chazk said:
"Users can easily expect to put on 5-10 pounds within 4 weeks, and continued gains thereafter. The gains experienced on AndroGenerator are dry and hard, as the user will not experience any water-retention at all."
5-10 lbs of soild lean muscle tissue no water retention is a big claim to make in with in 4 weeks time.
I could careless about people's logs, online journals. Do you have double blind placebo studies to back your claims ?
Users will gain that weight from the CEEM alone!
Nonetheless, check out these studies on the other ingredients!
THE ANABOLIC EFFECTS OF LJ100™
For a printable copy of this study, please click here.
Sareena Hanim Hamzah & Ashril Yusof
Department of Exercise Physiology, Sports Centre, University of Malaya, Kuala Lumpur
Introduction
Eurycoma longifolia (LJ100™) is a tall shrub tree of a Simaroubaceace family and is commonly found along the hilly jungle slopes of Malaysia. It has been used for years as a traditional medicine to treat fever, ulcer, malarial, swelling, reduce high blood pressure and fatigue. However, LJ100 is better known for its aphrodisiac properties. In a clinical study by Ismail (2002), he demonstrated that this herb enhanced sexual activities and increased free testosterone levels in men. Increases in testosterone levels is associated with an improvement in fat free mass, muscle size and muscle strength in men (Brodsky, 1996; Bhasin, 1997), which could be further amplified by strength training (Bhasin, 1996). In this study, the effect of LJ100 water-soluble extract on body composition and muscle size in men will be measured.
Methods
Fourteen healthy adult males (age 25.64 ? 3.73 years) received either 100 mg/day LJ100 water-soluble extract (n = 7) or placebo (n = 7) for 8 weeks. Simultaneously, both groups performed an intensive strength-training program with initial load of 60% repetition maximum (RM), which was carried out on alternate days. A total of 10 exercises, which make up the circuit, were catered towards providing a total lower body and upper body workout. Each workout was done in two sets of 10 repetitions with 1-minute rest in between. The loads were gradually increased 10% per week. Body composition measurement using skin fold test was taken at two sites as recommended by McArdle (1993). A standard strength test that comprised of 1 RM test was administered on the subject to determine their strength. The upper limb strength was measured by determining their ability to resist maximum load using the shoulder press machine (Nautilus, USA) following the American College of Sports Medicine (ACSM, 2001) standard measurement procedure. The arm circumference measurement was taken using a measuring tape at proximal 1/3rd of the arm. Electromyography reading of the isometric contraction of bicep muscle was taken using the surface electrodes. Subjects were instructed to perform an isokinetic flexion of the elbow using free barbells with load of 10 kg for the durations of 5 seconds. The mean amplitude was analyzed using the MyoResearch Software (Noraxon, USA).
All the measurements were taken 1 day prior to supplementation (LJ100 and placebo) and training period, and 1 day after the completion of 8 weeks experiment. All data were analyzed using the Statistical Package for Social Science (SPSS) computer software version 10.0 (2000) for t-test, means and standard deviation. Statistical significance was established at p<0.05.
Results
The results for fat free mass, fat mass, 1 RM, arm circumference, and sEMG of both groups are shown in Table 1.
Table 1. Average fat free mass, fat mass, 1 RM test, arm circumference and sEMG of the group consuming LJ100 water soluble extract and placebo before and after the period of supplementation and training program
* Results of mean ± SD for pre and post experiment showed significant difference (p<0.05)
The fat free mass of the group supplemented with LJ100 water-soluble extract showed a significant increment of approximately 2.1 kg. There were no significant changes in fat free mass in placebo. Body fat percentages were significantly decreased in treatment and placebo. However, a greater decrement was shown in treatment compared to placebo i.e. 9.14% and 6.57%, respectively. The 1 RM test muscle strength test showed an increase in gross muscle power in both groups. The treatment group showed a greater increment in strength compared to placebo i.e. 6.78% and 2.77%, respectively. The mean arm circumference in treatment group increased significantly by 1.8 cm following the supplementation while no significant changes observed in placebo group. The mean sEMG reading of the treatment and placebo showed a significant decrement in values after going through the exercise program. However, the treatment group showed 2.92% higher reduction in electrical activity of the muscle measured at the end of the experiment period compared to placebo (25.70% and 22.78%, respectively). During and after the administration of LJ100, no adverse effects were noted within the treatment group.
Discussion/ Conclusion
In this study, although the testosterone level was not measured during the test period, an increased in fat free mass in treatment group may be linked to the rise in steroidal hormones in the body. The percentage of body fat appeared to decrease in both groups, this finding is in agreement with a study by Brodsky (1996). However, the further decrease in fat mass by the treatment group could be explained by the higher metabolic rate after consuming LJ100. The increment in muscle strength with strength training in both the treatment and placebo groups were consistent with the finding by Kraemer (1993), he suggested that the improvement in strength was caused by the increase in testosterone levels. Jones and Round (1996) proposed that increases in strength are greater than increases in muscle size during the first 6-8 weeks of strength training. Thus, an increase in arm circumference observed in treatment group could be explained by the testosterone enhancing effect of the extract. In conclusion, results obtained from this pilot study suggest that the administration of LJ100 improved fat free mass, reduce fat mass, increase muscle strength and size suggesting LJ100 might be used as an ergogenic aid. Further studies will be carried out to determine the mechanism of action at hormonal and molecular level.
