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Currently the most popular post cycle therapy ingriedient is a compound called ATD (Our ATD product is Rebound XT). Some companies list ATD as 3, 17-keto-etiochol-triene or 3,17-Dioxoetioallocholan-1,4,6-triene. These same products have claims like “ clinical trials show our product increases bioavailable testosterone significantly higher (over 400%) and faster (within 2 weeks) than any other testosterone booster in the supplement industry.”
Sure, ATD based products have been clinically shown to increase total and free testosterone as much as 400 or even 600%. And we have read countless times that it is the best aromatase inhibitor (anti-estrogen) on the planet. But is it doing anything really?
Clinical studies are nice when they are paid for by a manufacturer, but there are two questions we need to consider in the world the rest of us live in:
1) If testosterone is the hormone that makes us horny (increased libido), then why is it that users with testosterone levels at 400-600% above normal have such a low libido? It is very common for people using ATD products to completely lose their sex drive.
2) Since ATD is such a wonderful anti-aromatase (anti-estrogen), we need to ask why so many users are reporting gynocomastia? (Gyno is caused by high estrogen levels or hormone environments that allow estrogen activity to exceed testosterone activity)
Now let’s find out why ATD has the negative side affects that are totally opposite of supposed dramatic testosterone levels? Several studies quoted below will answer these question.
A research team in Amsterdam had an interesting finding related to ATD…
(3) "Rats treated with ATD in both pre- and postnatal periods showed 'bisexual' partner preference.
Regular ATD products may have a sexual preference altering affect upon male mammals.
(4) "When the choice was between an estrous female and an ATD-male, partner PS decreased in all males, most clearly in ATD-males."
(5)"… again revealing the behavioral bisexual nature of these ATD males. A new finding was the much higher locomotor activity of the ATD males compared to controls"
Just because some mammals change sexual preference does not necessarily make it conclusive that humans will. But what about actual human users of ATD having trouble with erections with all of that “extra” testosterone from ATD?
The Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands did another study on the affects of ATD on mammals with an increase in total daily dosage that lead to this finding:
(6) "Combined pre- and neonatal ATD treatment resulted in reduced frequency of mounts, intromissions, and ejaculations, as well as a reduced preference for a female over a male"
This appears to be the result of an affect ATD directly has on the body. Bottom line this is not a positive response. But what about all of that extra testosterone (400% more) ATD causes in most users, and why would it have these really negative side affects?
In a study titled "Effects of ATD on male sexual behavior and androgen receptor binding." the answer is clear.
(7) "ATD, has been found to suppress male sexual behavior in T-treated mammals. In our experiment, we first replicated this finding by peripherally injecting ATD (15 mg/day)"
This shows that ATD suppresses normal male functions, but why no new muscle but plenty of gyno if the testosterone levels are so high?
(7) "In all four brain areas binding of T to androgen receptors was significantly decreased in the presence of ATD, suggesting that ATD may act both as an androgen receptor blocker and as an aromatization inhibitor. Competitive binding studies indicated that ATD competes in vitro for cytosol androgen receptors, thus substantiating the in vivo antiandrogenic effects of ATD"
Proof that ATD is not only an anti-androgen, but it competes with all of that 400-600% extra testosterone for binding to the androgen receptors. That means that any amount of estrogen in your body takes over and you get gyno.
(7) "No agonistic properties of ATD were observed either behaviorally or biochemically. Thus, an alternative explanation for the inhibitory effects of ATD on male sexual behavior is that ATD prevents T from binding to androgen receptors.
The negative ATD actions described above might not be experienced by everyone. Anabolic Xtreme does carry a 100% regular ATD based product Rebound XT™ that we stand behind. BUT if you are unsure how your body reacts to ATD or have any doubt, PCT™ is the product you should choose.
PCT™ is not a regular ATD based product…….it works!
Long ago researchers discovered that hydroxylation of ATD at carbon 17 results in a better compound that does not block all the androgen receptors in the whole body like regular ATD. The natural compound is a cousin of ATD made in the brain called 1,4,6-Androstatriene-17-ol-3-one. The only problem was that it was that it had very poor oral bioavailability. So Anabolic Xtreme took this poorly absorbed compound and attached a non liver toxic methyl group to the compound. By attaching the methyl group it makes the compound absorbed very well when taken orally (pill). We named this compound mATD.
1) Flesinoxan: a prosexual drug for male rats.
Eur J Pharmacol. 1997 Jul 2;330(1):1-9.
Eur J Pharmacol. 1997 Jul 2;330(1):1-9.
Related Articles, Links
Click here to read
Flesinoxan: a prosexual drug for male rats.
Haensel SM, Slob AK.
Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University and Dijkzigt Academic Hospital, Rotterdam, Netherlands. [email protected]
Two tests were carried out to compare the stimulatory (i.e., prosexual) effects of the 5-HT1A receptor agonists flesinoxan and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on sexual behavior in male Wistar rats. Two groups of rats were used: normal males and males with impaired masculine sexual behavior due to neonatal treatment with the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD). In Experiment 1, flesinoxan (0.3 and 1.0 mg/kg) stimulated ejaculation frequency and number of animals displaying this behavior, both in controls and ATD males. With 0.3 mg/kg flesinoxan ATD males did not differ from controls in ejaculation frequencies. There was a concomitant decrease in latency to first ejaculation. No 'premature' ejaculations (i.e., at first or second intromission) were observed. In Experiment 2, the effects of 0.4 mg/kg 8-OH-DPAT, 0.3, 1.0 and 3.0 mg/kg flesinoxan and saline were tested in two ejaculation series. 'Premature' ejaculations only occurred during first ejaculation series with 8-OH-DPAT in 8 of 10 controls and in 6 of 9 ATD males; it did not occur during flesinoxan treatment nor in the second ejaculation series with 8-OH-DPAT treatment. Thus, flesinoxan stimulates sexual behavior in control rats and in rats with impaired sexual behavior. Unlike 8-OH-DPAT flesinoxan does not render them into 'premature' ejaculators. Therefore, flesinoxan could be considered a prosexual drug for male rats.
(2) Endogenous reproductive hormones and nocturnal rhythms in partner preference and sexual behavior of ATD-treated male rats.
Neuroendocrinology. 1995 Oct;62(4):396-405.
Neuroendocrinology. 1995 Oct;62(4):396-405.
Related Articles, Links
Endogenous reproductive hormones and nocturnal rhythms in partner preference and sexual behavior of ATD-treated male rats.
Bakker J, van Ophemert J, Timmerman MA, de Jong FH, Slob AK.
Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands .
Male rats received subcutaneously silastic capsules, containing the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD), shortly after birth. Control males were given silastic capsules containing cholesterol. The capsules were removed at the age of 21 days. In adulthood, blood serum was collected early and late in the dark phase of the light/dark cycle (experiment I). Testosterone and luteinizing hormone and follicle stimulating hormone (FSH) fluctuated nocturnally, both in ATD and control males, with highest levels late in the dark phase. FSH levels were significantly higher in ATD males. Nocturnal levels of inhibin, a selective suppressor of pituitary FSH secretion, also fluctuated in both ATD and control males, with lowest levels late in the dark phase. In experiment II, ATD and control males were tested for partner preference behavior in a three-compartment box (choice: sexually active male vs. estrous female) early and late in the dark phase. When gonadally intact, ATD males, but not controls, showed a clear nocturnal rhythmicity in partner preference behavior and sexual behavior. Early in the dark phase, such ATD males preferred the vicinity of and interaction with a sexually active male. Late in the dark phase, this preference for the active male shifted to a preference for the estrous female. Control males preferred the estrous female. After castration and subsequent treatment with testosterone via silastic capsules, which ensured constant blood serum levels, ATD males continued to show their nocturnal rhythms in partner preference behavior and in sexual behavior. Thus, the underlying mechanism of the nocturnal rhythmicity phenomenon is an organizational effect of neonatal ATD treatment rather than an activational effect of fluctuating serum hormone levels.
(3) Increased number of vasopressin neurons in the suprachiasmatic nucleus (SCN) of 'bisexual' adult male rats following perinatal treatment with the aromatase blocker ATD.
Brain Res Dev Brain Res. 1995 Apr 18;85(2):273-9.
Related Articles, Links
Click here to read
Increased number of vasopressin neurons in the suprachiasmatic nucleus (SCN) of 'bisexual' adult male rats following perinatal treatment with the aromatase blocker ATD.
Swaab DF, Slob AK, Houtsmuller EJ, Brand T, Zhou JN.
Netherlands Institute for Brain Research, Graduate School Neurosciences Amsterdam .
In an earlier article an enlarged subpopulation of vasopressin containing neurons was found in the suprachiasmatic nucleus (SCN) of homosexual men as compared to heterosexuals. The present study investigates the possibility that the number of vasopressin neurons in the SCN and sexual partner preference behavior in male rats are both influenced by sex hormones during brain development. For this purpose, we studied groups of adult male rats that had been treated either prenatally or pre- and postnatally with the aromatase inhibitor ATD (1,4,6-androstatriene-3,17-dione) which blocks the aromatization of testosterone to estradiol. Rats treated with ATD in both pre- and postnatal periods showed 'bisexual' partner preference behavior and appeared to have 59% more vasopressin-expressing neurons in the SCN than the controls. The prenatally treated rats did not differ from the controls. This observation supports the hypothesis that the increased number of vasopressin neurons found earlier in the SCN of adult homosexual men might reflect differences that took place in the interaction between sex hormones and the brain early in development.
(4) Postweaning housing conditions and partner preference and sexual behavior of neonatally ATD-treated male rats.
Psychoneuroendocrinology. 1995;20(3):299-310.
Psychoneuroendocrinology. 1995;20(3):299-310.
Related Articles, Links
Postweaning housing conditions and partner preference and sexual behavior of neonatally ATD-treated male rats.
Bakker J, van Ophemert J, Slob AK.
Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands .
Male rats were neonatally treated with cholesterol or a substance that blocks the aromatization of testosterone to estradiol (1,4,6-androstatriene-3,17-dione: ATD). At weaning (21 days) they were either housed alone or in small groups (2-3 animals) and tested for partner preference behavior (PPB) in adulthood. Choice was between an estrous female and an active male (Part I) and between an estrous female and an ATD-male (Part II). Tests were carried out in a 3-compartment box. Social isolation did not have major effects on PPB except when sexual interaction with the stimulus animals was prevented (Part I). In this case, isolates (ATD and control) showed higher preference scores (PS) for the estrous female and spent less time in the empty middle compartment. When the choice was between an estrous female and an ATD-male, partner PS decreased in all males, most clearly in ATD-males. The latter animals spent more time with the stimulus ATD-male than they had done in previous PPB tests with the normal stimulus male. In contrast to partner preference behaviors, sexual behavior was clearly affected by social isolation. Isolates (ATD and control) displayed lower frequencies of mounts and intromissions. These effects persisted over consecutive tests. Ejaculation was not affected. In conclusion, the present results confirm earlier findings about the significance of neonatal endocrine conditions for the organization of adult PPB in male rats. The presence or absence of social conspecifics after weaning appears to have little influence on adult PPB.
