (61.1%) 12 (33.3%) None
Treated with Stimovul

62

24 (38.7%) 22 (35.5%) 16 (85.8%) 4 ( 6.5 %)
Treated with Clostylbegit

21

4 (19.0%) 6 (28.6%) 11 (52.4%) 8 (38.1%)
Treated with Fertodur

29

2 ( 6.9%) 5 (17.2%) 22 (75.9%) 3 (10.6%)
Total

148

32 55 61 15

Group B

 

The age distribution of the patients in this group is represented in Table 1. Only four of them are younger that 40 years and 2 - over 60 years of age. Eighty percent of all treated women are in the age group 40 - 55.

Twenty-six patients were with natural onset of the menopause and the remaining 24 (48%) - postoperative castration climacteric (Table 2). The duration of the menopausal syndrome is shown in Table 3. As seen in a considerable part of the menopause dated back one year prior to therapy with Tribestan. Those were mainly women with postoperative menopause.

 

EFFECT ON TRIBESTAN DURING MENOPAUSE

DISTRIBUTION OF PATIENTS BY AGE

Table 1

 

Age group (years)

Number of patients

Percent

30 - 34

1

2.0

35 - 39

3

6.0

40 - 44

8

16.0

45 - 49

19

38.0

50 - 54

13

26.0

55 - 59

4

8.0

60

2

4.0

Total

50

100.0

EFFECT OF TRIBESTAN DURING MENOPAUSE

DISTRIBUTION OF PATIENTS

BY TYPE OF MENOPAUSE

Table 2

Type of Menopause

Number of patients

Percent

Natural

26

52.0

Postoperative

24

48.0

Total

50

100.0

EFFECT OF TRIBESTAN DURING MENOPAUSE

DISTRIBUTION OF PATIENTS

BY DURATION OF MENOPAUSE

Table 3

Duration of Menopause (months)

Number of patients

Percent

< 12

19

38.0

12 - 35

16

32.0

36 - 50

7

14.0

> 60

8

16.0

Total

50

100.0

The clinical picture of the menopausal syndrome in the group under study was predominant by several major symptoms represented diagrammatically on Tables 4 and 5.

 

EFFECT OF TRIBESTANDURING MENOPAUSE

DISTRIBUTION OF PATIENTS BY INCIDENCE

OF SOME SYMPTOMS BEFORE TRIBESTAN

Table 4

Symptoms

Number of patients

Percent

Heat waves

50

100

Perspiration

39

78

Depression

27

54

Hyperexitation

22

44

Sleeplessness

41

82

Tenseness

18

36

Heaviness in the heart region

30

60

RR - changes

11

22

ECG - changes

8

16

EFFECT OF TRIBESTANDURING MENOPAUSE

DISTRIBUTION OF PATIENTS

BY TYPE OF LIBIDO SEXUALIS

Table 5

Type of libodo sexualis

Number of patients

Percent

Normal

2

4.0

Low

20

40.0

Very low

28

56.0

Total

50

100.0

Nervous vegetative manifestations were quite frequent with all treated women. The hot flash was present in 100% of the women, sweating - in 78%; insomnia - 41 patients (82%); unmotivated superexcitation - 44%.

From the cardiovascular changes the oppression in the hearth region was predominant (60%) and changes in the blood pressure and ECG were observed in 16 women (22%). Libido sexualis was unchanged in only two women (in comparison with the previous state). Greatly decreased to completely lost desire for sexual contacts were characteristic to 56% of all patients. It should be underlined that the intake of placebo tablets by 46 from 50 women did not result in a favorable effect on any complaint (Table 6).