Water-soluble extract of LJ100™ as a potential
natural energizer for healthy aging in men.
M.I.M.TAMBI1, S. OTHMAN2and J.M SAAD2
1Specialist Reproductive Research Center, National Population & Family Development Board, Ministry of Women & Family Development, Malaysia.
2Department of Biochemistry, Faculty of Medicine, University of Malaya, Malaysia.
Introduction
Malaysia has a rich source of rainforests that contain thousands of plants with potential medicinal values. One such plant is the tall shrub tree from the Simaroubaceace family, Eurycoma Longifolia (LJ100™ Tongkat Ali) which is commonly found along the hilly jungle slopes of Malaysia (Burkill and Hanif, 1930). The local name of the shrub is 'Tongkat Ali' or Ali's Walking Stick' which is rather suggestive of its traditional function of sexual support for aging males. Similar trees are also found in other Asian Rainforests; however, it is traditionally known that only two species of the shrub namely E.Longifolia and E.apiculata have medicinal properties (Burkill and Hanif, 1930). The medicinal elements are only found within the roots. The root of Eurycoma Longifolia was used as a decoction by the natives of old Malaya, especially the elderly for strength and energy (Burkill and Hanif,1930), this practice remains to this day.
Early experimental studies on animals were mainly focused on the aphrodisiac properties of LJ100. Mice treated LJ100 demonstrated higher frequency of mounting compared to the control group (Ali and Saad, 1993). Additionally, the serum testosterone of the dissected mice showed an increase of 480% compared to the placebo-controlled group (Ali and Saad, 1993). Further studies provided evidence that LJ100 produced a dose-dependent increase in mounting frequency in male rats, hence, acting as a potent stimulator of sexual arousal in the absence of feedback from genital sensation (Ang and Sim,1997). It was also shown that LJ100enhanced and maintained a high level of crossovers, mountings, intromissions, and ejaculations.
Other studies showed that when the extract of LJ100 was injected into male mice, they showed intense physical activities and copulatory behavior (Ang and Sim, 1998). Even frail mice were observed to be active and alert. In another study, LJ100 was exposed to penile muscular tissue of male mice; results demonstrated that the muscular tissue was found to relax. Analysis on the mitochondria homogenates of the liver and penile muscle of the mice showed that the extract could enhance the respiration of mitochondria, leading to 60% increase in ATP production through oxidative phosphorylation (Khamis and Saad, 1993).
Early clinical trials studied the effect of LJ100 on testicular tissues. The samples were incubated along with human testicular tissues taken from men who were orchidectomised as part of treatment of prostate cancer (Aminuddin et al, 1995). There was significant increase in the concentration of testosterone and its precursors. The results suggest that the LJ100 has the ability to increase the biosynthesis of androgens (Aminuddin et al, 1995).
Androgen is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of masculine characteristics in vertebrates. This includes the activity of the accessory male sex organs and development of male secondary sex characteristics. The primary, and most well known, androgen is testosterone.
In this study, we intend to investigate the effect of the LJ100 water-soluble extract on testosterone, dehydroepiandrosterone (DHEA) and sex hormone binding globulin (SHBG) levels in human subjects. Dehydroepiandrosterone (DHEA) is a natural steroid hormone produced from cholesterol by the adrenal glands. Dehydroepiandrosterone is structurally similar to testosterone and estrone and can be easily converted into those hormones (DHEA is a precursor for testosterone). Sex hormone binding globulins are carrier proteins that regulate the amount of unbound steroid in the blood. A decrease in SHBG is associated with an improvement in free testosterone index. Additional parameters that will be measured include Quality Of Life (QOL) via the PADAM score and Sexual Health Inventory Questionnaires (SHI-Q).
Methodology
In a Reproductive Research Center in Kuala Lumpur, Malaysia, 30 human volunteers were recruited in a randomized open trial. The volunteers were selected among married men whose age ranges between 31-52 years. There were no other specific criteria for the selection of volunteers. Dr. Johari M. Saad and co-workers from the Department of Biochemistry, University Malaya, Malaysia, produced LJ100 water-soluble extract of E.Longifolia root.
Upon registration, the volunteers were asked to fill out two questionnaires: (i) a validated Sexual Health Inventory Questionnaires (SHI-Q) and (ii) the PADAM Score Questionnaires. Peripheral venous blood sample was collected from each individual to evaluate his total testosterone hormone, dehydroepiandrosterone sulphate (DHEA) and sex hormone binding globulin (SHBG) levels. Following this, each volunteer was given a supply of the encapsulated LJ100. These were to be consumed regularly for three consecutive weeks, twice daily, and two capsules per day (100 mg/day). The volunteers were requested to come back for a follow-up after week one and week three. During the follow-up sessions, they were asked to again fill out two sets of questionnaires and provide blood samples for analysis of serum testosterone, SHBG and DHEA.