(5) A semiautomated test apparatus for studying partner preference behavior in the rat.
Physiol Behav. 1994 Sep;56(3):597-601.
Physiol Behav. 1994 Sep;56(3):597-601.
Related Articles, Links
A semiautomated test apparatus for studying partner preference behavior in the rat.
Bakker J, van Ophemert J, Eijskoot F, Slob AK.
Department of Endocrinology and Reproduction, Erasmus University, Rotterdam, The Netherlands .
A semiautomated three-compartment box (3CB) for studying partner preference behavior of rats is described. This apparatus automatically records the rat's time spent in each compartment, as well as the locomotor activity (i.e., the number of visits an animal pays to each compartment). Software was developed for calculating partner preference scores. Behavioral testing in the semiautomated 3CB, which is a modification of an earlier version, is less time consuming and less laborious. Three 3CBs can be observed simultaneously by two trained observers, and the behavioral interactions of three experimental animals with the stimulus animals can be observed and scored by hand. The use of the new apparatus was validated by studying adult partner preference behavior of neonatally ATD-treated male rats. The collected data fully corroborate previous results, obtained in the earlier version of the 3CB, again revealing the behavioral bisexual nature of these ATD males. A new finding was the much higher locomotor activity of the ATD males compared to controls.
(6) SDN-POA volume, sexual behavior, and partner preference of male rats affected by perinatal treatment with ATD.
Physiol Behav. 1994 Sep;56(3):535-41.
Physiol Behav. 1994 Sep;56(3):535-41.
Related Articles, Links
SDN-POA volume, sexual behavior, and partner preference of male rats affected by perinatal treatment with ATD.
Houtsmuller EJ, Brand T, de Jonge FH, Joosten RN, van de Poll NE, Slob AK.
Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands .
The present study investigated 1) the importance of the aromatization process during the perinatal period for the development of the sexually dimorphic nucleus in the preoptic area of the hypothalamus (SDN-POA) of male rats, and 2) the relationship between SDN-POA volume and parameters of masculinization in male rats that were treated perinatally with the aromatase-inhibitor ATD. Males were treated with ATD either prenatally or pre- and neonatally, or with the vehicle. Masculine sexual behavior and partner preference were investigated in adulthood. Thereafter, animals were sacrificed and SDN-POA volume was measured. The SDN-POA volume was reduced in both the prenatally and the pre- and neonatally treated group, with a larger reduction in the latter than in the former group. Combined pre- and neonatal ATD treatment resulted in reduced frequency of mounts, intromissions, and ejaculations, as well as a reduced preference for a female over a male. The SDN-POA size was significantly and positively correlated with frequency of masculine sexual behavior, as well as preference for a female over a male.
(7) Effects of ATD on male sexual behavior and androgen receptor binding: a reexamination of the aromatization hypothesis.
Horm Behav. 1989 Mar;23(1):10-26.
Horm Behav. 1989 Mar;23(1):10-26.
Related Articles, Links
Effects of ATD on male sexual behavior and androgen receptor binding: a reexamination of the aromatization hypothesis.
Kaplan ME, McGinnis MY.
Department of Anatomy, Mount Sinai School of Medicine, CUNY, New York 10029.
The aromatization hypothesis asserts that testosterone (T) must be aromatized to estradiol (E2) to activate copulatory behavior in the male rat. In support of this hypothesis, the aromatization inhibitor, ATD, has been found to suppress male sexual behavior in T-treated rats. In our experiment, we first replicated this finding by peripherally injecting ATD (15 mg/day) or propylene glycol into T-treated (two 10-mm Silastic capsules) or control castrated male rats. In a second experiment, we bilaterally implanted either ATD-filled or blank cannulae into the medial preoptic area (MPOA) of either T-treated or control castrated male rats. With this more local distribution of ATD, a lesser decline in sexual behavior was found, suggesting that other brain areas are involved in the neurohormonal activation of copulatory behavior in the male rat. To determine whether in vivo ATD interacts with androgen or estrogen receptors, we conducted cell nuclear androgen and estrogen receptor binding assays of hypothalamus, preoptic area, amygdala, and septum following treatment with the combinations of systemic T alone. ATD plus T, ATD alone, and blank control. In all four brain areas binding of T to androgen receptors was significantly decreased in the presence of ATD, suggesting that ATD may act both as an androgen receptor blocker and as an aromatization inhibitor. Competitive binding studies indicated that ATD competes in vitro for cytosol androgen receptors, thus substantiating the in vivo antiandrogenic effects of ATD. Cell nuclear estrogen receptor binding was not significantly increased by exposure to T in the physiological range. No agonistic properties of ATD were observed either behaviorally or biochemically. Thus, an alternative explanation for the inhibitory effects of ATD on male sexual behavior is that ATD prevents T from binding to androgen receptors.