 

EFFECT OF TRIBESTAN DURING MENOPAUSE

DISTRIBUTION OF PATIENTS

BY DURATION OF PLACEBO TREATMENT

Table 6

Duration of treatment (days)

Number of patients

Percent

0

4

8.0

14

6

12.0

15 - 20

32

64.0

21 - 30

8

16.0

Total

50

100.0

According to the selected signs for classification we established complete or almost complete disappearance of all or most of the symptoms in 49 from 50 treated patients (98%). Only in a woman Tribestan had no effect on the menopausal syndrome and she was transferred to other treatments. Table 7 shows that 50% of the treated women the course of treatment needed no less than 110 up to 180 tablets to achieve a favorable effect. In 10% of the women this dose was even higher - 190 - 200 tablets. The average doses are given in Table 8 and in the greater number of women those were more than 100 tablets per course of treatment. The effect obtained was retained by a maintenance dose of 2 - 3 tablets a day in 84% of the treated women (Table 9).

 

EFFECT OF TRIBESTAN DURING MENOPAUSE

DISTRIBUTION BY PATIENTS BY THE TOTAL

EFFECTIVE DOSE OF TRIBESTAN

Table 7

Initial dose (tablets/day)

Number of

Tablets

3 x 1

2 x 2

3 x 2

Total

No

%

No

%

No

%

No

%

< 60

2

4

-

-

-

-

2

4

60 - 100

5

10

5

10

8

16

18

36

110 - 180

-

-

7

14

18

36

25

50

190 - 220

-

-

1

2

1

2

2

4

> 220

-

-

-

-

3

6

3

6

Total

7

14

13

26

30

60

50

100

EFFECT OF TRIBESTANDURING MENOPAUSE

TOTAL EFFECTIVE DOSE OF TRIBESTAN

Table 8

    Total Effective Dose
Dose

(tabl./day)

No

Mean

Limit of confidence

(mean ± 1.96 SEM)

3 x 1

7

68.6

53.0 ÷ 84.2

2 x 2

13

115.4

93.7 ÷ 137.1

3 x 2

30

141.5

113.7 ÷ 169.3

EFFECT OF TRIBESTANDURING MENOPAUSE

DISTRIBUTION OF PATIENTS BY THE SUPPORTING

DOSE OF TRIBESTAN

Table 9

Supporting dose

(tabl./day)

Number of patients

Percent

2 x 1

27

55.1

3 x 1

14

28.6

2 x 2

8

16.3

Total

49*

100.0

* 1 patient without effect

The dynamic cytological monitoring of the progesterone - estrogen level (vaginal cytopreparations) showed that only in 14% of the patients there was present a high initial level of estrogens, while in 44% of them it was low or very low (Table 10).

 

EFFECT OF TRIBESTAN DURING MENOPAUSE

DISTRIBUTION OF PATIENTS BY LEVEL

OF PREGESTERON/ESTROGEN ACCORDING TO HORMONAL

CYTOLOGICAL EXAMINATION

Table 10

Level

Number of patients

Percent

High

7

14

Normal

1

2

Low

6

12

Very Low

16

32

Total

30*

100

* 20 patients without cytological examination

The particular strict radioimmunological monitoring is shown on Table 11 and Table 12

 

EFFECT OF TRIBESTAN DURING MENOPAUSE

RADIOIMMUNOASSAYS

Table 11

Hormone Tribestan treatment

No

Limit of confidence

(mean ± 1.96 SEM)

FSH Before

After

46

42

51.38 ÷ 72.34

42.30 ÷ 59.74

LH Before

After

42

43

32.45 ÷ 46.05

29.62 ÷ 38.38

Prl Before

After

42

37

265.20 ÷ 378.20

200.60 ÷ 267.60

EFFECT OF TRIBESTAN DURING MENOPAUSE

RADIOIMMUNOASSYS

Table 12

Hormone Tribestan treatment

No

Limit of confidence

(mean ± 1.96 SEM)

E2 Before

After

42

40

0.10 ÷ 0.22

0.20 ÷ 0.54

Prg Before

After

32

34

5.00 ÷ 10.30

4.14 ÷ 7.44

Tst Before

After

41

45

1.15 ÷ 1.74

0.96 ÷ 1.30

The variance analysis showed that both mean values and the confidence interval are within the limits normal to the age. Comparison of these data prior to and after therapy showed that gonadotropic hormones had a tendency to decrease compared to the initial values, while the ovarian hormones did not demonstrate such a tendency even there was insignificant increase especially in E2. These data together with the clinical picture can account for the favorable influence on the menopausal complaints and the considerably enhanced libido sexualis in 2/3 of the treated women.