Results
Questionnaires Analysis
Analysis of the SHI-Questionnaire results have shown that 62% of the cases had either increased or a maximum score after consuming LJ100. Another 24% showed reduction while 14% of the cases showed no change in the score (Figure 1). This indicates that the majority of the volunteers demonstrated an increase in their sexual health satisfaction and performance. Breakdown of the SHI-Questionnaire showed subjects has an increase in sexual desire and the success at the attempts at sexual intercourse.
Figure 1: Effect of LJ100™ consumption on SHI-Q Score
PADAM Analysis
Analysis of the PADAM Score demonstrated that 82% of the cases showed a decrease in total score (decrease is positive effect). There is 91% improvement in the sexual PADAM score component, a 73% improvement in the physical component, and an 82% improvement of psychological component. The vasomotor score showed improvement in 50% of the subjects (Figure 2). The improvements in the first three components of the PADAM score reflects that consumption of LJ100 had resulted in an improvement of their quality of life with regards to their physical, sexual and psychological well being.
Figure 2: Percentage of Improvement or Reduction for Various Components of the PADAM Score
Serum Hormones analysis
Testosterone
Total testosterone levels were not significantly different between those raised (43%) and those declined (39%) in this study (Table 1). This gives an initial impression that LJ100 does not have any effect on steroidogenesis. Considering that almost all the volunteers have normal levels of total testosterone, the feedback system is activated to ensure the testosterone levels are within the individual needs range. In 6 volunteers whose serum total testosterone is low, there is an increase in total testosterone on first and third week as well as improvement in the Quality of Life Scores (SHI-Q and PADAM Score).
DHEA
Analysis of the DHEA showed gradual increase from 26% after 1 week to 47% after 3 weeks. This suggests that LJ100may influence the DHEA production, which subsequently would be aromatized to testosterone (Figure 3).
Figure 3: Percentage of Increment in DHEA level
SHBG Analysis
The results showed that SHBG levels were reduced in 36% of the cases after one week and improved to 66% after 3 weeks. This suggests that LJ100 could have an effect on the production of SHBG (Table 2).
Free Testosterone Index Analysis (FTI)
When the SHBG level declines, the Free Testosterone Index (FTI is calculated as a percentage of the total testosterone against SHBG) goes up. Results demonstrated that the FTI increased in 39% of the subjects after 1 week to 73% after 3 weeks (Table 3)
Conclusion
Increasing testosterone is the key factor in increasing sex drive. Testosterone is the most important of the male sex hormones, known as androgens, produced in the gonads. Testosterone plays a key role in the development and maturity of male sex organs. The hormone promotes secondary sex characteristics, including the appearance of facial hair, sexual desire, and sexual behavior. However, testosterone is not just a sex booster for men. Women also produce testosterone, about 5 to 10 percent the amount produced in men. In woman, this vital hormone also stimulates sex drive and produces heightened sensitivity of erogenous zones.
In this study, the aqueous LJ100 extract has a strong potential in providing sufficient free testosterone to the body as demonstrated by the increase in the free testosterone index between weeks one and three. The high score in the Physical and Sexual Domain of PADAM and the Desire and Sexual Attempts in the SHI-Q score suggests this extract can delivery sexual health effects for both men and women.
The results demonstrated that the circulating androgen concentration affects SHBG synthesis. The increase in DHEA levels (DHEA is a precursor to testosterone) between week 1 and week 3 resulted in elevated testosterone levels that caused a decrease in SHBG levels. It is important to note the any decrease in SHBG levels has an overall effect to increase free testosterone index as indicated in table 3. The results of this study suggest that LJ100 inhibits SHBG allowing more free testosterone to remain in the blood. This additional testosterone stems the aging process, improves energy and sexual function, and helps reduce body fat and reduces the risk factors associated with heart health.
Since this study is just an exploratory study to look into the marketing potential of LJ100, the volunteers were asked about personal feedbacks with regard to the extract. The following responses were received:
48% felt that they are feeling healthy, not easily tired, feeling active and energized.
40% felt easily aroused, increase sexual desire and maintained an erection longer.
16% felt their joints and backache are feeling better.
24% felt warm and easily sweat (sign of better circulation)
8% experience better sleep.
8% felt an improvement in their memory.
20% felt their appetite has improved and their bowel movements are better than before.
References
1.Burkill, IH and Hanif, M; (1930) Malay Village Medicine, The Garden Bulletin Strait Settlements.
2.Ali, JM and Saad, JM (1993); Biochemical effect of Eurycoma Longifolia Jack on the sexual behavior, fertility, sex hormone and glycolysis. Dissertation Paper for Bachelor of Science, Department of Biochemistry, University of Malaya
3.Ang, HH and Sim,MK (1997); Effect of Eurycoma Longifolia Jack on sexual behavior of male rats. Archives of Pharmacal Research (Seoul),20(5),656-58
4.Ang, HH and Sim,MK (1998)[1]; Eurycoma Longifolia Jack and orientation in sexually experiences male rats. Biol and Pharmaceutical Bulletin 21(2);153-55
5.Ang, HH and Sim,MK (1998)[2]; Eurycoma Longifolia Jack increases sexual motivation in sexually naive male rats. Archives of Pharmacal Research (Seoul),21(6),778-81
6.Khamis, ZM and Saad, JM (1993); Dissertation Paper for Bachelor of Science, Department of Biochemistry, University of Malaya.