Differential effects of aromatase inhibition on luteinizing hormone secretion in intact and castrated male cynomolgus macaques.
J Clin Endocrinol Metab. 1993 Dec;77(6):1529-34.
J Clin Endocrinol Metab. 1993 Dec;77(6):1529-34.
Related Articles, Links
Differential effects of aromatase inhibition on luteinizing hormone secretion in intact and castrated male cynomolgus macaques.
Resko JA, Connolly PB, Roselli CE, Abdelgadir SE, Choate JV.
Department of Physiology, Oregon Health Sciences University, Portland 97201-3098.
To understand the role of central aromatization in feedback regulation of LH in nonhuman primates, we treated adult male cynomolgus monkeys with the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD). We measured LH, testosterone (T), and ATD in systemic sera of blood samples drawn on a diurnal schedule (0900 and 2100 h). Each animal was bled for 4 pretreatment days from a femoral catheter after which they were divided into the following treatment groups: castrated (Cx), n = 2; Cx + T, n = 6; Cx + T + ATD, n = 6; Cx + ATD, n = 3; and sham operated + ATD, n = 3. Silastic capsules or packets containing T or ATD, respectively, were placed sc between the scapulae at the time of Cx or sham treatment. In T-treated animals, T (20 micrograms/kg body weight) dissolved in propylene glycol was injected im at 2100 h to mimic the diurnal rise of T observed in nonhuman primates. Animals were bled for 2 weeks after which they were killed, and selected brain areas were analyzed for aromatase activity and cytosolic and nuclear androgen receptors. Animals treated with ATD had significantly reduced levels of aromatase activity in selected regions of the hypothalamus, preoptic area, and the amygdala (P < 0.05). Even though ATD inhibited brain aromatase activity, it did not prevent the negative feedback actions of T on LH secretion after Cx. In addition, ATD by itself inhibited LH secretion after Cx and activated brain androgen receptors. These latter effects of ATD seemed to have been mediated through a metabolite. In sham-operated intact males, ATD produced variable surges of LH that were accompanied by elevations of T in the systemic circulation. These differential effects of ATD in intact vs. castrated animals demonstrate the importance of selecting the proper model system to study LH control mechanisms. In the intact animal, aromatization seems to play a role in regulating LH secretion, but the postcastration rise of LH seems to be regulated differently.
Studies on aromatase inhibition with 4-androstene-3,6,17-trione: its 3 beta-reduction and time-dependent irreversible binding to aromatase with human placental microsomes.
Steroid Biochem. 1987 Sep;28(3):337-44.
Related Articles, Links
Studies on aromatase inhibition with 4-androstene-3,6,17-trione: its 3 beta-reduction and time-dependent irreversible binding to aromatase with human placental microsomes.
Numazawa M, Tsuji M, Mutsumi A.
Tohoku College of Pharmacy, Sendai, Japan.
The metabolism of 4-androstene-3,6,17-trione (AT), previously described as a suicide substrate for aromatase, and its irreversible binding to aromatase were studied by using human placental microsomes. AT was rapidly converted into 3 beta-reduced metabolite (3-OHAT) with an enzyme other than aromatase in the microsomes in the presence of NADPH under either aerobic or anaerobic conditions. The conversion was efficiently prevented by a steroid 5 alpha-reductase inhibitor. 3-OHAT was characterized as a competitive (Ki = 6.5 microM) and irreversible inhibitor of aromatase. Both 14C-labeled AT and 3-OHAT were demonstrated to be irreversibly bound to aromatase probably through a sulfur atom of the enzyme in time-dependent manners in the presence of NADPH, being accompanied with time-dependent losses of the enzyme activity. It was shown that the process of an apparent time-dependent loss of aromatase activity caused by AT even under conditions allowing its 3 beta-reduction should principally depend on the action of the parent inhibitor AT itself and not on that of the metabolite 3-OHAT.
Detection of androst-4-ene-3,6,17-trione (6-OXO) and its metabolites in urine by gas chromatography-mass spectrometry in relation to doping analysis.
Biomed Chromatogr. 2005 Nov;19(9):689-95.
Related Articles, Links
Click here to read
Detection of androst-4-ene-3,6,17-trione (6-OXO) and its metabolites in urine by gas chromatography-mass spectrometry in relation to doping analysis.
Van Thuyne W, Van Eenoo P, Mikulcikova P, Deventer K, Delbeke FT.
Doping Control Laboratory, Department of Clinical Biology, Microbiology and Immunology, Ghent University-UGent, Technologiepark 30, B-9052 Zwijnaarde, Belgium.
The metabolism and excretion of androst-4-ene-3,6,17-trione after administration of the 'nutritional' supplement 6-OXO was investigated by gas chromatography-mass spectrometry (GC-MS) in full-scan mode. The parent drug androst-4-ene-3,6,17-trione and androst-4-ene-6alpha,17beta-diol-3-one and androst-4-ene-6alpha-ol-3,17-dione were detected in the post-administration urine samples. Because androst-4-ene-3,6,17-trione is an anabolic steroid and an aromatase inhibitor, this substance is regarded as a doping agent. Hence, a selective and sensitive GC-MS method in selected ion monitoring mode for the detection of the TMS-enol-TMS-ether derivatives of these substances was developed and validated for doping control purposes. The limit of detection (LOD) of the investigated compounds ranged from 5 to 10 ng/mL. Using this method, the detection time for androst-4-ene-3,6,17-trione and androst-4-ene-6alpha,17beta-diol-3-one was 24 h, while androst-4-ene-6alpha-ol-3,17-dione could be detected up to 37 h after administration of the dose recommended by the manufacturer.