In this case the effect of Tribestan is equivalent and in some cases even better than that of the estrogen-testosterone hormonal preparation Ambosex without the adverse side effect of the latter such as virilization and tendency of weight gains.

 

4.6 Side effects in treatment with Tribestan (nausea, vomiting, allergic phenomena, intolerance, etc.) were not observed. The preparation is well tolerated. It is worth while the fact that after achieving the desirable effect the abrupt decrease in the effective dose down to the maintenance dosage results in the sudden and complete unlocking of almost the whole menopausal symptom complex. Therefore, the transition from the effective dose to the maintenance dose should be gradual and for a longer period of time.

 

5. CONCLUSION

 

Our long-term experience with the use of the preparation Tribestan for treatment of infertility mainly in women but quite frequently in men as well, make us recommend it in case of disturbed gamete formation due to stress situations, long years of infertile marital life, impaired or almost missing libido sexualis, etc. Leading to anovulatory menstruation cycles, dyskinetic changes of fallopian tubes and qualitative changes in the sperm of man.

Combination of Tribestan with suitable hormone preparations results in potentiating its positive effect, which explains its use in everyday practice for treatment of infertility in the family.

The opinion of the research team based on the experience from treatment in the last years of more than 150 women with natural or postoperative menopause is that Tribestan can successfully be used for treatment of the menopausal syndrome in women.

 

TRIBESTAN®

Composition:

A natural product obtained from the over-the-ground part of the plant Tribulus terrestris L., containing mainly steroid saponins of the furostanol type with a predominant quantity of protodioscin (not less than 45%).

 

Synonyms:

None

 

  

Action:

Non-hormonal preparation, which restores and improves libido sexualis in men, improves and prolongs the duration of erection. It exerts a stimulating influence on spermatogenesis by increasing the number of spermatozoa and their motility. It increases the level of testosterone.

 

It improves libido sexualis in women, exerts a stimulating ovulation effect, it has a favorable influence on vasomotor manifestation during natural or post-castration climacteriums, as well as on subjective complains such as insomnia, tenseness, irritability or apathy, etc.

 

Indications:

In men: - impotentic coeundi in Kleinfelter’s syndrome, varicocele, cryptorchism, hypotrophy, syndrome of Noonan, sterility on the basis of idiopathic oligoasthenozoospermia, idiopatic azoospermia, varicocele, hypotrophy of testicles.

In women - endocrine ovarian sterility, climacteric and post-castration syndrome with expressed vasomotory and neurashenic manifestations.

 

Contradictions:

None

 

Application and dosage:

In men - the dosage and duration of treatment are determined according to the character and gravity of disease. Most often, the dose is 1 - 2 tablets 3 times a day during meals. The treatment duration is as follows: in case of impotentio coeundi - 40 - 50 days at least. In sterility - 70 - 90 days.

 

In women the treatment is strictly individual and depends on the gravity of manifestations. The dose most often used here is also 1 - 2 tablets 3 times a day during meals. In cases of sterility the preparation is applied from the 1st to the 12th days of the menstrual cycle. In post-castration and climacteric syndrome the treatment lasts 60 - 90 days. After an improvement is obtained the dose is reduced to 2 tablets daily for another 50 - 60 days as supporting dose.

 

Side effects:

None

 

Pharmaceutical form and packaging:

Box containing 60 film-tablets of 0.250 g.

 

Storage:

In a dry and dark place.

 

                                                                                                      

 

                                                          

       1 TRIBESTAN Box  (60 tablets,  250 mg/each) for only        $19.97 

                                                                                                                  (click on price to order)

 

 

1