7.Aminuddin, N; Saad, JM; Hadi, AH and Abdullah, R (1995); The effect of Eurycoma Longifolia extracts on androgen synthesis.
LJ100™ Saliva Testosterone Test
Saliva Testosterone Test of 9 Individuals 26-52 years of age
Dosage 2x2 (50mg/capsules) morning & evening for 10 days
Normal range for athlete 800 = 150ng/dl of blood
Volunteers 1-5 are athletes - data are an average of 3 different studies at different times
Volunteers 6-9 do not exercise on a regular basis
Conclusion
The results demonstrate that 100 mg per day of LJ100 caused an increase in bioavailability testosterone within 10 days. Furthermore, all subjects (athletes and non-athletes) showed a positive increase in testosterone suggesting that LJ100 causes an increase in the free testosterone index.
Effect of LJ100 Tongkat Ali on Anabolic Balance During Endurance Exercise
Talbott S, Talbott J, Negrete J, Jones M, Nichols M, and Roza J. Effect of Eurycoma longifolia Extract on Anabolic Balance During Endurance Exercise. SupplementWatch, Inc. Draper, UT, 84020 USA and Source One Global Partners, Chicago, IL 60611 USA.
[email protected]
Eurycoma longifolia, commonly known as “Tongkat Ali” or “Longjack,” is often touted as a testosterone “booster” and marketed to athletes as a training aid and performance enhancer. Rodent studies have shown oral delivery of Eurycoma extract to improve sexual performance and increase serum testosterone levels. Open-label human trials have suggested that Eurycoma extract may help prevent age-associated androgen deficiency, improve sexual function, and increase psychological parameters such as mood, energy, and sense of well-being. The purpose of this study was to determine the effects of Eurycoma longifolia on testosterone and cortisol levels during intense endurance exercise. We used a water-soluble extract of Eurycoma longifolia (E) standardized to 22% eurypeptides and 40% glycosaponins. Male subjects (N=30) were recruited from a 24-hour mountain biking event and asked to provide a saliva sample before and after each lap for measurement of cortisol and testosterone by enzyme immunoassay (Salimetrics, State College, PA). Subjects completed 4 laps (14.91 miles/lap) and provided 8 saliva samples over a 24h period. Subjects consumed 100mg of E or a look-alike placebo (P) approximately 30 minutes prior to endurance exercise. Cortisol levels were 32.3% lower in E compared to P (0.552+0.665 versus 0.816+0.775 ug/dL, P < 0.05). Testosterone levels were 16.4% higher in E compared to P (86.72+40.90 versus 72.47+33.77 pg/mL, P < 0.05). These results suggest that Eurycoma longifolia extract may help to maintain normal levels of cortisol (low) and testosterone (high) and thus promote an overall “anabolic” hormonal state (versus a “catabolic” state characterized by elevated cortisol and suppressed testosterone) during intense endurance exercise.
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TRIBESTAN EFFECT ON THE CONCENTRATION OF SOME HORMONES IN THE SERUM OF HEALTHY SUBJECTS
S. Milanov, A. Maleeva, M. Taskov
RIRR - Radioisotope and Radioimmunological Laboratory, Sofia
Chemical Pharmaceutical Research Institute,
Sofia, Bulgaria
SUMMARY
Tribestan effect has been studied on the serum concentration of hypophyseal hormones, of ACTH, STH, LH, FSH, adrenal hormone aldosterone and cortisol and sex hormones - testosterone and estradiol. The experiments have been carried out on 8 males and 8 females, aged 28 - 45 years of age. The product was perorally administered in a single dose of 250 mg, three times daily for 5 days. Serum samples were withdrawn at 8 a.m. and 12 a.m., prior to and post treatment. The product has been established not to change essentially the concentrations of adrenal hormones and of ACTH. The hypophyseal-gonadal axis however has significantly been affected in the females with predominantly increased concentration of FSH and estradiol and in the males - mainly of LH and the testosterone. The mechanism of that action is presumed to be complicated and realized both by direct effect on gonadal apparatus and by the tropic hormones.
The probable established changes in the concentration of the hormones studied do not get out of the frames of the physiological limits.
The lyophilized extract of Tribulus terrestris, introduced in veterinary practice as TB-68, has pronounced sex-stimulating function. The initial studies of this product showed that it stimulates the spermatogenesis of albino rats (Vankov S., et al., 1973) and enhanced the ovulation of female rats (Vankov S. et al. 1973). Zarkova S. (1976) has also established in rats an increased number of spermatogonia, spermatocytes as well as increase of neutral mucopolysaccharides in seminiferous tubules of the testes. Gendzhev Z. and S. Zarkova, in other experiments (1978) proved the increase of spermatic reserve in the epididymis of rats.
With the view to the need of human medicine of a product stimulating sexual function, Tribestan was formulated on the base of the indicated phytochemical product. It contains saponins of furostanol type (Tomova M. et al., 1978). The first studies of Tribestan confirmed its high sex-stimulating activity in experimental animals (Zarkova S., 1981). Later, the clinical studies established a similar stimulating effect in humans as well (Protich M. at al. 1981). The present study was carried out with a view to throwing light on some aspects of the mechanism of that action of Tribestan, aiming at attaining an effect from the product on the serum concentration of some hypophyseal, sexual and adrenal hormones.