Sure, ATD based products have been clinically shown to increase total and free testosterone as much as 400 or even 600%. And we have read countless times that it is the best aromatase inhibitor (anti-estrogen) on the planet. But is it doing anything really?
Clinical studies are nice when they are paid for by a manufacturer, but there are two questions we need to consider in the world the rest of us live in:
1) If testosterone is the hormone that makes us horny (increased libido), then why is it that users with testosterone levels at 400-600% above normal have such a low libido? It is very common for people using ATD products to completely lose their sex drive.
2) Since ATD is such a wonderful anti-aromatase (anti-estrogen), we need to ask why so many users are reporting gynocomastia? (Gyno is caused by high estrogen levels or hormone environments that allow estrogen activity to exceed testosterone activity)
Now let’s find out why ATD has the negative side affects that are totally opposite of supposed dramatic testosterone levels? Several studies quoted below will answer these question.
A research team in Amsterdam had an interesting finding related to ATD…
(3) "Rats treated with ATD in both pre- and postnatal periods showed 'bisexual' partner preference.
Regular ATD products may have a sexual preference altering affect upon male mammals.
(4) "When the choice was between an estrous female and an ATD-male, partner PS decreased in all males, most clearly in ATD-males."
(5)"… again revealing the behavioral bisexual nature of these ATD males. A new finding was the much higher locomotor activity of the ATD males compared to controls"
Just because some mammals change sexual preference does not necessarily make it conclusive that humans will. But what about actual human users of ATD having trouble with erections with all of that “extra” testosterone from ATD?
The Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands did another study on the affects of ATD on mammals with an increase in total daily dosage that lead to this finding:
(6) "Combined pre- and neonatal ATD treatment resulted in reduced frequency of mounts, intromissions, and ejaculations, as well as a reduced preference for a female over a male"
This appears to be the result of an affect ATD directly has on the body. Bottom line this is not a positive response. But what about all of that extra testosterone (400% more) ATD causes in most users, and why would it have these really negative side affects?
In a study titled "Effects of ATD on male sexual behavior and androgen receptor binding." the answer is clear.
(7) "ATD, has been found to suppress male sexual behavior in T-treated mammals. In our experiment, we first replicated this finding by peripherally injecting ATD (15 mg/day)"
This shows that ATD suppresses normal male functions, but why no new muscle but plenty of gyno if the testosterone levels are so high?
(7) "In all four brain areas binding of T to androgen receptors was significantly decreased in the presence of ATD, suggesting that ATD may act both as an androgen receptor blocker and as an aromatization inhibitor. Competitive binding studies indicated that ATD competes in vitro for cytosol androgen receptors, thus substantiating the in vivo antiandrogenic effects of ATD"
Proof that ATD is not only an anti-androgen, but it competes with all of that 400-600% extra testosterone for binding to the androgen receptors. That means that any amount of estrogen in your body takes over and you get gyno.
(7) "No agonistic properties of ATD were observed either behaviorally or biochemically. Thus, an alternative explanation for the inhibitory effects of ATD on male sexual behavior is that ATD prevents T from binding to androgen receptors.
The negative ATD actions described above might not be experienced by everyone. Anabolic Xtreme does carry a 100% regular ATD based product Rebound XT™ that we stand behind. BUT if you are unsure how your body reacts to ATD or have any doubt, PCT™ is the product you should choose.
PCT™ is not a regular ATD based product…….it works!
Long ago researchers discovered that hydroxylation of ATD at carbon 17 results in a better compound that does not block all the androgen receptors in the whole body like regular ATD. The natural compound is a cousin of ATD made in the brain called 1,4,6-Androstatriene-17-ol-3-one. The only problem was that it was that it had very poor oral bioavailability. So Anabolic Xtreme took this poorly absorbed compound and attached a non liver toxic methyl group to the compound. By attaching the methyl group it makes the compound absorbed very well when taken orally (pill). We named this compound mATD.
1) Flesinoxan: a prosexual drug for male rats.
Eur J Pharmacol. 1997 Jul 2;330(1):1-9.
Eur J Pharmacol. 1997 Jul 2;330(1):1-9.
Related Articles, Links
Click here to read
Flesinoxan: a prosexual drug for male rats.
Haensel SM, Slob AK.
Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University and Dijkzigt Academic Hospital, Rotterdam, Netherlands. [email protected]
Two tests were carried out to compare the stimulatory (i.e., prosexual) effects of the 5-HT1A receptor agonists flesinoxan and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on sexual behavior in male Wistar rats. Two groups of rats were used: normal males and males with impaired masculine sexual behavior due to neonatal treatment with the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD). In Experiment 1, flesinoxan (0.3 and 1.0 mg/kg) stimulated ejaculation frequency and number of animals displaying this behavior, both in controls and ATD males. With 0.3 mg/kg flesinoxan ATD males did not differ from controls in ejaculation frequencies. There was a concomitant decrease in latency to first ejaculation. No 'premature' ejaculations (i.e., at first or second intromission) were observed. In Experiment 2, the effects of 0.4 mg/kg 8-OH-DPAT, 0.3, 1.0 and 3.0 mg/kg flesinoxan and saline were tested in two ejaculation series. 'Premature' ejaculations only occurred during first ejaculation series with 8-OH-DPAT in 8 of 10 controls and in 6 of 9 ATD males; it did not occur during flesinoxan treatment nor in the second ejaculation series with 8-OH-DPAT treatment. Thus, flesinoxan stimulates sexual behavior in control rats and in rats with impaired sexual behavior. Unlike 8-OH-DPAT flesinoxan does not render them into 'premature' ejaculators. Therefore, flesinoxan could be considered a prosexual drug for male rats.