MATERIALS AND METHODS
The experiments were performed on 16 subjects (8 females and 8 males), aged 28-45. All subjects were in good health, without any complaints and good capacity for work. The following schedule was used:
1. The basic levels of hypophysiotropic hormones (ACTH, STH, LH, FSH), of sexual hormones (testosterone and estradiol) and of adrenal hormones (aldosterone and cortisol) were determined. They were determined twice, at 8 a.m. and 12 p.m. - one day prior to Tribestan treatment.
2. The treatment with the product was initiated on the following day, which was periodically administered, 250 mg, three times daily for 5 days.
3. After the termination of Tribestan treatment (day sixth after the initiation of the experiment), blood was again withdrawn (at the same hour - 8:00 a.m. and 12 p.m.) for the determination of the concentration of the indicated hormones.
The work proceeded in the following way: after centrifugation of 6 - 8 ml blood, the serum obtained was frozen at 20°C till the day of the determination of hormonal concentration. The determination was performed by radioimmune tests. LH and FSH were determined by the modified method of Midgley A.R., (1967), making use of some kits of Biodata company, Italy and ACTH and STH - according to the method of Berson S.A. and R. S. Yalow (1963). Testosterone was evaluated by the method of William R. H. (1968), and of estradiol by Orezyk G.P. et al. (1974), making use of kits of Sorin Company, Belgium for both hormones. The adrenal hormones cortisol and aldosterone were also determined by kits of that company, making use of Vescei P. (1974) and of William G and R. Hunderwood (1974).
The obtained results were statistically processed by variation analysis, by Student - t test.
RESULTS AND DISCUSSION
As could be seen from Table 1, LH level in the males was elevated with a high significance after the treatment (p < 0.001). The changes affected both samples to the same rate (at 8 a.m. and 12 p.m.). FSH concentration was not affected under the same conditions. The other two hypophyseal hormones, ACTH and STH were not changed.
An insignificant tendency to elevation was observed in STH level (mean values - 2.9 prior to and 3.2 mg/ml post treatment) in some of the cases. The level of sex hormones was strongly affected. Thus testosterone concentration was three-fold (2) increased and that of estradiol - about 1.5 times (Table 1).
Table 1
Hormone Prior to Tribestan
Post Tribestan
8 a.m.
12 p.m.
8 a.m.
12 p.m.
LH, mIU/ml X 13.0 14.38(1) 37.25 24.75
SX 0.64 0.73 1.01 0.79
Pt 0.001 0.001
FSH, mIU/ml X 13.38 13.50 13.38 11.38
SX 0.35 0.28 0.35 0.36
Pt >0.5 >0.5
Testosterone, ng % X 628 610 882 845
SX 48 46 35 32
Pt <0.001 <0.001
Estradiol pg/ml X 79 76 133 137.5
SX 3.46 2.24 6.72 5.86
Pt <0.001 <0.001
LH concentration was also increased in females under Tribestan effect. What impressed was that the significance was lower than the first sample. The greatest discrepancy, as compared with the results of the males, was the sharp stimulation of FSH. A strong effect was observed there, which could be explained by blood withdrawal during the early phase of the menstrual cycle, the so-called follicular phase. Estradiol was also strongly affected (Pt < 0.001), whereas testosterone in the females during the early hours of the day was less affected (Table 2).
Table 2
Hormone
Prior to Tribestan
Post Tribestan
8 a.m.
12 p.m.
8 a.m.
12 p.m.
LH, mIU/ml X 15.25 13.50 17.13 16.88
SX 0.64 0.87 0.73 0.35
Pt 0.02 0.001
FSH, mIU/ml X 11.00 11.88 17.75 15.25
SX 0.13 0.09 0.71 0.38
Pt 0.001 0.001
Estradiol mIU/ml X 72.13 59.38 77.13 87.50
SX 6.02 5.73 5.47 3.24
Pt 0.5 0.001
The level of adrenal hormone was identically affected both in males and females (Table 3). A significant increase of the concentration was also established though that effect had a relatively low significance (p < 0.05). At the same time, cortisol level was no changed (Table 3).
Table 3
Aldosterone Cortisol
Prior to Post Prior to Post
X 11.59 13.77 8.63 8.63
S 2.52 3.48 2.20 1.92
SX 0.63 0.87 0.55 0.48
Pt 0.05 0.05
The results obtained provided grounds to admit that Tribestan had a pronounced stimulating effect on the secretion of some hormones. The effect on the hormones along the hypophyseal-gonadal axis was particularly well manifested. The effect was manifested both at hypophyseal and gonadal level. Some sexual discrepancies were also established. Thus, FSH was mainly affected in the females. The presence of that hormone is exceptionally important during the follicular phase for the development of the follicle. When its development is stimulated, its secretory ability is also intensified and hence - estradiol level is elevated. Lutenizing hormone is more strongly influenced in the male, which on its part stimulates the secretion of testosterone.
ACTH and cortisol were not changed suggesting that they were not significantly involved in the realization of Tribestan effects. The tendency of stimulation of STH and aldosterone explained the activation of the anabolic processes in the body and general stimulating action of the product. The absence of effect on the level of cortisol showed however that the general tonic action was very strongly manifested.
It should be stressed that the level of the hormones studied did not go out beyond the physiological frames i.e. it did not disturb the physiological mechanisms of hormonal regulation.
References
Vankov S., S. Zarkova, Z. Gendzhev, M. Tomova - Effect of TB-68 on the spermatogenesis in albino rats. Proceeding of the Third National Conference of Pharmacology and Clinics of New Bulgarian Drugs, Sofia, November 14-16, 1973, v.2, 161-163.
Vankov S., S. Zarkova, M. Tomova - TB-68 effect on ovulation of albino rats. Proceedings of Third National Conference of Pharmacology and Clinics of New Bulgarian Drugs, Sofia, November 14-16, 1973, v.2, 165-167.
Gendzhev Z., S. Zarkova - Effect of the phyto-pharmaceutical TB-68 on the number of spermatozoa in epididymis of rat. Med. Archive, 1978, N I, 113-118.
Dimova P., M. Taskov - Comparative enzyme-histological studies of some phyto-products. MBI (at the printer's), 1981.
Zarkova S. - Morphological and histological changes in testes of rat under the effect of TB-68, Med. Archive, 1976, N 4, 49-53.
Protich M., D. Zvetanov, V. Nalbanski, R.Stanislavov, M.Kazarova - Clinical trial of Tribestan on infertile males, MBI (at the printer's).
Tomova M., V. Gyulemetova, S. Zarkova - Author's certificate N 77584 A 61 K 35/1978.
Berson S.A., R. S. Yalow - Immunoassay of protein hormones, The Hormones, Vol. V, Acad. Press., New York, 1963.
Midgley A.R. - Radioimmunoassay for Human, J. Clin. Endocr., 1967, 27, 295.
Orezyk, Gaylo P., Burton v. Caldwell, Harold H. Behrmaan - Methods of Hormone Radioimmunoassay - Ed. B. Jaffe, H. Berhmaan, A6. Press, NJ, London, 1974, 333-343.
Vescei P. - Glicocorticoids: Cortisol Corticosterone - Methods of Hormone Radioimmunoassay; Ed. B. Jaffe and H. Behrmaan, Ac. Press, NJ, London 393-412.
William R.H. - Textbook of Endocrinology 4th Edit. Saunder, Philadelphia, 1968.
Williams Gordon H., Richard H. Hunderwood - Methods of Hormon Radioimmunoassay; Ed. B. Jaffe and H. Behrmaan, Ac. Press, NJ, London, 1974, 371-390.
Aphrodisiac properties of Tribulus Terrestris extract (Protodioscin) in normal and castrated rats.Gauthaman K, Adaikan PG, Prasad RN.
Department of Obstetrics and Gynaecology, National University Hospital, National University of Singapore, Singapore 119704, Singapore.
Tribulus terrestris (TT) has long been used in the traditional Chinese and Indian systems of medicine for the treatment of various ailments and is popularly claimed to improve sexual functions in man. Sexual behaviour and intracavernous pressure (ICP) were studied in both normal and castrated rats to further understand the role of TT containing protodioscin (PTN) as an aphrodisiac. Adult Sprague-Dawley rats were divided into five groups of 8 each that included distilled water treated (normal and castrated), testosterone treated (normal and castrated, 10 mg/kg body weight, subcutaneously, bi-weekly) and TT treated (castrated, 5 mg/kg body weight, orally once daily). Decreases in body weight, prostate weight and ICP were observed among the castrated groups of rats compared to the intact group. There was an overall reduction in the sexual behaviour parameters in the castrated groups of rats as reflected by decrease in mount and intromission frequencies (MF and IF) and increase in mount, intromission, ejaculation latencies (ML, IL, EL) as well as post-ejaculatory interval (PEI). Compared to the castrated control, treatment of castrated rats (with either testosterone or TT extract) showed increase in prostate weight and ICP that were statistically significant. There was also a mild to moderate improvement of the sexual behaviour parameters as evidenced by increase in MF and IF; decrease in ML, IL and PEI. These results were statistically significant. It is concluded that TT extract appears to possess aphrodisiac activity probably due to androgen increasing property of TT (observed in our earlier study on primates).
The hormonal effects of Tribulus terrestris and its role in the management of male erectile dysfunction - an evaluation using primates, rabbit and rat.
Gauthaman K, Ganesan AP.
Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, 119074 Singapore.
Hormonal effects of Tribulus terrestris (TT) were evaluated in primates, rabbit and rat to identify its usefulness in the management of erectile dysfunction (ED). TT extract was administered intravenously, as a bolus dose of 7.5, 15 and 30mg/kg, in primates for acute study. Rabbits and normal rats were treated with 2.5, 5 and 10mg/kg of TT extract orally for 8 weeks, for chronic study. In addition, castrated rats were treated either with testosterone cypionate (10mg/kg, subcutaneously; biweekly for 8 weeks) or TT orally (5mg/kg daily for 8 weeks). Blood samples were analyzed for testosterone (T), dihydrotestosterone (DHT) and dehydroepiandrosterone sulphate (DHEAS) levels using radioimmunoassay. In primates, the increases in T (52%), DHT (31%) and DHEAS (29%) at 7.5mg/kg were statistically significant. In rabbits, both T and DHT were increased compared to control, however, only the increases in DHT (by 30% and 32% at 5 and 10mg/kg) were statistically significant. In castrated rats, increases in T levels by 51% and 25% were observed with T and TT extract respectively that were statistically significant. TT increases some of the sex hormones, possibly due to the presence of protodioscin in the extract. TT may be useful in mild to moderate cases of ED.