(2) Endogenous reproductive hormones and nocturnal rhythms in partner preference and sexual behavior of ATD-treated male rats.
Neuroendocrinology. 1995 Oct;62(4):396-405.
Neuroendocrinology. 1995 Oct;62(4):396-405.
Related Articles, Links
Endogenous reproductive hormones and nocturnal rhythms in partner preference and sexual behavior of ATD-treated male rats.
Bakker J, van Ophemert J, Timmerman MA, de Jong FH, Slob AK.
Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands .
Male rats received subcutaneously silastic capsules, containing the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD), shortly after birth. Control males were given silastic capsules containing cholesterol. The capsules were removed at the age of 21 days. In adulthood, blood serum was collected early and late in the dark phase of the light/dark cycle (experiment I). Testosterone and luteinizing hormone and follicle stimulating hormone (FSH) fluctuated nocturnally, both in ATD and control males, with highest levels late in the dark phase. FSH levels were significantly higher in ATD males. Nocturnal levels of inhibin, a selective suppressor of pituitary FSH secretion, also fluctuated in both ATD and control males, with lowest levels late in the dark phase. In experiment II, ATD and control males were tested for partner preference behavior in a three-compartment box (choice: sexually active male vs. estrous female) early and late in the dark phase. When gonadally intact, ATD males, but not controls, showed a clear nocturnal rhythmicity in partner preference behavior and sexual behavior. Early in the dark phase, such ATD males preferred the vicinity of and interaction with a sexually active male. Late in the dark phase, this preference for the active male shifted to a preference for the estrous female. Control males preferred the estrous female. After castration and subsequent treatment with testosterone via silastic capsules, which ensured constant blood serum levels, ATD males continued to show their nocturnal rhythms in partner preference behavior and in sexual behavior. Thus, the underlying mechanism of the nocturnal rhythmicity phenomenon is an organizational effect of neonatal ATD treatment rather than an activational effect of fluctuating serum hormone levels.
(3) Increased number of vasopressin neurons in the suprachiasmatic nucleus (SCN) of 'bisexual' adult male rats following perinatal treatment with the aromatase blocker ATD.
Brain Res Dev Brain Res. 1995 Apr 18;85(2):273-9.
Related Articles, Links
Click here to read
Increased number of vasopressin neurons in the suprachiasmatic nucleus (SCN) of 'bisexual' adult male rats following perinatal treatment with the aromatase blocker ATD.
Swaab DF, Slob AK, Houtsmuller EJ, Brand T, Zhou JN.
Netherlands Institute for Brain Research, Graduate School Neurosciences Amsterdam .
In an earlier article an enlarged subpopulation of vasopressin containing neurons was found in the suprachiasmatic nucleus (SCN) of homosexual men as compared to heterosexuals. The present study investigates the possibility that the number of vasopressin neurons in the SCN and sexual partner preference behavior in male rats are both influenced by sex hormones during brain development. For this purpose, we studied groups of adult male rats that had been treated either prenatally or pre- and postnatally with the aromatase inhibitor ATD (1,4,6-androstatriene-3,17-dione) which blocks the aromatization of testosterone to estradiol. Rats treated with ATD in both pre- and postnatal periods showed 'bisexual' partner preference behavior and appeared to have 59% more vasopressin-expressing neurons in the SCN than the controls. The prenatally treated rats did not differ from the controls. This observation supports the hypothesis that the increased number of vasopressin neurons found earlier in the SCN of adult homosexual men might reflect differences that took place in the interaction between sex hormones and the brain early in development.
(4) Postweaning housing conditions and partner preference and sexual behavior of neonatally ATD-treated male rats.
Psychoneuroendocrinology. 1995;20(3):299-310.
Psychoneuroendocrinology. 1995;20(3):299-310.
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Postweaning housing conditions and partner preference and sexual behavior of neonatally ATD-treated male rats.
Bakker J, van Ophemert J, Slob AK.
Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands .
Male rats were neonatally treated with cholesterol or a substance that blocks the aromatization of testosterone to estradiol (1,4,6-androstatriene-3,17-dione: ATD). At weaning (21 days) they were either housed alone or in small groups (2-3 animals) and tested for partner preference behavior (PPB) in adulthood. Choice was between an estrous female and an active male (Part I) and between an estrous female and an ATD-male (Part II). Tests were carried out in a 3-compartment box. Social isolation did not have major effects on PPB except when sexual interaction with the stimulus animals was prevented (Part I). In this case, isolates (ATD and control) showed higher preference scores (PS) for the estrous female and spent less time in the empty middle compartment. When the choice was between an estrous female and an ATD-male, partner PS decreased in all males, most clearly in ATD-males. The latter animals spent more time with the stimulus ATD-male than they had done in previous PPB tests with the normal stimulus male. In contrast to partner preference behaviors, sexual behavior was clearly affected by social isolation. Isolates (ATD and control) displayed lower frequencies of mounts and intromissions. These effects persisted over consecutive tests. Ejaculation was not affected. In conclusion, the present results confirm earlier findings about the significance of neonatal endocrine conditions for the organization of adult PPB in male rats. The presence or absence of social conspecifics after weaning appears to have little influence on adult PPB.