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Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo- controlled double-blind study.
M Halaska , P Beles , C Gorkow , C Sieder
In a placebo-controlled, randomized, double-blind study the efficacy of a Vitex agnus castus extract-containing solution* (VACS) was investigated in patients suffering from cyclical mastalgia. Patients had mastalgia on at least 5 days in the pre-treatment cycle. During this cycle and during treatment (3 cycles; 2 x 30 drops/day), the intensity of mastalgia was recorded once per cycle using a visual analogue scale (VAS).After one/two treatment cycles, the mean decrease in pain intensity (mm, VAS) was 21.4 mm /33.7 mm in women taking VACS (n= 48) and 10.6 mm/20.3 mm with placebo (n=49). The differences of the VAS-values for VACS were significantly greater than those with placebo (p= 0.018;p= 0.006). After three cycles, the mean VAS-score reduction for women taking VACS was 34.3 mm, a reduction of 'borderline significance' (p= 0.064) on statistical testing compared with placebo (25.7 mm). There was no difference in the frequency of adverse events between both groups (VACS:n = 5; placebo: n= 4). VACS appears effective and was well tolerated and further evaluation of this agent in the treatment of cyclical mastalgia is warranted.
[Effectiveness of Vitex agnus-castus preparations]
C Gorkow , W Wuttke , R W März
The prolactin-inhibiting effect of ACF-preparations, which is due to dopaminergic activities, has been shown in humans too and gives a pharmacological rationale for the clinical effects observed in the different indications (2, 11, 25, 26, 35, 41). Confirmation of efficacy in the treatment of mastalgia has been best endorsed by two recently published double-blind studies conducted according to the principles of GCP (14, 41). One double-blind study, several open and postmarketing surveillance studies have shown that the premenstrual syndrome, or individual symptoms, can be influenced positively (3, 6, 7, 9, 19, 21, 37). Design shortcomings in a second double-blind study should be eliminated in future studies in this indication to improve the body of evidence (18). Hither to there has been one controlled double-blind study of cycle disorders in the case of corpus luteum insufficiency with significant results and a number of non-controlled open studies (1, 4, 15, 16, 20, 24, 26, 27, 32, 35, 36). The high success rates in the open studies indicate therapeutic effects, and it should be possible to reproduce these results under double-blind conditions. The success rates on fertility disorders should be confirmed in controlled double- blind studies (10, 33, 34).
The effects of a special Agnus castus extract (BP1095E1) on prolactin secretion in healthy male subjects.
P G Merz , C Gorkow , A Schrödter , S Rietbrock , C Sieder , D Loew , J S Dericks-Tan , H D Taubert
The effects of three doses of a special Agnus castus extract (BP1095E1)--extracts from 120 mg, 240 mg and 480 mg of drug per day--were examined within the framework of a placebo-controlled clinical study of tolerance and prolactin secretion in 20 healthy male subjects during a period of 14 days. There was good tolerance during the study as regards the following: adverse effects, the effects on blood pressure and heart rate, blood count, Quick's test, clinical chemistry as well as testosterone, FSH and LH values. During each study phase the 24-hour prolactin secretion profile was measured from the penultimate to the final day, and the amount of prolactin release was monitored an hour after TRH stimulation on the last day. A significant increase in the 24-hour profile was registered with the lowest dose in comparison to placebo, the opposite being the case with the higher doses, i.e. a slight reduction. In contrast to the administration of placebo, the 1-hour AUC after TRH stimulation resulted in a significant increase with the lowest dose and a significant reduction with the highest dose. The results suggest effects of the special Agnus castus extract which are dependent on the dose administered and the initial level of prolactin concentration.
English Title: Evidence for estrogen receptor β-selective activity of Vitex agnus-castus and isolated flavones.
Personal Authors: Jarry, H., Spengler, B., Porzel, A., Schmidt, J., Wuttke, W., Christoffel, V.
Author Affiliation: Abteilung für Klinische und Experimentelle Endokrinologie, Universitätsfrauenklinik Göttingen, Robert Koch-Strasse 40, 37075 Göttingen, Germany.
Editors: No editors
Document Title: Planta Medica, 2003 (Vol. 69) (No. 10) 945-947
Abstract:
Recent cell culture experiments indicated that extracts of V. agnus-castus (VAC) may contain yet unidentified phytoestrogens. Estrogenic actions are mediated via oestrogen receptors (ER). To investigate whether VAC compounds bind to the currently known isoforms ERα or ERβ, ligand-binding assays (LBA) were performed. Subtype specific ER-LBA revealed a binding of VAC to ERβ only. To isolate the ERβ-selective compounds, the extract was fractionated by bio-guidance. The flavonoid apigenin was isolated and identified as the most active ERβ-selective phytoestrogen in VAC. Other isolated compounds were vitexin and penduletin. These data demonstrate that the phytoestrogens in VAC are ERβ-selective.
Vitex agnus castus L., - traditional drug and actual indications
Karl Peter Odenthal *
Pharmacology, Experimental Research, Madaus AG, Ostmerheimerstraße 198, D-51101 Köln, Germany
*Correspondence to Karl Peter Odenthal, Pharmacology, Experimental Research, Madaus AG, Ostmerheimerstraße 198, D-51101 Köln, Germany
Abstract
There is a long tradition for the use of different preparations of drugs of Vitex agnus castus in complementary medicine in Europe. The indications in disorders of the female sexual cycle have been confirmed by experimental and clinical results. The activity of hitherto unidentified constituents of the ethanol seed extract could be localized within the pituitary-gonadal axis. Research in pituitary cell assays further elucidated a dopaminergic inhibition of prolactin synthesis and/or release. The effective administration of ethanol seed extracts against mastodynia and symptoms related to female cycle disorders with concomitant hyperprolactinaemia has been documented and awaits further establishment. © 1998 John Wiley & Sons, Ltd.
Vitex and Dopaminergic Activity
Prolactin secretion from the anterior pituitary is under the dual control of a yet unknown hypothalamic factor which stimulates prolactin release and the catecholamine dopamine which acts as a prolactin inhibiting factor. Several intrinsic (e.g. sleep) and exogenous (e.g. stress) stimuli enhance prolactin release. The prolactin-producing cells of the pituitary, the lactotropes, express the D2 subtype of the dopamine-receptor which is coupled to adenylate cyclase. Activation of the D2 receptor by either dopamine or compounds related in their molecular structure to dopamine reduces the synthesis of cAMP resulting in an inhibition of prolactin secretion. Prolactin has numerous targets in the body, among them the mammary glands and the corpus luteum. While a hyposecretion of prolactin appears to be without pathophysiological consequences, an excessive release of prolactin causes fertility disorders like corpus luteum insufficiency. Premenstrual symptoms (PMS) like breast tenderness might be associated with the s o-called "latent" hypersecretion of prolactin, i.e. in response to a stimulus, the lactotropes release supraphysiological amounts of prolactin. As a consequence the mammary gland tissue is stimulated subchronically which causes the symptom of mastalgia (breast pain). Recent research attention has focussed on the dopaminergic activity of Vitex agnus castus (chaste tree) in an attempt to explain its action in PMS and its general activity in regulating female hormonal function. One German research team reviewed at Munich their work to date in this area. [1] Both clinical and in vitro studies demonstrated a prolactin-inhibiting activity in Vitex, in particular on stimulated prolactin release. In vitro the dopamine-antagonist haloperidol counteracted this effect which confirms the assumption that Vitex contains constituents which inhibit prolactin release via interaction with the D2-subtype of the dopamine receptor. During the bioguided fractionation of Vitex using prolactin release in pituitary cell cultures and binding of test compounds to isolated D2 receptors, it became evident that Vitex contains at least two different types of dopaminergic compounds: hydrophilic, thermolabile dopamine agonists but also lipophilic, more thermostable endocrine active compounds. The latter type of substances could be identified as bicyclic diterpenes. These diterpenes inhibit cAMP-production and thereby prolactin release with a virtually equimolar potency to dopamine. The purification of the hydrophilic dopaminergic principle in Vitex is currently in progress. The same team then went on to describe their assessment of the dopaminergic activity of Vitex products on the German market. [2] Commercially available preparations of Vitex are prepared from the fruits using water/ethanol mixtures as the excipient. The percentage of ethanol in the marketed formulation ranges from 0 to 60%. Therefore, it is very likely that formulations which contain high, low or even no ethanol will also contain different amounts of the prolactin lowering activity. To test this assumption three different lots of nine liquid Vitex preparations commercially available in Germany were bought at a public pharmacy and were examined for their dopaminergic potency in the D2-receptor binding assay (DRBA). The highest ethanol content (v/v) in the formulations was 70%, the lowest 0%. The dopaminergic potency was determined as a [micro]M concentration of dopamine which causes the same displacement in the binding assay as the test product. There was about a 100-fold difference in the dopaminergic potenc y between formulations tested. Since the two most active preparations contained additives, these ingredients were also examined for displacement capacity in the DRBA. None of these additives exerted a significant activity in this assay system. Although it has not been conclusively proven that dopaminergic activity is essential for clinical success with Vitex preparations, these large discrepancies in activity are certainly cause for concern.
References
(1.) Jarry H, Spengler B, Wuttke W at al. Phytotherapy in gynecology; pharmacological rationale for the use of dopaminergic principles. Paper presented at the 3rd International Congress on Phytomedicine, Munich, October 11 to 13,2000 (SL-6a).
(2.) Jarry H, Metten M, Wuttke W. Comparison of the dopaminergic potency of various commercially available Agnus-castus preparations: the need for biological standardization. Paper presented at the 3rd International Congress on Phytomedicine, Munich, October 11 to 13,2000 (SL-6b).