(5) A semiautomated test apparatus for studying partner preference behavior in the rat.
Physiol Behav. 1994 Sep;56(3):597-601.
Physiol Behav. 1994 Sep;56(3):597-601.
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A semiautomated test apparatus for studying partner preference behavior in the rat.
Bakker J, van Ophemert J, Eijskoot F, Slob AK.
Department of Endocrinology and Reproduction, Erasmus University, Rotterdam, The Netherlands .
A semiautomated three-compartment box (3CB) for studying partner preference behavior of rats is described. This apparatus automatically records the rat's time spent in each compartment, as well as the locomotor activity (i.e., the number of visits an animal pays to each compartment). Software was developed for calculating partner preference scores. Behavioral testing in the semiautomated 3CB, which is a modification of an earlier version, is less time consuming and less laborious. Three 3CBs can be observed simultaneously by two trained observers, and the behavioral interactions of three experimental animals with the stimulus animals can be observed and scored by hand. The use of the new apparatus was validated by studying adult partner preference behavior of neonatally ATD-treated male rats. The collected data fully corroborate previous results, obtained in the earlier version of the 3CB, again revealing the behavioral bisexual nature of these ATD males. A new finding was the much higher locomotor activity of the ATD males compared to controls.
(6) SDN-POA volume, sexual behavior, and partner preference of male rats affected by perinatal treatment with ATD.
Physiol Behav. 1994 Sep;56(3):535-41.
Physiol Behav. 1994 Sep;56(3):535-41.
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SDN-POA volume, sexual behavior, and partner preference of male rats affected by perinatal treatment with ATD.
Houtsmuller EJ, Brand T, de Jonge FH, Joosten RN, van de Poll NE, Slob AK.
Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands .
The present study investigated 1) the importance of the aromatization process during the perinatal period for the development of the sexually dimorphic nucleus in the preoptic area of the hypothalamus (SDN-POA) of male rats, and 2) the relationship between SDN-POA volume and parameters of masculinization in male rats that were treated perinatally with the aromatase-inhibitor ATD. Males were treated with ATD either prenatally or pre- and neonatally, or with the vehicle. Masculine sexual behavior and partner preference were investigated in adulthood. Thereafter, animals were sacrificed and SDN-POA volume was measured. The SDN-POA volume was reduced in both the prenatally and the pre- and neonatally treated group, with a larger reduction in the latter than in the former group. Combined pre- and neonatal ATD treatment resulted in reduced frequency of mounts, intromissions, and ejaculations, as well as a reduced preference for a female over a male. The SDN-POA size was significantly and positively correlated with frequency of masculine sexual behavior, as well as preference for a female over a male.
(7) Effects of ATD on male sexual behavior and androgen receptor binding: a reexamination of the aromatization hypothesis.
Horm Behav. 1989 Mar;23(1):10-26.
Horm Behav. 1989 Mar;23(1):10-26.
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Effects of ATD on male sexual behavior and androgen receptor binding: a reexamination of the aromatization hypothesis.
Kaplan ME, McGinnis MY.
Department of Anatomy, Mount Sinai School of Medicine, CUNY, New York 10029.
The aromatization hypothesis asserts that testosterone (T) must be aromatized to estradiol (E2) to activate copulatory behavior in the male rat. In support of this hypothesis, the aromatization inhibitor, ATD, has been found to suppress male sexual behavior in T-treated rats. In our experiment, we first replicated this finding by peripherally injecting ATD (15 mg/day) or propylene glycol into T-treated (two 10-mm Silastic capsules) or control castrated male rats. In a second experiment, we bilaterally implanted either ATD-filled or blank cannulae into the medial preoptic area (MPOA) of either T-treated or control castrated male rats. With this more local distribution of ATD, a lesser decline in sexual behavior was found, suggesting that other brain areas are involved in the neurohormonal activation of copulatory behavior in the male rat. To determine whether in vivo ATD interacts with androgen or estrogen receptors, we conducted cell nuclear androgen and estrogen receptor binding assays of hypothalamus, preoptic area, amygdala, and septum following treatment with the combinations of systemic T alone. ATD plus T, ATD alone, and blank control. In all four brain areas binding of T to androgen receptors was significantly decreased in the presence of ATD, suggesting that ATD may act both as an androgen receptor blocker and as an aromatization inhibitor. Competitive binding studies indicated that ATD competes in vitro for cytosol androgen receptors, thus substantiating the in vivo antiandrogenic effects of ATD. Cell nuclear estrogen receptor binding was not significantly increased by exposure to T in the physiological range. No agonistic properties of ATD were observed either behaviorally or biochemically. Thus, an alternative explanation for the inhibitory effects of ATD on male sexual behavior is that ATD prevents T from binding to androgen receptors.
Differential effects of aromatase inhibition on luteinizing hormone secretion in intact and castrated male cynomolgus macaques.
J Clin Endocrinol Metab. 1993 Dec;77(6):1529-34.
J Clin Endocrinol Metab. 1993 Dec;77(6):1529-34.
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Differential effects of aromatase inhibition on luteinizing hormone secretion in intact and castrated male cynomolgus macaques.
Resko JA, Connolly PB, Roselli CE, Abdelgadir SE, Choate JV.
Department of Physiology, Oregon Health Sciences University, Portland 97201-3098.
To understand the role of central aromatization in feedback regulation of LH in nonhuman primates, we treated adult male cynomolgus monkeys with the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD). We measured LH, testosterone (T), and ATD in systemic sera of blood samples drawn on a diurnal schedule (0900 and 2100 h). Each animal was bled for 4 pretreatment days from a femoral catheter after which they were divided into the following treatment groups: castrated (Cx), n = 2; Cx + T, n = 6; Cx + T + ATD, n = 6; Cx + ATD, n = 3; and sham operated + ATD, n = 3. Silastic capsules or packets containing T or ATD, respectively, were placed sc between the scapulae at the time of Cx or sham treatment. In T-treated animals, T (20 micrograms/kg body weight) dissolved in propylene glycol was injected im at 2100 h to mimic the diurnal rise of T observed in nonhuman primates. Animals were bled for 2 weeks after which they were killed, and selected brain areas were analyzed for aromatase activity and cytosolic and nuclear androgen receptors. Animals treated with ATD had significantly reduced levels of aromatase activity in selected regions of the hypothalamus, preoptic area, and the amygdala (P < 0.05). Even though ATD inhibited brain aromatase activity, it did not prevent the negative feedback actions of T on LH secretion after Cx. In addition, ATD by itself inhibited LH secretion after Cx and activated brain androgen receptors. These latter effects of ATD seemed to have been mediated through a metabolite. In sham-operated intact males, ATD produced variable surges of LH that were accompanied by elevations of T in the systemic circulation. These differential effects of ATD in intact vs. castrated animals demonstrate the importance of selecting the proper model system to study LH control mechanisms. In the intact animal, aromatization seems to play a role in regulating LH secretion, but the postcastration rise of LH seems to be regulated differently.
Studies on aromatase inhibition with 4-androstene-3,6,17-trione: its 3 beta-reduction and time-dependent irreversible binding to aromatase with human placental microsomes.
Steroid Biochem. 1987 Sep;28(3):337-44.
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Studies on aromatase inhibition with 4-androstene-3,6,17-trione: its 3 beta-reduction and time-dependent irreversible binding to aromatase with human placental microsomes.
Numazawa M, Tsuji M, Mutsumi A.
Tohoku College of Pharmacy, Sendai, Japan.
The metabolism of 4-androstene-3,6,17-trione (AT), previously described as a suicide substrate for aromatase, and its irreversible binding to aromatase were studied by using human placental microsomes. AT was rapidly converted into 3 beta-reduced metabolite (3-OHAT) with an enzyme other than aromatase in the microsomes in the presence of NADPH under either aerobic or anaerobic conditions. The conversion was efficiently prevented by a steroid 5 alpha-reductase inhibitor. 3-OHAT was characterized as a competitive (Ki = 6.5 microM) and irreversible inhibitor of aromatase. Both 14C-labeled AT and 3-OHAT were demonstrated to be irreversibly bound to aromatase probably through a sulfur atom of the enzyme in time-dependent manners in the presence of NADPH, being accompanied with time-dependent losses of the enzyme activity. It was shown that the process of an apparent time-dependent loss of aromatase activity caused by AT even under conditions allowing its 3 beta-reduction should principally depend on the action of the parent inhibitor AT itself and not on that of the metabolite 3-OHAT.
Detection of androst-4-ene-3,6,17-trione (6-OXO) and its metabolites in urine by gas chromatography-mass spectrometry in relation to doping analysis.
Biomed Chromatogr. 2005 Nov;19(9):689-95.
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Detection of androst-4-ene-3,6,17-trione (6-OXO) and its metabolites in urine by gas chromatography-mass spectrometry in relation to doping analysis.
Van Thuyne W, Van Eenoo P, Mikulcikova P, Deventer K, Delbeke FT.
Doping Control Laboratory, Department of Clinical Biology, Microbiology and Immunology, Ghent University-UGent, Technologiepark 30, B-9052 Zwijnaarde, Belgium.
The metabolism and excretion of androst-4-ene-3,6,17-trione after administration of the 'nutritional' supplement 6-OXO was investigated by gas chromatography-mass spectrometry (GC-MS) in full-scan mode. The parent drug androst-4-ene-3,6,17-trione and androst-4-ene-6alpha,17beta-diol-3-one and androst-4-ene-6alpha-ol-3,17-dione were detected in the post-administration urine samples. Because androst-4-ene-3,6,17-trione is an anabolic steroid and an aromatase inhibitor, this substance is regarded as a doping agent. Hence, a selective and sensitive GC-MS method in selected ion monitoring mode for the detection of the TMS-enol-TMS-ether derivatives of these substances was developed and validated for doping control purposes. The limit of detection (LOD) of the investigated compounds ranged from 5 to 10 ng/mL. Using this method, the detection time for androst-4-ene-3,6,17-trione and androst-4-ene-6alpha,17beta-diol-3-one was 24 h, while androst-4-ene-6alpha-ol-3,17-dione could be detected up to 37 h after administration of the dose recommended by the manufacturer.
